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{{Short description|Group of diseases involving cell growth}} {{About|the group of diseases}} {{Pp-semi-indef}} {{pp-move}} {{Use dmy dates|date=February 2024}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox medical condition | name = Cancer | image = Tumor Mesothelioma2 legend.jpg | caption = A coronal [[CT scan]] showing a malignant [[mesothelioma]]<br />Legend: → [[tumor]] ←, ✱ central [[pleural effusion]], 1 & 3 [[lung]]s, 2 [[Vertebral column|spine]], 4 [[rib]]s, 5 [[aorta]], 6 [[spleen]], 7 & 8 [[kidney]]s, 9 [[liver]] | field = [[Oncology]] | synonyms = [[malignancy|Malignant]] [[neoplasm|tumor]], malignant [[neoplasm]] | pronounce = {{IPAc-en|audio=en-us-cancer.ogg|ˈ|k|æ|n|s|ər}} | symptoms = Lump, abnormal bleeding, prolonged cough, unexplained [[weight loss]], change in [[bowel movement]]s<ref name=NHS2012/> | complications = | onset = | duration = | causes = | risks = Exposure to [[carcinogen]]s, tobacco, [[obesity]], poor [[Diet (nutrition)|diet]], [[lack of physical activity]], excessive [[Alcohol (drug)|alcohol]], certain infections, genetics<ref name=WHO2018/><ref name=Enviro2008/> | diagnosis = | differential = | prevention = | treatment = [[Radiation therapy]], surgery, [[chemotherapy]], [[targeted therapy]]<ref name=WHO2018/><ref name=TCT2018/> | medication = | prognosis = Average [[five-year survival]] 66% (USA)<ref name=Seer2014/> | frequency = 24 million annually (2019)<ref name="kocarnik">{{cite journal | vauthors = Kocarnik JM, Compton K, Dean FE, Fu W, Gaw BL, Harvey JD, etal | title = Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life Years for 29 Cancer Groups From 2010 to 2019: A Systematic Analysis for the Global Burden of Disease Study 2019 | journal = JAMA Oncology | volume = 8 | issue = 3 | pages = 420–444 | date = March 2022 | pmid = 34967848 | pmc = 8719276 | doi = 10.1001/jamaoncol.2021.6987 |issn = 2374-2437}}</ref> | deaths = 10 million annually (2019)<ref name=kocarnik/> }} '''Cancer''' is a group of [[disease]]s involving [[Cell growth#Disorders|abnormal cell growth]] with the potential to [[Invasion (cancer)|invade]] or [[Metastasis|spread]] to other parts of the body.<ref name=WHO2018/><ref name=WhatIsCancerNCI/> These contrast with [[benign tumor]]s, which do not spread.<ref name=WhatIsCancerNCI/> Possible [[Signs and symptoms of cancer|signs and symptoms]] include a lump, abnormal bleeding, prolonged cough, unexplained weight loss, and a change in [[defecation|bowel movements]].<ref name=NHS2012>{{cite web |title=Cancer – Signs and symptoms |url=http://www.nhs.uk/Conditions/Cancer/Pages/Symptoms.aspx |website=NHS Choices |access-date=10 June 2014 |url-status=live |archive-url=https://web.archive.org/web/20140608104550/http://www.nhs.uk/Conditions/cancer/Pages/symptoms.aspx |archive-date=8 June 2014}}</ref> While these symptoms may indicate cancer, they can also have other causes.<ref name=NHS2012/> [[List of cancer types|Over 100 types]] of cancers affect humans.<ref name=WhatIsCancerNCI/> [[Tobacco use]] is the cause of about 22% of cancer deaths.<ref name=WHO2018>{{cite web |title=Cancer |url=https://www.who.int/en/news-room/fact-sheets/detail/cancer |website=World Health Organization |access-date=19 December 2018 |date=12 September 2018}}</ref> Another 10% are due to [[obesity]], poor [[Diet (nutrition)|diet]], [[sedentary lifestyle|lack of physical activity]] or [[Alcohol abuse|excessive alcohol consumption]].<ref name=WHO2018/><ref>{{cite web |title=Obesity and Cancer Risk |url=http://www.cancer.gov/about-cancer/causes-prevention/risk/obesity/obesity-fact-sheet#q3 |publisher=National Cancer Institute |access-date=4 July 2015 |date=3 January 2012 |url-status=live |archive-url=https://web.archive.org/web/20150704154440/http://www.cancer.gov/about-cancer/causes-prevention/risk/obesity/obesity-fact-sheet#q3 |archive-date=4 July 2015}}</ref><ref>{{cite journal | vauthors = Jayasekara H, MacInnis RJ, Room R, English DR | title = Long-Term Alcohol Consumption and Breast, Upper Aero-Digestive Tract and Colorectal Cancer Risk: A Systematic Review and Meta-Analysis | journal = Alcohol and Alcoholism | volume = 51 | issue = 3 | pages = 315–30 | date = May 2016 | pmid = 26400678 | doi = 10.1093/alcalc/agv110 | doi-access = free }}</ref> Other factors include certain infections, exposure to [[ionizing radiation]], and environmental pollutants.<ref name="Enviro2008">{{cite journal |vauthors=Anand P, Kunnumakkara AB, Sundaram C, Harikumar KB, Tharakan ST, Lai OS, Sung B, Aggarwal BB |date=September 2008 |title=Cancer is a preventable disease that requires major lifestyle changes |journal=Pharmaceutical Research |volume=25 |issue=9 |pages=2097–116 |doi=10.1007/s11095-008-9661-9 |pmc=2515569 |pmid=18626751}}{{Erratum|doi=10.1007/s11095-008-9690-4|pmid=18626751|checked=yes}}</ref> [[infectious causes of cancer|Infection]] with specific viruses, bacteria and parasites is an environmental factor causing approximately 16–18% of cancers worldwide.<ref>{{Cite journal|title=Global burden of cancer attributable to infections in 2018: a worldwide incidence analysis|first1=Catherine|last1=de Martel|first2=Damien|last2=Georges|first3=Freddie|last3=Bray|first4=Jacques|last4=Ferlay|first5=Gary M|last5=Clifford|date=15 February 2020|journal=The Lancet Global Health|volume=8|issue=2|pages=e180–e190|doi=10.1016/S2214-109X(19)30488-7|pmid=31862245 |doi-access=free}}</ref> These infectious agents include ''[[Helicobacter pylori]]'', [[hepatitis B]], [[hepatitis C]], [[human papillomavirus infection]], [[Epstein–Barr virus]], [[Human T-lymphotropic virus 1]], [[Kaposi's sarcoma-associated herpesvirus]] and [[Merkel cell polyomavirus]]. [[HIV|Human immunodeficiency virus]] (HIV) does not directly cause cancer but it causes immune deficiency that can magnify the risk due to other infections, sometimes up to several thousandfold (in the case of [[Kaposi's sarcoma]]). Importantly, vaccination against [[hepatitis B]] and [[human papillomavirus]] have been shown to nearly eliminate the risk of cancers caused by these viruses in persons successfully vaccinated prior to infection. These environmental factors act, at least partly, by changing the [[gene]]s of a cell.<ref name=WCR2014Scr/> Typically, many genetic changes are required before cancer develops.<ref name=WCR2014Scr/> Approximately 5–10% of cancers are due to inherited genetic defects.<ref name=ACS-heredity>{{cite web |publisher=[[American Cancer Society]] |title=Heredity and Cancer |access-date=22 July 2013 |url=http://www.cancer.org/cancer/cancercauses/geneticsandcancer/heredity-and-cancer |url-status=live |archive-url=https://web.archive.org/web/20130802043732/http://www.cancer.org/cancer/cancercauses/geneticsandcancer/heredity-and-cancer |archive-date=2 August 2013}}</ref> Cancer can be detected by certain signs and symptoms or screening tests.<ref name=WHO2018/> It is then typically further investigated by [[medical imaging]] and confirmed by [[biopsy]].<ref>{{cite web |title=How is cancer diagnosed? |url=http://www.cancer.org/treatment/understandingyourdiagnosis/examsandtestdescriptions/testingbiopsyandcytologyspecimensforcancer/testing-biopsy-and-cytology-specimens-for-cancer-how-is-cancer-diagnosed |website=American Cancer Society |date=29 January 2013 |access-date=10 June 2014 |url-status=live |archive-url=https://web.archive.org/web/20140714120018/http://www.cancer.org/treatment/understandingyourdiagnosis/examsandtestdescriptions/testingbiopsyandcytologyspecimensforcancer/testing-biopsy-and-cytology-specimens-for-cancer-how-is-cancer-diagnosed |archive-date=14 July 2014}}</ref> The risk of developing certain cancers can be reduced by not smoking, maintaining a healthy weight, limiting alcohol intake, eating plenty of vegetables, fruits, and [[whole grain]]s, [[vaccination]] against certain infectious diseases, limiting consumption of [[processed meat]] and [[red meat]], and limiting exposure to direct sunlight.<ref name=Kushi2012>{{cite journal |vauthors=Kushi LH, Doyle C, McCullough M, Rock CL, Demark-Wahnefried W, Bandera EV, Gapstur S, Patel AV, Andrews K, Gansler T |s2cid=2067308 |title=American Cancer Society Guidelines on nutrition and physical activity for cancer prevention: reducing the risk of cancer with healthy food choices and physical activity |journal= CA: A Cancer Journal for Clinicians |volume=62 |issue=1 |pages=30–67 |year=2012 |pmid=22237782 |doi=10.3322/caac.20140|doi-access=free }}</ref><ref>{{cite journal |vauthors=Parkin DM, Boyd L, Walker LC |title=16. The fraction of cancer attributable to lifestyle and environmental factors in the UK in 2010 |journal=British Journal of Cancer |volume=105 | issue = Suppl 2 |pages=S77–81 |date=December 2011 |pmid=22158327 |pmc=3252065 |doi=10.1038/bjc.2011.489}}</ref> Early detection through screening is useful for [[cervical cancer|cervical]] and [[colorectal cancer]].<ref name=WCR2014Scr>{{cite book |title=World Cancer Report 2014 |date=2014 |publisher=World Health Organization |isbn=978-92-832-0429-9 |url=http://www.searo.who.int/publications/bookstore/documents/9283204298/en/ |pages=Chapter 4.7 |archive-url=https://web.archive.org/web/20170712114430/http://www.searo.who.int/publications/bookstore/documents/9283204298/en/ |archive-date=12 July 2017 }}</ref> The benefits of [[breast cancer screening|screening for breast cancer]] are controversial.<ref name=WCR2014Scr/><ref name=Got2013>{{cite journal |vauthors=Gøtzsche PC, Jørgensen KJ |title=Screening for breast cancer with mammography |journal=The Cochrane Database of Systematic Reviews |volume=2013 |issue=6 |pages=CD001877 |date=June 2013 |pmid=23737396 |pmc=6464778 |doi=10.1002/14651858.CD001877.pub5}}</ref> Cancer is often treated with some combination of [[radiation therapy]], surgery, [[chemotherapy]] and [[targeted therapy]].<ref name=WHO2018/><ref name=TCT2018>{{cite web |url=https://www.cancer.gov/about-cancer/treatment/types/targeted-therapies/targeted-therapies-fact-sheet |title=Targeted Cancer Therapies |website=cancer.gov |publisher=National Cancer Institute |date=26 February 2018 |access-date=28 March 2018 }}</ref> More [[Personalized medicine|personalized therapies]] that harness a patient's immune system are emerging in the field of [[cancer immunotherapy]].<ref>{{cite journal |last1=Mishra |first1=AK |last2=Ali |first2=A |last3=Dutta |first3=S |last4=Banday |first4=S |last5=Malonia |first5=SK |title=Emerging Trends in Immunotherapy for Cancer |journal=Diseases |date=6 Sep 2022 |volume=10 |issue=3 |page=60 |doi=10.3390/diseases10030060 |doi-access=free |pmid=36135216 |pmc=9498256 }}</ref> Pain and symptom management are an important part of care.<ref name=WHO2018/> [[Palliative care]] is particularly important in people with advanced disease.<ref name=WHO2018/> The chance of survival depends on the type of cancer and [[cancer staging|extent of disease]] at the start of treatment.<ref name=WCR2014Scr/> In children under 15 at diagnosis, the [[five-year survival rate]] in the [[developed world]] is on average 80%.<ref name=WCR2014Peads>{{cite book |title=World Cancer Report 2014 |date=2014 |publisher=World Health Organization |isbn=978-92-832-0429-9 |url=http://www.searo.who.int/publications/bookstore/documents/9283204298/en/ |pages=Chapter 1.3 |archive-url=https://web.archive.org/web/20170712114430/http://www.searo.who.int/publications/bookstore/documents/9283204298/en/ |archive-date=12 July 2017 }}</ref> For cancer in the United States, the average five-year survival rate is 66% for all ages.<ref name=Seer2014>{{cite web |title=SEER Stat Fact Sheets: All Cancer Sites |publisher=National Cancer Institute |url=http://seer.cancer.gov/statfacts/html/all.html |access-date=18 June 2014 |url-status=live |archive-url=https://web.archive.org/web/20100926191037/http://seer.cancer.gov/statfacts/html/all.html |archive-date=26 September 2010}}</ref> In 2015, about 90.5 million people worldwide had cancer.<ref name=GBD2015Pre>{{cite journal |author=GBD |author-link=Global Burden of Disease Study |collaboration=Disease and Injury Incidence and Prevalence Collaborators |title=Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015 |journal= The Lancet |date=8 October 2016 |volume=388 |issue=10053 |pages=1545–1602 |pmid=27733282 |doi=10.1016/S0140-6736(16)31678-6 |pmc=5055577}}</ref> In 2019, annual cancer cases grew by 23.6 million people, and there were 10 million deaths worldwide, representing over the previous decade increases of 26% and 21%, respectively.<ref name=kocarnik /><ref>{{cite journal|doi=10.1146/annurev-cancerbio-030419-033612|doi-access=free|title=Metabolic Drivers in Hereditary Cancer Syndromes|year=2020| vauthors = Sciacovelli M, Schmidt C, Maher ER, Frezza C |journal=Annual Review of Cancer Biology|volume=4|pages=77–97}}</ref> The most common types of cancer in males are [[lung cancer]], [[prostate cancer]], [[colorectal cancer]], and [[stomach cancer]].<ref name=WCR2014>{{cite book |title=World Cancer Report 2014 |date=2014 |publisher=World Health Organization |isbn=978-92-832-0429-9 |pages=Chapter 1.1}}</ref><ref name="auto">{{cite journal | vauthors = Siegel RL, Miller KD, Wagle NS, Jemal A | title = Cancer statistics, 2023 | journal = CA | volume = 73 | issue = 1 | pages = 17–48 | date = January 2023 | pmid = 36633525 | doi = 10.3322/caac.21763 | doi-access = free }}</ref> In females, the most common types are [[breast cancer]], colorectal cancer, lung cancer, and [[cervical cancer]].<ref name=WCR2014Scr/><ref name=auto/> If [[skin cancer]] other than [[melanoma]] were included in total new cancer cases each year, it would account for around 40% of cases.<ref>{{cite journal | vauthors = Dubas LE, Ingraffea A | title = Nonmelanoma skin cancer | journal = Facial Plastic Surgery Clinics of North America | volume = 21 | issue = 1 | pages = 43–53 | date = February 2013 | pmid = 23369588 | doi = 10.1016/j.fsc.2012.10.003 }}</ref><ref name=Cak2012>{{cite journal | vauthors = Cakir BÖ, Adamson P, Cingi C | title = Epidemiology and economic burden of nonmelanoma skin cancer | journal = Facial Plastic Surgery Clinics of North America | volume = 20 | issue = 4 | pages = 419–422 | date = November 2012 | pmid = 23084294 | doi = 10.1016/j.fsc.2012.07.004 }}</ref> In children, [[acute lymphoblastic leukemia]] and [[brain tumors]] are most common, except in Africa, where [[non-Hodgkin lymphoma]] occurs more often.<ref name=WCR2014Peads/> In 2012, about 165,000 children under 15 years of age were diagnosed with cancer.<ref name=WCR2014/> The risk of cancer increases significantly with age, and many cancers occur more commonly in developed countries.<ref name=WCR2014Scr/> Rates are increasing as [[population ageing|more people live to an old age]] and as lifestyle changes occur in the developing world.<ref name=Epi11>{{cite journal | vauthors = Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D | title = Global cancer statistics | journal = CA | volume = 61 | issue = 2 | pages = 69–90 | date = February 2011 | pmid = 21296855 | doi = 10.3322/caac.20107 | s2cid = 30500384 | doi-access = free }}</ref> The global total economic costs of cancer were estimated at [[United States dollar|US$]]1.16 trillion (equivalent to ${{Inflation|US|1.16|2010|r=2}} trillion in {{Inflation/year|US}}) per year {{as of|2010|lc=y}}.<ref name=WCR2014Eco>{{cite book |title=World Report 2014 |date=2014 |publisher=World Health Organization |isbn=978-92-832-0429-9 |url=http://www.searo.who.int/publications/bookstore/documents/9283204298/en/ |pages=Chapter 6.7 |archive-url=https://web.archive.org/web/20170712114430/http://www.searo.who.int/publications/bookstore/documents/9283204298/en/ |archive-date=12 July 2017 }}</ref> [[File:En.Wikipedia-VideoWiki-Cancer.webm|thumb|thumbtime=0:32|upright=1.35|Video summary ([[Wikipedia:VideoWiki/Cancer|script]])]] {{TOC limit}} == Etymology and definitions == The word comes from the ancient Greek καρκίνος, meaning 'crab' and 'tumor'. Greek physicians [[Hippocrates]] and [[Galen]], among others, noted the similarity of crabs to some tumors with swollen veins. The word was introduced in English in the modern medical sense around 1600.<ref>{{Cite web |title=cancer |url=https://www.etymonline.com/word/cancer |url-status=live |archive-url=https://web.archive.org/web/20221107103233/https://www.etymonline.com/word/cancer |archive-date=7 November 2022 |website=www.etymonline.com}}</ref> Cancers comprise a large family of diseases that involve abnormal [[cell growth]] with the potential to invade or spread to other parts of the body.<ref name=WHO2018/><ref name=WhatIsCancerNCI/> They form a subset of [[neoplasm]]s. A neoplasm or tumor is a group of cells that have undergone unregulated growth and will often form a mass or lump, but may be distributed diffusely.<ref name=ACSglossary>{{cite web |title=Cancer Glossary |website=cancer.org |publisher=American Cancer Society |url=http://www.cancer.org/cancer/cancerglossary/index |access-date=11 September 2013 |url-status=live |archive-url=https://web.archive.org/web/20130901160014/http://www.cancer.org/cancer/cancerglossary/index |archive-date=1 September 2013}}</ref><ref name=NCIdefinition>{{cite web |title=What is cancer? |website=cancer.gov |publisher=National Cancer Institute |access-date=28 March 2018 |url=https://www.cancer.gov/about-cancer/understanding/what-is-cancer|date=17 September 2007}}</ref> All tumor cells show the [[The Hallmarks of Cancer|six hallmarks of cancer]]. These characteristics are required to produce a malignant tumor. They include:<ref name=Han2000/> * [[Cell growth]] and division absent the proper signals * Continuous growth and division even given contrary signals * Avoidance of [[apoptosis|programmed cell death]] * [[Biological immortality|Limitless number of cell divisions]] * Promoting [[angiogenesis|blood vessel construction]] * [[Invasion (cancer)|Invasion]] of tissue and formation of [[metastasis|metastases]]<ref name=Han2000/> The progression from normal cells to cells that can form a detectable mass to cancer involves multiple steps known as malignant progression.<ref name=Han2000>{{cite journal |vauthors=Hanahan D, Weinberg RA |s2cid=1478778 |title=The hallmarks of cancer |journal=Cell |volume=100 |issue=1 |pages=57–70 |date=January 2000 |pmid=10647931 |doi=10.1016/S0092-8674(00)81683-9 |author-link1=Douglas Hanahan |author-link2=Robert Weinberg (biologist)|doi-access=free }}</ref><ref name=Han2011>{{cite journal |vauthors=Hanahan D, Weinberg RA |title=Hallmarks of cancer: the next generation |journal=Cell |volume=144 |issue=5 |pages=646–74 |date=March 2011 |pmid=21376230 |doi=10.1016/j.cell.2011.02.013|doi-access=free }}</ref> == Signs and symptoms == {{Main|Signs and symptoms of cancer}} [[File:Symptoms of cancer metastasis.svg|thumb|upright=1.35|Symptoms of cancer [[metastasis]] depend on the location of the tumor.]] When cancer begins, it produces no symptoms. Signs and symptoms appear as the mass grows or [[ulcer (dermatology)|ulcerates]]. The findings that result depend on cancer's type and location. Few symptoms are [[non-specific symptom|specific]]. Many frequently occur in individuals who have other conditions. Cancer can be difficult to diagnose and can be considered a "[[the great imitator|great imitator]]".<ref name=Card10/> People may become anxious or depressed post-diagnosis. The risk of suicide in people with cancer is approximately double.<ref>{{cite journal |vauthors=Anguiano L, Mayer DK, Piven ML, Rosenstein D |s2cid=45874503 |title=A literature review of suicide in cancer patients |journal=Cancer Nursing |volume=35 |issue=4 |pages=E14–26 |date=July–August 2012 |pmid=21946906 |doi=10.1097/NCC.0b013e31822fc76c|doi-access=free }}</ref> === Local symptoms === Local symptoms may occur due to the mass of the tumor or its ulceration. For example, mass effects from lung cancer can block the [[bronchus]] resulting in cough or [[pneumonia]]; [[esophageal cancer]] can cause narrowing of the [[esophagus]], making it difficult or painful to swallow; and [[colorectal cancer]] may lead to narrowing or blockages in the [[bowel]], affecting bowel habits. Masses in breasts or testicles may produce observable lumps. [[ulcer (dermatology)|Ulceration]] can cause bleeding that can lead to symptoms such as [[hemoptysis|coughing up blood]] (lung cancer), [[anemia]] or [[Lower gastrointestinal bleeding|rectal bleeding]] (colon cancer), [[Hematuria|blood in the urine]] (bladder cancer), or [[abnormal vaginal bleeding]] (endometrial or cervical cancer). Although localized pain may occur in advanced cancer, the initial tumor is usually painless. Some cancers can cause a buildup of fluid within the chest or [[Ascites|abdomen]].<ref name="Card10">Holland Chp. 1</ref> === Systemic symptoms === Systemic symptoms may occur due to the body's response to the cancer. This may include fatigue, unintentional weight loss, or skin changes.<ref>{{cite book | vauthors = O'Dell M, Stubblefield M |title=Cancer rehabilitation principles and practice |year=2009 |publisher=Demos Medical |location=New York |isbn=978-1-933864-33-4 |page=983 |url={{google books |plainurl=y |id=_JaPlNYgXkEC |page=983}}}}</ref> Some cancers can cause a systemic inflammatory state that leads to ongoing muscle loss and weakness, known as [[cachexia]].<ref>{{cite journal | vauthors = Fearon K, Strasser F, Anker SD, Bosaeus I, Bruera E, Fainsinger RL, Jatoi A, Loprinzi C, MacDonald N, Mantovani G, Davis M, Muscaritoli M, Ottery F, Radbruch L, Ravasco P, Walsh D, Wilcock A, Kaasa S, Baracos VE | title = Definition and classification of cancer cachexia: an international consensus | journal = The Lancet. Oncology | volume = 12 | issue = 5 | pages = 489–95 | date = May 2011 | pmid = 21296615 | doi = 10.1016/S1470-2045(10)70218-7 }}</ref> Some cancers, such as [[Hodgkin's disease]], [[leukemia]]s, and [[Liver cancer|liver]] or [[kidney cancer]]s, can cause a persistent [[Fever of unknown origin|fever]].<ref name=Card10/> Shortness of breath, called [[Shortness of breath|dyspnea]], is a common symptom of cancer and its treatment. The causes of cancer-related dyspnea can include tumors in or around the lung, blocked airways, fluid in the lungs, pneumonia, or treatment reactions including an [[allergic response]].<ref>{{Cite web |title=Shortness of Breath {{!}} Cancer-related Side Effects |url=https://www.cancer.org/cancer/managing-cancer/side-effects/shortness-of-breath.html |access-date=10 October 2023 |website=www.cancer.org |language=en}}</ref> Treatment for dyspnea in patients with advanced cancer can include [[Fan (machine)|fans]], bilevel ventilation, [[acupressure]]/[[reflexology]] and multicomponent [[Non-pharmaceutical intervention|nonpharmacological interventions]].<ref>{{Cite book | vauthors = Dy SM, Gupta A, Waldfogel JM, Sharma R, Zhang A, Feliciano JL, Sedhom R, Day J, Gersten RA, Davidson PM, Bass EB |url=http://www.ncbi.nlm.nih.gov/books/NBK565137/ |title=Interventions for Breathlessness in Patients With Advanced Cancer |date=2020 |publisher=Agency for Healthcare Research and Quality (US) |series=AHRQ Comparative Effectiveness Reviews |location=Rockville (MD) |pmid=33289989}}</ref> Some systemic symptoms of cancer are caused by hormones or other molecules produced by the tumor, known as [[paraneoplastic syndromes]]. Common paraneoplastic syndromes include [[hypercalcemia]], which can cause [[altered mental state]], constipation and dehydration, or [[hyponatremia]], which can also cause altered mental status, vomiting, headaches, or seizures.<ref>{{cite journal | vauthors = Dimitriadis GK, Angelousi A, Weickert MO, Randeva HS, Kaltsas G, Grossman A | title = Paraneoplastic endocrine syndromes | journal = Endocrine-Related Cancer | volume = 24 | issue = 6 | pages = R173–R190 | date = June 2017 | pmid = 28341725 | doi = 10.1530/ERC-17-0036 | doi-access = free }}</ref> === Metastasis === {{Main|Metastasis}} [[Metastasis]] is the spread of cancer to other locations in the body. The dispersed tumors are called metastatic tumors, while the original is called the primary tumor. Almost all cancers can metastasize.<ref name=metastasis/> Most cancer deaths are due to cancer that has metastasized.<ref name="What is Metastasized Cancer">{{cite web |title=What is Metastasized Cancer? |url=http://www.nccn.com/component/content/article/54-cancer-basics/925-what-is-metastasized-cancer.html |website=National Comprehensive Cancer Network |access-date=18 July 2013 |archive-url=https://web.archive.org/web/20130707200430/http://www.nccn.com/component/content/article/54-cancer-basics/925-what-is-metastasized-cancer.html |archive-date=7 July 2013}}</ref> Metastasis is common in the late stages of cancer and it can occur via the blood or the [[lymphatic system]] or both. The typical steps in metastasis are: # Local [[Invasion (cancer)|invasion]] # [[Intravasation]] into the blood or lymph. # Circulation through the body. # [[Extravasation]] into the new tissue. # Proliferation # [[Angiogenesis]] Different types of cancers tend to metastasize to particular organs. Overall, the most common places for metastases to occur are the [[lung]]s, [[liver]], brain, and the [[bone]]s.<ref name="metastasis">{{cite web |url=https://www.cancer.gov/types/metastatic-cancer |title=Metastatic Cancer: Questions and Answers |access-date=28 March 2018|publisher=National Cancer Institute |date=12 May 2015}}</ref> While some cancers can be cured if detected early, metastatic cancer is more difficult to treat and control. Nevertheless, some recent treatments are demonstrating encouraging results.<ref>{{cite web |title=Why is cancer so hard to cure? |url=https://www.theage.com.au/national/why-is-cancer-so-hard-to-cure-20230626-p5djiw.html |access-date=17 July 2023 |website=The Age|date=15 July 2023 }}</ref> == Causes == {{Main|Causes of cancer}} [[File:GHS-pictogram-silhouette.svg|thumb|The GHS [[hazard symbol|Hazard pictogram]] for carcinogenic substances]] [[File:Share-of-cancer-deaths-attributed-to-tobacco.png|thumb|upright=1.6|Share of cancer deaths attributed to tobacco in 2016.<ref>{{cite web |title=Share of cancer deaths attributed to tobacco |url=https://ourworldindata.org/grapher/share-of-cancer-deaths-attributed-to-tobacco |website=Our World in Data |access-date=5 March 2020}}</ref>]] The majority of cancers, some 90–95% of cases, are due to genetic mutations from environmental and lifestyle factors.<ref name=Enviro2008/> The remaining 5–10% are due to [[Heredity|inherited genetics]].<ref name=Enviro2008/> ''[[Environment (biophysical)|Environmental]]'' refers to any cause that is not [[Heredity|inherited]], such as lifestyle, economic, and behavioral factors and not merely pollution.<ref name="isbn0-387-78192-7">{{cite book | vauthors = Manton K, Akushevich I, Kravchenko J |title=Cancer Mortality and Morbidity Patterns in the U.S. Population: An Interdisciplinary Approach |url={{google books |plainurl=y |id=fDIbuwtYPlAC}}|date=28 December 2008|publisher=Springer Science & Business Media|isbn=978-0-387-78193-8|quote = The term ''environment'' refers not only to air, water, and soil but also to substances and conditions at home and at the workplace, including diet, smoking, alcohol, drugs, exposure to chemicals, sunlight, ionizing radiation, electromagnetic fields, infectious agents, etc. Lifestyle, economic and behavioral factors are all aspects of our environment. }}</ref> Common environmental factors that contribute to cancer death include tobacco use (25–30%), diet and [[obesity]] (30–35%), infections (15–20%), [[radiation]] (both ionizing and non-ionizing, up to 10%), lack of [[physical exercise|physical activity]], and pollution.<ref name=Enviro2008/><ref>{{cite journal | vauthors = Islami F, Goding Sauer A, Miller KD, Siegel RL, Fedewa SA, Jacobs EJ, McCullough ML, Patel AV, Ma J, Soerjomataram I, Flanders WD, Brawley OW, Gapstur SM, Jemal A | title = Proportion and number of cancer cases and deaths attributable to potentially modifiable risk factors in the United States | journal = CA: A Cancer Journal for Clinicians | volume = 68 | issue = 1 | pages = 31–54 | date = January 2018 | pmid = 29160902 | doi = 10.3322/caac.21440 | doi-access = free }}</ref> Psychological stress does not appear to be a risk factor for the onset of cancer,<ref name=Cohen2019>{{cite journal | vauthors = Cohen S, Murphy ML, Prather AA | title = Ten Surprising Facts About Stressful Life Events and Disease Risk | journal = Annual Review of Psychology | volume = 70 | pages = 577–597 | date = January 2019 | pmid = 29949726 | pmc = 6996482 | doi = 10.1146/annurev-psych-010418-102857 | quote = the strongest conclusion derived from decades of research on stressors and cancer is that stressful events may be associated with decreased cancer survival but are probably not associated with disease incidence (Chida et al. 2008). }}</ref><ref name="pmid23393080">{{cite journal | vauthors = Heikkilä K, Nyberg ST, Theorell T, Fransson EI, Alfredsson L, Bjorner JB, Bonenfant S, Borritz M, Bouillon K, Burr H, Dragano N, Geuskens GA, Goldberg M, Hamer M, Hooftman WE, Houtman IL, Joensuu M, Knutsson A, Koskenvuo M, Koskinen A, Kouvonen A, Madsen IE, Magnusson Hanson LL, Marmot MG, Nielsen ML, Nordin M, Oksanen T, Pentti J, Salo P, Rugulies R, Steptoe A, Suominen S, Vahtera J, Virtanen M, Väänänen A, Westerholm P, Westerlund H, Zins M, Ferrie JE, Singh-Manoux A, Batty GD, Kivimäki M | title = Work stress and risk of cancer: meta-analysis of 5700 incident cancer events in 116,000 European men and women | journal = BMJ | volume = 346 | pages = f165 | date = February 2013 | pmid = 23393080 | pmc = 3567204 | doi = 10.1136/bmj.f165 }}</ref> though it may worsen outcomes in those who already have cancer.<ref name=Cohen2019/> Environmental or lifestyle factors that caused cancer to develop in an individual can be identified by analyzing mutational signatures from genomic sequencing of tumor DNA. For example, this can reveal if lung cancer was caused by tobacco smoke, if skin cancer was caused by UV radiation, or if [[Secondary malignant neoplasm|secondary cancers]] were caused by previous chemotherapy treatment.<ref name=cds>{{cite journal | vauthors = Steele CD, Pillay N, Alexandrov LB | title = An overview of mutational and copy number signatures in human cancer | journal = The Journal of Pathology | volume = 257 | issue = 4 | pages = 454–465 | date = July 2022 | pmid = 35420163 | pmc = 9324981 | doi = 10.1002/path.5912 }}</ref> Cancer is generally not a [[transmission (medicine)|transmissible disease]].<ref name=Tolar>{{cite journal |vauthors=Tolar J, Neglia JP |s2cid=34197973 |title=Transplacental and other routes of cancer transmission between individuals |journal=Journal of Pediatric Hematology/Oncology |volume=25 |issue=6 |pages=430–4 |date=June 2003 |pmid=12794519 |doi=10.1097/00043426-200306000-00002}}</ref> Exceptions include rare transmissions that occur with pregnancies and occasional [[Organ donation|organ donors]]. However, transmissible infectious diseases such as [[hepatitis B]], [[Epstein-Barr virus]], [[Human Papilloma Virus]] and [[HIV]], can contribute to the development of cancer.<ref>{{cite web |title=Hepatitis B virus (HBV) and hepatitis C virus (HCV) |url=https://www.cancer.org/cancer/risk-prevention/infections/infections-that-can-lead-to-cancer/viruses.html |website=American Cancer Society |access-date=15 February 2025}}</ref> === Chemicals === {{Further|Alcohol and cancer|Smoking and cancer}} [[File:Cancer smoking lung cancer correlation from NIH.svg|thumb|upright=1.35|The incidence of lung cancer is highly correlated with smoking.]] Exposure to particular substances have been linked to specific types of cancer. These substances are called ''[[carcinogen]]s''. [[Tobacco smoking|Tobacco smoke]], for example, causes 90% of lung cancer.<ref name="pmid9594919">{{cite journal |vauthors=Biesalski HK, Bueno de Mesquita B, Chesson A, Chytil F, Grimble R, Hermus RJ, Köhrle J, Lotan R, Norpoth K, Pastorino U, Thurnham D |title=European Consensus Statement on Lung Cancer: risk factors and prevention. Lung Cancer Panel |journal=CA: A Cancer Journal for Clinicians |volume=48 |issue=3 |pages=167–76; discussion 164–66 |year=1998 |pmid=9594919 |doi=10.3322/canjclin.48.3.167|s2cid=20891885 |doi-access=free }}</ref> Tobacco use can cause cancer throughout the body including in the mouth and throat, [[larynx]], [[esophagus]], stomach, bladder, kidney, cervix, colon/rectum, liver and [[pancreas]].<ref name="pmid12270001">{{cite journal |vauthors=Kuper H, Boffetta P, Adami HO |s2cid=6132726 |title=Tobacco use and cancer causation: association by tumour type |journal=Journal of Internal Medicine |volume=252 |issue=3 |pages=206–24 |date=September 2002 |pmid=12270001 |doi=10.1046/j.1365-2796.2002.01022.x|doi-access=free }}</ref><ref>{{Cite web |date=27 August 2019 |title=Cancer and Tobacco Use |url=https://www.cdc.gov/vitalsigns/cancerandtobacco/index.html |access-date=25 October 2023 |website=Centers for Disease Control and Prevention |language=en-us}}</ref> Tobacco smoke contains over fifty known carcinogens, including [[nitrosamine]]s and [[polycyclic aromatic hydrocarbon]]s.<ref name=Kuper/> Tobacco is responsible for about one in five cancer deaths worldwide<ref name="Kuper">{{cite journal |vauthors=Kuper H, Adami HO, Boffetta P |s2cid=9172672 |title=Tobacco use, cancer causation and public health impact |journal=Journal of Internal Medicine |volume=251 |issue=6 |pages=455–66 |date=June 2002 |pmid=12028500 |doi=10.1046/j.1365-2796.2002.00993.x|doi-access=free }}</ref> and about one in three in the developed world.<ref name="Sasco">{{cite journal |vauthors=Sasco AJ, Secretan MB, Straif K |title=Tobacco smoking and cancer: a brief review of recent epidemiological evidence |journal=Lung Cancer |volume=45 | issue = Suppl 2 |pages=S3–9 |date=August 2004 |pmid=15552776 |doi=10.1016/j.lungcan.2004.07.998}}</ref> Lung cancer death rates in the United States have mirrored [[tobacco smoking|smoking]] patterns, with increases in smoking followed by dramatic increases in lung cancer death rates and, more recently, decreases in smoking rates since the 1950s followed by decreases in lung cancer death rates in men since 1990.<ref name="pmid16998161">{{cite journal |vauthors=Thun MJ, Jemal A |title=How much of the decrease in cancer death rates in the United States is attributable to reductions in tobacco smoking? |journal=Tobacco Control |volume=15 |issue=5 |pages=345–47 |date=October 2006 |pmid=16998161 |pmc=2563648 |doi=10.1136/tc.2006.017749}}</ref><ref name="pmid18434333">{{cite journal |vauthors=Dubey S, Powell CA |title=Update in lung cancer 2007 |journal=American Journal of Respiratory and Critical Care Medicine |volume=177 |issue=9 |pages=941–46 |date=May 2008 |pmid=18434333 |pmc=2720127 |doi=10.1164/rccm.200801-107UP}}</ref> Alcohol increases the risk of cancer of the breast (in women), throat, liver, oesophagus, mouth, larynx, and colon.<ref>{{cite news |title=US top doctor calls for cancer warnings on alcohol |url=https://www.bbc.com/news/articles/cj90x3np0zpo |agency=BBC}}</ref> In Western Europe, 10% of cancers in males and 3% of cancers in females are attributed to alcohol exposure, especially liver and digestive tract cancers.<ref name="pmid21474525">{{cite journal |vauthors=Schütze M, Boeing H, Pischon T, Rehm J, Kehoe T, Gmel G, Olsen A, Tjønneland AM, Dahm CC, Overvad K, Clavel-Chapelon F, Boutron-Ruault MC, Trichopoulou A, Benetou V, Zylis D, Kaaks R, Rohrmann S, Palli D, Berrino F, Tumino R, Vineis P, Rodríguez L, Agudo A, Sánchez MJ, Dorronsoro M, Chirlaque MD, Barricarte A, Peeters PH, van Gils CH, Khaw KT, Wareham N, Allen NE, Key TJ, Boffetta P, Slimani N, Jenab M, Romaguera D, Wark PA, Riboli E, Bergmann MM |title=Alcohol attributable burden of incidence of cancer in eight European countries based on results from prospective cohort study |journal=BMJ |volume=342 |pages=d1584 |date=April 2011 |pmid=21474525 |pmc=3072472 |doi=10.1136/bmj.d1584}}</ref> Cancer from work-related substance exposures may cause between 2 and 20% of cases,<ref name="pmid18055160">{{cite journal |vauthors=Irigaray P, Newby JA, Clapp R, Hardell L, Howard V, Montagnier L, Epstein S, Belpomme D |title=Lifestyle-related factors and environmental agents causing cancer: an overview |journal=Biomedicine & Pharmacotherapy |volume=61 |issue=10 |pages=640–58 |date=December 2007 |pmid=18055160 |doi=10.1016/j.biopha.2007.10.006}}</ref> causing at least 200,000 deaths.<ref name="WHO_occup">{{cite press release |title=WHO calls for prevention of cancer through healthy workplaces |publisher=World Health Organization |date=27 April 2007 |url=https://www.who.int/mediacentre/news/notes/2007/np19/en/index.html |access-date=13 October 2007 |archive-url=https://web.archive.org/web/20071012202014/http://www.who.int/mediacentre/news/notes/2007/np19/en/index.html |archive-date=12 October 2007}}</ref> Cancers such as lung cancer and [[mesothelioma]] can come from inhaling tobacco smoke or [[asbestos]] fibers, or [[leukemia]] from exposure to [[benzene]].<ref name=WHO_occup/> Exposure to [[perfluorooctanoic acid]] (PFOA), which is predominantly used in the production of [[Polytetrafluoroethylene|Teflon]], is known to cause two kinds of cancer.<ref>{{cite web |url= https://www.scientificamerican.com/article/erin-brockovich-blasts-u-s-regulation-of-toxic-chemicals/ |title= Erin Brockovich Blasts U.S. Regulation of Toxic Chemicals |website= scientificamerican.com | publisher= Scientific American |date= 28 December 2020}}</ref><ref>{{cite news |title=Environmental Pollutant, PFOA, Associated with Increased Risk of Kidney Cancer |url=https://dceg.cancer.gov/news-events/news/2020/pfoa-kidney |work=[[National Cancer Institute]] |date=24 September 2020}}</ref> Chemotherapy drugs such as [[Platinum-based antineoplastic|platinum-based]] compounds are [[carcinogens]] that increase the risk of [[Secondary malignant neoplasm|secondary cancers]]<ref name=cds/> [[Azathioprine]], an [[immunosuppressive medication]], is a [[carcinogen]] that can cause [[primary tumors]] to develop.<ref name=cds/> === Diet and exercise === {{Main|Diet and cancer}} {{anchor|Diet}}Diet, [[Sedentary lifestyle|physical inactivity]], and [[obesity]] are related to up to 30–35% of cancer deaths.<ref name=Enviro2008/><ref name="Nutri06">{{cite journal |vauthors=Kushi LH, Byers T, Doyle C, Bandera EV, McCullough M, McTiernan A, Gansler T, Andrews KS, Thun MJ |s2cid=19823935 |title=American Cancer Society Guidelines on Nutrition and Physical Activity for cancer prevention: reducing the risk of cancer with healthy food choices and physical activity |journal=CA: A Cancer Journal for Clinicians |volume=56 |issue=5 |pages=254–81; quiz 313–14 |year=2006 |pmid=17005596 |doi=10.3322/canjclin.56.5.254|doi-access=free }}</ref> In the United States, excess body weight is associated with the development of many types of cancer and is a factor in 14–20% of cancer deaths.<ref name="Nutri06"/> A UK study including data on over 5 million people showed higher [[body mass index]] to be related to at least 10 types of cancer and responsible for around 12,000 cases each year in that country.<ref name="BhaskaranLancet">{{cite journal |vauthors=Bhaskaran K, Douglas I, Forbes H, dos-Santos-Silva I, Leon DA, Smeeth L |title=Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5·24 million UK adults |journal=Lancet |volume=384 |issue=9945 |pages=755–65 |date=August 2014 |pmid=25129328 |doi=10.1016/S0140-6736(14)60892-8 |pmc=4151483}}</ref> Physical inactivity is believed to contribute to cancer risk, not only through its effect on body weight but also through negative effects on the [[immune system]] and [[endocrine system]].<ref name="Nutri06"/> More than half of the effect from the diet is due to [[overnutrition]] (eating too much), rather than from eating too few vegetables or other healthful foods.{{citation needed|date=March 2024}} Some specific foods are linked to specific cancers. A high-salt diet is linked to [[gastric cancer]].<ref name=pmid18990005/> [[Aflatoxin B1]], a frequent food contaminant, causes liver cancer.<ref name=pmid18990005/> [[Betel nut]] chewing can cause oral cancer.<ref name="pmid18990005">{{cite journal |vauthors=Park S, Bae J, Nam BH, Yoo KY |title=Aetiology of cancer in Asia |journal=Asian Pacific Journal of Cancer Prevention |volume=9 |issue=3 |pages=371–80 |year=2008 |pmid=18990005 |url=http://www.apocpcontrol.org/page/popup_paper_file_view.php?pno=MzcxIFBhcmsucCZrY29kZT04MjI=&pgubun=i|archive-url=https://web.archive.org/web/20110904052252/http://www.apocpcontrol.org/page/popup_paper_file_view.php?pno=MzcxIFBhcmsucCZrY29kZT04MjI=&pgubun=i |archive-date=4 September 2011}}</ref> National differences in dietary practices may partly explain differences in cancer incidence. For example, [[gastric cancer]] is more common in Japan due to its high-salt diet<ref name="pmid19107449">{{Cite book |vauthors=Brenner H, Rothenbacher D, Arndt V |chapter=Epidemiology of Stomach Cancer |title=Cancer Epidemiology |volume=472 |chapter-url={{google books |plainurl=y |id=5v1JAQAAIAAJ |page=467}}|pages = 467–77 | year = 2009 | pmid = 19107449 | doi = 10.1007/978-1-60327-492-0_23 | isbn = 978-1-60327-491-3 | series = Methods in Molecular Biology |issue=5450 |pmc=2166976 }}</ref> while [[Colorectal cancer|colon cancer]] is more common in the United States. Immigrant cancer profiles mirror those of their new country, often within one generation.<ref name="pmid14278899">{{cite journal |vauthors=Buell P, Dunn JE |title=Cancer Mortality Among Japanese Issei and Nisei of California |journal=Cancer |volume=18 |issue=5 |pages=656–64 |date=May 1965 |pmid=14278899 |doi=10.1002/1097-0142(196505)18:5<656::AID-CNCR2820180515>3.0.CO;2-3|doi-access=free }}</ref> === Infection === {{Main|Infectious causes of cancer}} Worldwide, approximately 18% of cancer deaths are related to [[infectious disease]]s.<ref name=Enviro2008/> This proportion ranges from a high of 25% in Africa to less than 10% in the developed world.<ref name=Enviro2008/> Viruses<ref>{{cite journal | vauthors = Moore PS, Chang Y | title = Why do viruses cause cancer? Highlights of the first century of human tumour virology | journal = Nature Reviews. Cancer | volume = 10 | issue = 12 | pages = 878–889 | date = December 2010 | pmid = 21102637 | pmc = 3718018 | doi = 10.1038/nrc2961 | publisher = Springer Science and Business Media LLC }}</ref> are the usual infectious agents that cause cancer but [[bacteria]] and [[parasites]] may also play a role. [[Oncovirus]]es (viruses that can cause human cancer) include: * [[Human papillomavirus]] ([[cervical cancer]]), * [[Epstein–Barr virus]] ([[B-cell lymphoproliferative disease]] and [[nasopharyngeal carcinoma]]), * [[Kaposi's sarcoma herpesvirus]] ([[Kaposi's sarcoma]] and primary effusion lymphomas), * [[Hepatitis B]] and [[hepatitis C]] viruses ([[hepatocellular carcinoma]]) * [[Human T-cell leukemia virus-1]] (T-cell leukemias). * [[Merkel cell polyomavirus]] ([[Merkel cell carcinoma]]) Bacterial infection may also increase the risk of cancer, as seen in * ''[[Helicobacter pylori]]''-induced [[gastric carcinoma]].<ref name="Viral04">{{cite journal |vauthors=Pagano JS, Blaser M, Buendia MA, Damania B, Khalili K, Raab-Traub N, Roizman B |title=Infectious agents and cancer: criteria for a causal relation |journal=Seminars in Cancer Biology |volume=14 |issue=6 |pages=453–71 |date=December 2004 |pmid=15489139 |doi=10.1016/j.semcancer.2004.06.009 }}</ref><ref name="LjubojevicSkerlev2014">{{cite journal |vauthors=Ljubojevic S, Skerlev M |title=HPV-associated diseases |journal=Clinics in Dermatology |volume=32 |issue=2 |pages=227–34 |year=2014 |pmid=24559558 |doi=10.1016/j.clindermatol.2013.08.007}}</ref> * [[Colibactin]], a [[genotoxin]] associated with ''[[Escherichia coli]]'' infection ([[colorectal cancer]])<ref name=cds/> Parasitic infections associated with cancer include: * ''[[Schistosoma haematobium]]'' ([[Bladder cancer|squamous cell carcinoma of the bladder]]) * The [[liver fluke]]s, ''[[Opisthorchis viverrini]]'' and ''[[Clonorchis sinensis]]'' ([[cholangiocarcinoma]]).<ref name="pmid20539059">{{cite journal |vauthors=Samaras V, Rafailidis PI, Mourtzoukou EG, Peppas G, Falagas ME |title=Chronic bacterial and parasitic infections and cancer: a review |journal=Journal of Infection in Developing Countries |volume=4 |issue=5 |pages=267–81 |date=June 2010 |pmid=20539059 |doi=10.3855/jidc.819 |url=http://www.jidc.org/index.php/journal/article/download/20539059/387|url-status=live |archive-url=https://web.archive.org/web/20111004123357/http://www.jidc.org/index.php/journal/article/download/20539059/387 |archive-date=4 October 2011|doi-access=free }}</ref> === Radiation === {{Main|Radiation-induced cancer}} Radiation exposure such as [[ultraviolet radiation]] and radioactive material is a risk factor for cancer.<ref name=NCI2019Rad>{{cite web |title=Radiation |url=https://www.cancer.gov/about-cancer/causes-prevention/risk/radiation |publisher=National Cancer Institute |access-date=8 June 2019 |language=en |date=29 April 2015}}</ref><ref name=WHO2019>{{cite web |title=Sunlight |url=https://www.cancer.gov/about-cancer/causes-prevention/risk/sunlight |publisher=National Cancer Institute |access-date=8 June 2019 |language=en |date=29 April 2015}}</ref><ref>{{cite web |title=Cancer prevention |url=https://www.who.int/cancer/prevention/en/ |website=WHO |access-date=8 June 2019}}</ref> Many [[non-melanoma skin cancer]]s are due to ultraviolet radiation, mostly from sunlight.<ref name=WHO2019/> Sources of ionizing radiation include [[medical imaging]] and [[radon]] gas.<ref name=WHO2019/> Ionizing radiation is not a particularly strong [[mutagen]].<ref name=Little>{{cite book |veditors=Kufe DW, Pollock RE, Weichselbaum RR, Bast RC, Gansler TS, Holland JF, Frei E |title=Cancer medicine | vauthors = Little JB |chapter=Chapter 14: Ionizing Radiation |edition=6th |publisher=B.C. Decker |location=Hamilton, Ont |year=2000 |isbn=978-1-55009-113-7 |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK20793/ |url-status=live |archive-url=https://web.archive.org/web/20160102193148/http://www.ncbi.nlm.nih.gov/books/NBK20793/ |archive-date=2 January 2016}}</ref> Residential exposure to [[radon]] gas, for example, has similar cancer risks as [[passive smoking]]. Radiation is a more potent source of cancer when combined with other cancer-causing agents, such as radon plus tobacco smoke. Radiation can cause cancer in most parts of the body, in all animals and at any age. Children are twice as likely to develop radiation-induced leukemia as adults; radiation exposure before birth has ten times the effect.<ref name=Little/> Medical use of ionizing radiation is a small but growing source of radiation-induced cancers. Ionizing radiation may be used to treat other cancers, but this may, in some cases, induce a second form of cancer.<ref name=Little/> It is also used in some kinds of [[medical imaging]].<ref name="pmid18046031">{{cite journal |vauthors=Brenner DJ, Hall EJ |s2cid=2760372 |title=Computed tomography—an increasing source of radiation exposure |journal=The New England Journal of Medicine |volume=357 |issue=22 |pages=2277–84 |date=November 2007 |pmid=18046031 |doi=10.1056/NEJMra072149|url=https://repositorio.unal.edu.co/handle/unal/79492 }}</ref> Prolonged exposure to [[ultraviolet radiation]] from the [[sun]] can lead to [[melanoma]] and other skin malignancies.<ref name=Cleaver>{{cite book |vauthors=Cleaver JE, Mitchell DL |veditors=Bast RC, Kufe DW, Pollock RE |title=Holland-Frei Cancer Medicine |edition=5th |publisher=B.C. Decker |location=Hamilton, Ontario |year=2000 |chapter=15. Ultraviolet Radiation Carcinogenesis |isbn=978-1-55009-113-7 |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK20854/ |access-date=31 January 2011 | display-editors = etal |url-status=live |archive-url=https://web.archive.org/web/20150904102726/http://www.ncbi.nlm.nih.gov/books/NBK20854/ |archive-date=4 September 2015}}</ref> Clear evidence establishes ultraviolet radiation, especially the non-ionizing medium wave [[UVB]], as the cause of most non-melanoma [[skin cancer]]s, which are the most common forms of cancer in the world.<ref name=Cleaver/> Non-ionizing [[radio frequency]] radiation from mobile phones, [[electric power transmission]] and other similar sources has been described as a [[possible carcinogen]] by the [[World Health Organization]]'s [[International Agency for Research on Cancer]].<ref>{{cite web |title=IARC classifies radiofrequency electromagnetic fields as possibly carcinogenic to humans |url=http://www.iarc.fr/en/media-centre/pr/2011/pdfs/pr208_E.pdf |website=World Health Organization |url-status=live |archive-url=https://web.archive.org/web/20110601063650/http://www.iarc.fr/en/media-centre/pr/2011/pdfs/pr208_E.pdf |archive-date=1 June 2011}}</ref> Evidence, however, has not supported a concern.<ref name=NCI2019EF>{{cite web |title=Electromagnetic Fields and Cancer |url=https://www.cancer.gov/about-cancer/causes-prevention/risk/radiation/electromagnetic-fields-fact-sheet |publisher=National Cancer Institute |access-date=8 June 2019 |language=en |date=7 January 2019}}</ref><ref name=NCI2019Rad/> This includes that studies have not found a consistent link between mobile phone radiation and cancer risk.<ref>{{cite web |url=https://www.cancer.gov/about-cancer/causes-prevention/risk/radiation/cell-phones-fact-sheet |title=Cell Phones and Cancer Risk – National Cancer Institute |publisher=Cancer.gov |date=8 May 2013 |access-date=28 March 2018}}</ref> === Heredity === {{Main|Cancer syndrome}} The vast majority of cancers are non-hereditary (sporadic). [[Hereditary cancer]]s are primarily caused by an inherited genetic defect. Less than 0.3% of the population are carriers of a genetic mutation that has a large effect on cancer risk and these cause less than 3–10% of cancer.<ref name=Expert09>{{cite journal |vauthors=Roukos DH |s2cid=24746283 |title=Genome-wide association studies: how predictable is a person's cancer risk? |journal=Expert Review of Anticancer Therapy |volume=9 |issue=4 |pages=389–92 |date=April 2009 |pmid=19374592 |doi=10.1586/era.09.12|doi-access=free }}</ref> Some of these [[syndrome]]s include: certain inherited mutations in the genes ''[[BRCA1]]'' and ''[[BRCA2]]'' with a more than 75% risk of breast cancer and [[ovarian cancer]],<ref name=Expert09/> and [[hereditary nonpolyposis colorectal cancer]] (HNPCC or Lynch syndrome), which is present in about 3% of people with [[colorectal cancer]],<ref name=Lancet10>{{cite journal |vauthors=Cunningham D, Atkin W, Lenz HJ, Lynch HT, Minsky B, Nordlinger B, Starling N |s2cid=25299272 |title=Colorectal cancer |journal=Lancet |volume=375 |issue=9719 |pages=1030–47 |date=March 2010 |pmid=20304247 |doi=10.1016/S0140-6736(10)60353-4}}</ref> among others. Statistically for cancers causing most mortality, the [[relative risk]] of developing [[colorectal cancer]] when a [[first-degree relative]] (parent, sibling or child) has been diagnosed with it is about 2.<ref name="Kampman2007">{{cite journal | vauthors = Kampman E | title = A first-degree relative with colorectal cancer: what are we missing? | journal = Cancer Epidemiology, Biomarkers & Prevention | volume = 16 | issue = 1 | pages = 1–3 | date = January 2007 | pmid = 17220324 | doi = 10.1158/1055-9965.EPI-06-0984 | doi-access = free }}</ref> The corresponding relative risk is 1.5 for lung cancer,<ref name="CotéLiu2012">{{cite journal | vauthors = Coté ML, Liu M, Bonassi S, Neri M, Schwartz AG, Christiani DC, Spitz MR, Muscat JE, Rennert G, Aben KK, Andrew AS, Bencko V, Bickeböller H, Boffetta P, Brennan P, Brenner H, Duell EJ, Fabianova E, Field JK, Foretova L, Friis S, Harris CC, Holcatova I, Hong YC, Isla D, Janout V, Kiemeney LA, Kiyohara C, Lan Q, Lazarus P, Lissowska J, Le Marchand L, Mates D, Matsuo K, Mayordomo JI, McLaughlin JR, Morgenstern H, Müeller H, Orlow I, Park BJ, Pinchev M, Raji OY, Rennert HS, Rudnai P, Seow A, Stucker I, Szeszenia-Dabrowska N, Dawn Teare M, Tjønnelan A, Ugolini D, van der Heijden HF, Wichmann E, Wiencke JK, Woll PJ, Yang P, Zaridze D, Zhang ZF, Etzel CJ, Hung RJ | title = Increased risk of lung cancer in individuals with a family history of the disease: a pooled analysis from the International Lung Cancer Consortium | journal = European Journal of Cancer | volume = 48 | issue = 13 | pages = 1957–68 | date = September 2012 | pmid = 22436981 | doi = 10.1016/j.ejca.2012.01.038 | pmc = 3445438 }}</ref> and 1.9 for [[prostate cancer]].<ref name="Watkins BrunerMoore2003">{{cite journal | vauthors = Bruner DW, Moore D, Parlanti A, Dorgan J, Engstrom P | title = Relative risk of prostate cancer for men with affected relatives: systematic review and meta-analysis | journal = International Journal of Cancer | volume = 107 | issue = 5 | pages = 797–803 | date = December 2003 | pmid = 14566830 | doi = 10.1002/ijc.11466 | s2cid = 25591527 }}</ref> For breast cancer, the relative risk is 1.8 with a first-degree relative having developed it at 50 years of age or older, and 3.3 when the relative developed it when being younger than 50 years of age.<ref name="Singletary2003">{{cite journal | vauthors = Singletary SE | title = Rating the risk factors for breast cancer | journal = Annals of Surgery | volume = 237 | issue = 4 | pages = 474–482 | date = April 2003 | pmid = 12677142 | pmc = 1514477 | doi = 10.1097/01.SLA.0000059969.64262.87 }}</ref> Taller people have an increased risk of cancer because they have more cells than shorter people. Since height is genetically determined to a large extent, taller people have a heritable increase in cancer risk.<ref>{{cite journal | vauthors = Green J, Cairns BJ, Casabonne D, Wright FL, Reeves G, Beral V | title = Height and cancer incidence in the Million Women Study: prospective cohort, and meta-analysis of prospective studies of height and total cancer risk | journal = The Lancet. Oncology | volume = 12 | issue = 8 | pages = 785–94 | date = August 2011 | pmid = 21782509 | pmc = 3148429 | doi = 10.1016/S1470-2045(11)70154-1 }}</ref> === Physical agents === Some substances cause cancer primarily through their physical, rather than chemical, effects.<ref name=Maltoni>{{cite book |vauthors=Maltoni CF, Holland JF |veditors=Bast RC, Kufe DW, Pollock RE |title=Holland-Frei Cancer Medicine |edition=5th |publisher=B.C. Decker |location=Hamilton, Ontario |year=2000 |chapter=Chapter 16: Physical Carcinogens |isbn=978-1-55009-113-7 |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK20770/ |access-date=31 January 2011 | display-editors = etal |url-status=live |archive-url=https://web.archive.org/web/20150904102726/http://www.ncbi.nlm.nih.gov/books/NBK20770/ |archive-date=4 September 2015}}</ref> A prominent example of this is prolonged exposure to [[asbestos]], naturally occurring mineral fibers that are a major cause of [[mesothelioma]] (cancer of the [[serous membrane]]) usually the serous membrane surrounding the lungs.<ref name=Maltoni/> Other substances in this category, including both naturally occurring and synthetic asbestos-like fibers, such as [[wollastonite]], [[attapulgite]], [[glass wool]] and [[rock wool]], are believed to have similar effects.<ref name=Maltoni/> Non-fibrous particulate materials that cause cancer include powdered metallic [[cobalt]] and [[nickel]] and [[crystalline silica]] ([[quartz]], [[cristobalite]] and [[tridymite]]).<ref name=Maltoni/> Usually, physical carcinogens must get inside the body (such as through inhalation) and require years of exposure to produce cancer.<ref name=Maltoni/> Physical trauma resulting in cancer is relatively rare.<ref name=Gaeta>{{cite book | vauthors = Gaeta JF | veditors = Bast RC, Kufe DW, Pollock RE |title=Holland-Frei Cancer Medicine |edition=5th |publisher=B.C. Decker |location=Hamilton, Ontario |year=2000 |chapter=Chapter 17: Trauma and Inflammation |isbn=978-1-55009-113-7 |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK20784/ |access-date=27 January 2011|display-editors=etal |url-status=live |archive-url=https://web.archive.org/web/20150904102726/http://www.ncbi.nlm.nih.gov/books/NBK20784/ |archive-date=4 September 2015}}</ref> Claims that breaking bones resulted in bone cancer, for example, have not been proven.<ref name=Gaeta/> Similarly, physical trauma is not accepted as a cause for cervical cancer, breast cancer or brain cancer.<ref name=Gaeta/> One accepted source is frequent, long-term application of hot objects to the body. It is possible that repeated burns on the same part of the body, such as those produced by [[kanger]] and kairo heaters (charcoal [[hand warmer]]s), may produce skin cancer, especially if carcinogenic chemicals are also present.<ref name=Gaeta/> Frequent consumption of scalding hot tea may produce esophageal cancer.<ref name=Gaeta/> Generally, it is believed that cancer arises, or a pre-existing cancer is encouraged, during the process of healing, rather than directly by the trauma.<ref name=Gaeta/> However, repeated injuries to the same tissues might promote excessive cell proliferation, which could then increase the odds of a cancerous mutation.{{citation needed|date=March 2024}} Chronic [[inflammation]] has been hypothesized to directly cause mutation.<ref name=Gaeta/><ref name="ColottaAllavena2009">{{cite journal |vauthors=Colotta F, Allavena P, Sica A, Garlanda C, Mantovani A |title=Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability |journal=Carcinogenesis |volume=30 |issue=7 |pages=1073–81 |date=July 2009 |pmid=19468060 |doi=10.1093/carcin/bgp127 |type=review|doi-access=free }}</ref> Inflammation can contribute to proliferation, survival, angiogenesis and migration of cancer cells by influencing the [[tumor microenvironment]].<ref>{{cite journal |vauthors=Ungefroren H, Sebens S, Seidl D, Lehnert H, Hass R |title=Interaction of tumor cells with the microenvironment |journal=Cell Communication and Signaling |volume=9 |page=18 |date=September 2011 |pmid=21914164 |doi=10.1186/1478-811X-9-18 |number=18 |pmc=3180438 |doi-access=free }}</ref><ref>{{cite journal |vauthors=Mantovani A |title=Molecular pathways linking inflammation and cancer |journal=Current Molecular Medicine |volume=10 |issue=4 |pages=369–73 |date=June 2010 |pmid=20455855 |doi=10.2174/156652410791316968 |type=review}}</ref> [[Oncogene]]s build up an inflammatory pro-tumorigenic microenvironment.<ref>{{cite journal |vauthors=Borrello MG, Degl'Innocenti D, Pierotti MA |title=Inflammation and cancer: the oncogene-driven connection |journal=Cancer Letters |volume=267 |issue=2 |pages=262–70 |date=August 2008 |pmid=18502035 |doi=10.1016/j.canlet.2008.03.060 |type=review}}</ref> === Hormones === [[Hormone]]s also play a role in the development of cancer by promoting [[cell growth|cell proliferation]].<ref name=Henderson>{{cite book |vauthors=Henderson BE, Bernstein L, Ross RK |veditors=Bast RC, Kufe DW, Pollock RE |title=Holland-Frei Cancer Medicine |edition=5th |publisher=B.C. Decker |location=Hamilton, Ontario |year=2000 |chapter=Chapter 13: Hormones and the Etiology of Cancer |isbn=978-1-55009-113-7 |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK20759/ |access-date=27 January 2011 | display-editors = etal |url-status=live |archive-url=https://web.archive.org/web/20170910174411/https://www.ncbi.nlm.nih.gov/books/NBK20759/ |archive-date=10 September 2017}}</ref> [[Insulin-like growth factor]]s and their binding proteins play a key role in cancer cell proliferation, differentiation and [[apoptosis]], suggesting possible involvement in carcinogenesis.<ref>{{cite journal |vauthors=Rowlands MA, Gunnell D, Harris R, Vatten LJ, Holly JM, Martin RM |title=Circulating insulin-like growth factor peptides and prostate cancer risk: a systematic review and meta-analysis |journal=International Journal of Cancer |volume=124 |issue=10 |pages=2416–29 |date=May 2009 |pmid=19142965 |pmc=2743036 |doi=10.1002/ijc.24202}}</ref> Hormones are important agents in sex-related cancers, such as cancer of the breast, [[endometrium]], prostate, ovary and [[testicle|testis]] and also of [[thyroid cancer]] and [[bone cancer]].<ref name=Henderson/> For example, the daughters of women who have breast cancer have significantly higher levels of [[estrogen]] and [[progesterone]] than the daughters of women without breast cancer. These higher hormone levels may explain their higher risk of breast cancer, even in the absence of a breast-cancer gene.<ref name=Henderson/> Similarly, men of African ancestry have significantly higher levels of [[testosterone]] than men of European ancestry and have a correspondingly higher level of prostate cancer.<ref name=Henderson/> Men of Asian ancestry, with the lowest levels of testosterone-activating [[androstanediol glucuronide]], have the lowest levels of prostate cancer.<ref name=Henderson/> Other factors are relevant: obese people have higher levels of some hormones associated with cancer and a higher rate of those cancers.<ref name=Henderson/> Women who take [[Hormone replacement therapy (menopause)|hormone replacement therapy]] have a higher risk of developing cancers associated with those hormones.<ref name=Henderson/> On the other hand, people who exercise far more than average have lower levels of these hormones and lower risk of cancer.<ref name=Henderson/> [[Osteosarcoma]] may be promoted by [[growth hormone]]s.<ref name=Henderson/> Some treatments and prevention approaches leverage this cause by artificially reducing hormone levels and thus discouraging hormone-sensitive cancers.<ref name=Henderson/> === Autoimmune diseases === There is an association between [[celiac disease]] and an increased risk of all cancers. People with untreated celiac disease have a higher risk, but this risk decreases with time after diagnosis and strict treatment. This may be due to the adoption of a [[gluten-free diet]], which seems to have a protective role against the development of malignancy in people with celiac disease. However, the delay in diagnosis and initiation of a gluten-free diet seems to increase the risk of malignancies.<ref name="pmid26402826">{{cite journal |vauthors=Han Y, Chen W, Li P, Ye J |title=Association Between Coeliac Disease and Risk of Any Malignancy and Gastrointestinal Malignancy: A Meta-Analysis |journal=Medicine |volume=94 |issue=38 |pages=e1612 |date=September 2015 |pmid=26402826 |pmc=4635766 |doi=10.1097/MD.0000000000001612}}</ref> Rates of gastrointestinal cancers are increased in people with [[Crohn's disease]] and [[ulcerative colitis]], due to chronic inflammation. [[immunotherapy|Immunomodulators]] and [[biological therapy for inflammatory bowel disease|biologic agents]] used to treat these diseases may promote the development of extra-intestinal malignancies.<ref>{{cite journal |vauthors=Axelrad JE, Lichtiger S, Yajnik V |title=Inflammatory bowel disease and cancer: The role of inflammation, immunosuppression, and cancer treatment |journal=World Journal of Gastroenterology |volume=22 |issue=20 |pages=4794–801 |date=May 2016 |pmid=27239106 |pmc=4873872 |doi=10.3748/wjg.v22.i20.4794 |doi-access=free }}</ref> == Pathophysiology == {{Main|Carcinogenesis}} === Genetics === {{Main|Oncogenomics}} [[File:Cancer requires multiple mutations from NIHen.png|thumb|upright|Cancers are caused by a series of mutations. Each mutation alters the behavior of the cell somewhat.]] Cancer is fundamentally a disease of tissue growth regulation. For a normal cell to [[malignant transformation|transform]] into a cancer cell, the [[gene]]s that regulate cell growth and differentiation must be altered.<ref name="pmid18234754">{{cite journal |vauthors=Croce CM |s2cid=8813076 |title=Oncogenes and cancer |journal=The New England Journal of Medicine |volume=358 |issue=5 |pages=502–11 |date=January 2008 |pmid=18234754 |doi=10.1056/NEJMra072367}}</ref> The affected genes are divided into two broad categories. [[Oncogene]]s are genes that promote cell growth and reproduction. [[Tumor suppressor gene]]s are genes that inhibit cell division and survival. Malignant transformation can occur through the formation of novel oncogenes, the inappropriate over-expression of normal oncogenes, or by the under-expression or disabling of tumor suppressor genes. Typically, changes in multiple genes are required to transform a normal cell into a cancer cell.<ref name="pmid11905807">{{cite journal |vauthors=Knudson AG |s2cid=20201610 |title=Two genetic hits (more or less) to cancer |journal=Nature Reviews. Cancer |volume=1 |issue=2 |pages=157–62 |date=November 2001 |pmid=11905807 |doi=10.1038/35101031}}</ref> Genetic changes can occur at different levels and by different mechanisms. The gain or loss of an entire [[chromosome]] can occur through errors in [[mitosis]]. More common are [[mutation]]s, which are changes in the [[nucleotide]] sequence of genomic DNA. Large-scale mutations involve the deletion or gain of a portion of a chromosome. [[Gene duplication|Genomic amplification]] occurs when a cell gains copies (often 20 or more) of a small chromosomal locus, usually containing one or more oncogenes and adjacent genetic material. [[Chromosomal translocation|Translocation]] occurs when two separate chromosomal regions become abnormally fused, often at a characteristic location. A well-known example of this is the [[Philadelphia chromosome]], or translocation of chromosomes 9 and 22, which occurs in [[chronic myelogenous leukemia]] and results in production of the [[BCR (gene)|BCR]]-[[aBL (gene)|abl]] [[fusion protein]], an oncogenic [[tyrosine kinase]]. Small-scale mutations include point mutations, deletions, and insertions, which may occur in the [[promoter (genetics)|promoter]] region of a gene and affect its [[gene expression|expression]], or may occur in the gene's [[coding sequence]] and alter the function or stability of its [[protein]] product. Disruption of a single gene may also result from [[provirus|integration of genomic material]] from a [[DNA virus]] or [[retrovirus]], leading to the expression of ''viral'' oncogenes in the affected cell and its descendants. Replication of the data contained within the DNA of living cells will [[probability|probabilistically]] result in some errors (mutations). Complex error correction and prevention are built into the process and safeguard the cell against cancer. If a significant error occurs, the damaged cell can self-destruct through programmed cell death, termed [[apoptosis]]. If the error control processes fail, then the mutations will survive and be passed along to [[cell division|daughter cells]]. Some environments make errors more likely to arise and propagate. Such environments can include the presence of disruptive substances called [[carcinogen]]s, repeated physical injury, heat, ionising radiation, or [[hypoxia (medical)|hypoxia]].<ref>{{cite journal |vauthors=Nelson DA, Tan TT, Rabson AB, Anderson D, Degenhardt K, White E |title=Hypoxia and defective apoptosis drive genomic instability and tumorigenesis |journal=Genes & Development |volume=18 |issue=17 |pages=2095–107 |date=September 2004 |pmid=15314031 |pmc=515288 |doi=10.1101/gad.1204904}}</ref> The errors that cause cancer are self-amplifying and compounding, for example: * A mutation in the error-correcting machinery of a cell might cause that cell and its children to accumulate errors more rapidly. * A further mutation in an oncogene might cause the cell to reproduce more rapidly and more frequently than its normal counterparts. * A further mutation may cause the loss of a tumor suppressor gene, disrupting the apoptosis signaling pathway and immortalizing the cell. * A further mutation in the signaling machinery of the cell might send error-causing signals to nearby cells. The transformation of a normal cell into cancer is akin to a [[chain reaction]] caused by initial errors, which compound into more severe errors, each progressively allowing the cell to escape more controls that limit normal tissue growth. This rebellion-like scenario is an undesirable [[survival of the fittest]], where the driving forces of [[evolution]] work against the body's design and enforcement of order. Once cancer has begun to develop, this ongoing process, termed ''[[Somatic evolution in cancer|clonal evolution]]'', drives progression towards more invasive [[cancer staging|stages]].<ref name="pmid17109012">{{cite journal |vauthors=Merlo LM, Pepper JW, Reid BJ, Maley CC |s2cid=8040576 |title=Cancer as an evolutionary and ecological process |journal=Nature Reviews. Cancer |volume=6 |issue=12 |pages=924–35 |date=December 2006 |pmid=17109012 |doi=10.1038/nrc2013}}</ref> Clonal evolution leads to intra-[[tumour heterogeneity]] (cancer cells with heterogeneous mutations) that complicates designing effective treatment strategies and requires an [[Evolutionary therapy|evolutionary approach to designing treatment]]. Characteristic abilities developed by cancers are divided into categories, specifically evasion of apoptosis, self-sufficiency in growth signals, insensitivity to anti-growth signals, sustained angiogenesis, limitless replicative potential, metastasis, reprogramming of energy metabolism and evasion of immune destruction.<ref name=Han2000/><ref name=Han2011/> === Epigenetics === {{Main|Cancer epigenetics}} [[File:Diagram Damage to Cancer Wiki 300dpi.svg|thumb|upright=1.35|The central role of DNA damage and epigenetic defects in DNA repair genes in carcinogenesis]] The classical view of cancer is a set of diseases driven by progressive [[Genetics|genetic]] [[abnormalities]] that include mutations in tumor-suppressor genes and [[oncogene]]s, and in [[chromosome|chromosomal]] abnormalities. A role for [[Epigenetics|epigenetic alterations]] was identified in the early 21st century.<ref>{{cite journal |vauthors=Baylin SB, Ohm JE |s2cid=2514545 |title=Epigenetic gene silencing in cancer – a mechanism for early oncogenic pathway addiction? |journal=Nature Reviews. Cancer |volume=6 |issue=2 |pages=107–16 |date=February 2006 |pmid=16491070 |doi=10.1038/nrc1799}}</ref> [[Epigenetics|Epigenetic]] alterations are functionally relevant modifications to the genome that do not change the nucleotide sequence. Examples of such modifications are changes in [[DNA methylation]] (hypermethylation and hypomethylation), [[histone modification]]<ref>{{cite journal |vauthors=Kanwal R, Gupta S |title=Epigenetic modifications in cancer |journal=Clinical Genetics |volume=81 |issue=4 |pages=303–11 |date=April 2012 |pmid=22082348 |pmc=3590802 |doi=10.1111/j.1399-0004.2011.01809.x}}</ref> and changes in chromosomal architecture (caused by inappropriate expression of proteins such as [[HMGA2]] or [[HMGA1]]).<ref>{{cite journal |vauthors=Baldassarre G, Battista S, Belletti B, Thakur S, Pentimalli F, Trapasso F, Fedele M, Pierantoni G, Croce CM, Fusco A |title=Negative regulation of BRCA1 gene expression by HMGA1 proteins accounts for the reduced BRCA1 protein levels in sporadic breast carcinoma |journal=Molecular and Cellular Biology |volume=23 |issue=7 |pages=2225–38 |date=April 2003 |pmid=12640109 |pmc=150734 |doi=10.1128/MCB.23.7.2225-2238.2003}}/</ref> Each of these alterations regulates gene expression without altering the underlying [[DNA sequence]]. These changes may remain through [[cell division]]s, endure for multiple generations, and can be considered as equivalent to mutations. Epigenetic alterations occur frequently in cancers. As an example, one study listed protein coding genes that were frequently altered in their [[methylation]] in association with colon cancer. These included 147 hypermethylated and 27 hypomethylated genes. Of the hypermethylated genes, 10 were hypermethylated in 100% of colon cancers and many others were hypermethylated in more than 50% of colon cancers.<ref name="Sch">{{cite journal |vauthors=Schnekenburger M, Diederich M |title=Epigenetics Offer New Horizons for Colorectal Cancer Prevention |journal=Current Colorectal Cancer Reports |volume=8 |issue=1 |pages=66–81 |date=March 2012 |pmid=22389639 |pmc=3277709 |doi=10.1007/s11888-011-0116-z}}</ref> While epigenetic alterations are found in cancers, the epigenetic alterations in DNA repair genes, causing reduced expression of DNA repair proteins, may be of particular importance. Such alterations may occur early in the progression to cancer and are a possible cause of the [[Genome instability|genetic]] instability characteristic of cancers.<ref>{{cite journal |vauthors=Jacinto FV, Esteller M |title=Mutator pathways unleashed by epigenetic silencing in human cancer |journal=Mutagenesis |volume=22 |issue=4 |pages=247–53 |date=July 2007 |pmid=17412712 |doi=10.1093/mutage/gem009|doi-access=free }}</ref><ref>{{cite journal |vauthors=Lahtz C, Pfeifer GP |title=Epigenetic changes of DNA repair genes in cancer |journal=Journal of Molecular Cell Biology |volume=3 |issue=1 |pages=51–8 |date=February 2011 |pmid=21278452 |pmc=3030973 |doi=10.1093/jmcb/mjq053}}</ref><ref>{{cite journal |vauthors=Bernstein C, Nfonsam V, Prasad AR, Bernstein H |title=Epigenetic field defects in progression to cancer |journal=World Journal of Gastrointestinal Oncology |volume=5 |issue=3 |pages=43–49 |date=March 2013 |pmid=23671730 |pmc=3648662 |doi=10.4251/wjgo.v5.i3.43 |doi-access=free }}</ref> Reduced expression of DNA repair genes disrupts DNA repair. This is shown in the figure at the 4th level from the top. (In the figure, red wording indicates the central role of DNA damage and defects in DNA repair in the progression to cancer.) When DNA repair is deficient DNA damage remains in cells at a higher than usual level (5th level) and causes increased frequencies of mutation and/or epimutation (6th level). Mutation rates increase substantially in cells defective in [[DNA mismatch repair]]<ref>{{cite journal |vauthors=Narayanan L, Fritzell JA, Baker SM, Liskay RM, Glazer PM |title=Elevated levels of mutation in multiple tissues of mice deficient in the DNA mismatch repair gene Pms2 |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=94 |issue=7 |pages=3122–27 |date=April 1997 |pmid=9096356 |pmc=20332 |doi=10.1073/pnas.94.7.3122|bibcode=1997PNAS...94.3122N |doi-access=free }}</ref><ref>{{cite journal |vauthors=Hegan DC, Narayanan L, Jirik FR, Edelmann W, Liskay RM, Glazer PM |title=Differing patterns of genetic instability in mice deficient in the mismatch repair genes Pms2, Mlh1, Msh2, Msh3 and Msh6 |journal=Carcinogenesis |volume=27 |issue=12 |pages=2402–08 |date=December 2006 |pmid=16728433 |pmc=2612936 |doi=10.1093/carcin/bgl079}}</ref> or in [[homologous recombination]]al repair (HRR).<ref>{{cite journal |vauthors=Tutt AN, van Oostrom CT, Ross GM, van Steeg H, Ashworth A |title=Disruption of Brca2 increases the spontaneous mutation rate in vivo: synergism with ionizing radiation |journal=EMBO Reports |volume=3 |issue=3 |pages=255–60 |date=March 2002 |pmid=11850397 |pmc=1084010 |doi=10.1093/embo-reports/kvf037}}</ref> Chromosomal rearrangements and aneuploidy also increase in HRR defective cells.<ref>{{cite journal |vauthors=German J |title=Bloom's syndrome. I. Genetical and clinical observations in the first twenty-seven patients |journal=American Journal of Human Genetics |volume=21 |issue=2 |pages=196–227 |date=March 1969 |pmid=5770175 |pmc=1706430}}</ref> Higher levels of DNA damage cause increased mutation (right side of figure) and increased epimutation. During repair of DNA double strand breaks, or repair of other DNA damage, incompletely cleared repair sites can cause epigenetic gene silencing.<ref>{{cite journal |vauthors=O'Hagan HM, Mohammad HP, Baylin SB |title=Double strand breaks can initiate gene silencing and SIRT1-dependent onset of DNA methylation in an exogenous promoter CpG island |journal=PLOS Genetics |volume=4 |issue=8 |pages=e1000155 |date=August 2008 |pmid=18704159 |pmc=2491723 |doi=10.1371/journal.pgen.1000155 | veditors = Lee JT |doi-access=free }}</ref><ref>{{cite journal |vauthors=Cuozzo C, Porcellini A, Angrisano T, Morano A, Lee B, Di Pardo A, Messina S, Iuliano R, Fusco A, Santillo MR, Muller MT, Chiariotti L, Gottesman ME, Avvedimento EV |title=DNA damage, homology-directed repair, and DNA methylation |journal=PLOS Genetics |volume=3 |issue=7 |pages=e110 |date=July 2007 |pmid=17616978 |pmc=1913100 |doi=10.1371/journal.pgen.0030110 |doi-access=free }}</ref> Deficient expression of DNA repair proteins due to an inherited mutation can increase cancer risks. Individuals with an inherited impairment in any of 34 DNA repair genes (see article [[DNA repair-deficiency disorder]]) have increased cancer risk, with some defects ensuring a 100% lifetime chance of cancer (e.g. p53 mutations).<ref>{{cite journal |vauthors=Malkin D |title=Li-fraumeni syndrome |journal=Genes & Cancer |volume=2 |issue=4 |pages=475–84 |date=April 2011 |pmid=21779515 |pmc=3135649 |doi=10.1177/1947601911413466}}</ref> Germline DNA repair mutations are noted on the figure's left side. However, such [[germline]] mutations (which cause highly penetrant cancer syndromes) are the cause of only about 1 percent of cancers.<ref>{{cite journal |vauthors=Fearon ER |title=Human cancer syndromes: clues to the origin and nature of cancer |journal=Science |volume=278 |issue=5340 |pages=1043–50 |date=November 1997 |pmid=9353177 |doi=10.1126/science.278.5340.1043|bibcode=1997Sci...278.1043F }}</ref> In sporadic cancers, deficiencies in DNA repair are occasionally caused by a mutation in a DNA repair gene but are much more frequently caused by epigenetic alterations that reduce or silence expression of DNA repair genes. This is indicated in the figure at the 3rd level. Many studies of heavy metal-induced carcinogenesis show that such heavy metals cause a reduction in expression of DNA repair enzymes, some through epigenetic mechanisms. DNA repair inhibition is proposed to be a predominant mechanism in heavy metal-induced carcinogenicity. In addition, frequent epigenetic alterations of the DNA sequences code for small RNAs called [[microRNA]]s (or miRNAs). miRNAs do not code for proteins, but can "target" protein-coding genes and reduce their expression. Cancers usually arise from an assemblage of mutations and epimutations that confer a selective advantage leading to clonal expansion (see [[Neoplasm#Field defects in progression to cancer|Field defects in progression to cancer]]). Mutations, however, may not be as frequent in cancers as epigenetic alterations. An average cancer of the breast or colon can have about 60 to 70 protein-altering mutations, of which about three or four may be "driver" mutations and the remaining ones may be "passenger" mutations.<ref>{{cite journal |vauthors=Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA, Kinzler KW |title=Cancer genome landscapes |journal=Science |volume=339 |issue=6127 |pages=1546–58 |date=March 2013 |pmid=23539594 |pmc=3749880 |doi=10.1126/science.1235122|bibcode=2013Sci...339.1546V }}</ref> === Metastasis === {{Main|Metastasis}} [[Metastasis]] is the spread of cancer to other locations in the body. The dispersed tumors are called metastatic tumors, while the original is called the primary tumor. Almost all cancers can metastasize.<ref name=metastasis/> Most cancer deaths are due to cancer that has metastasized.<ref name="What is Metastasized Cancer"/> Metastasis is common in the late stages of cancer and it can occur via the blood or the [[lymphatic system]] or both. The typical steps in metastasis are local [[Invasion (cancer)|invasion]], [[intravasation]] into the blood or lymph, circulation through the body, [[extravasation]] into the new tissue, proliferation and [[angiogenesis]]. Different types of cancers tend to metastasize to particular organs, but overall the most common places for metastases to occur are the [[lung]]s, [[liver]], brain and the [[bone]]s.<ref name=metastasis/> === Metabolism === {{Main|Tumor metabolome}} Normal cells typically generate only about 30% of energy from [[glycolysis]],<ref name="pmid23226794">{{cite journal | vauthors = Zheng J | title=Energy metabolism of cancer: Glycolysis versus oxidative phosphorylation (Review) | journal=[[Oncology Letters]] | volume=4 | issue=6 | pages=1151–1157 | year=2012 | doi = 10.3892/ol.2012.928 | pmc= 3506713 | pmid=23226794}}</ref> whereas most cancers rely on glycolysis for energy production ([[Warburg effect (oncology)|Warburg effect]]).<ref name="pmid20181022">{{cite journal | vauthors = Seyfried TN, Shelton LM | title=Cancer as a metabolic disease | journal=Nutrition & Metabolism | volume=7 | page=7 | year=2010 | doi = 10.1186/1743-7075-7-7 | pmc= 2845135 | pmid=20181022 | doi-access=free }}</ref><ref name="pmid31781842">{{cite journal | vauthors = Weiss JM | title=The promise and peril of targeting cell metabolism for cancer therapy | journal=[[Cancer Immunology, Immunotherapy]] | volume=69 | issue=2 | pages=255–261 | year=2020 | doi = 10.1007/s00262-019-02432-7 | pmc= 7004869 | pmid=31781842}}</ref> But a minority of cancer types rely on [[oxidative phosphorylation]] as the primary energy source, including [[lymphoma]], [[leukemia]], and [[endometrial cancer]].<ref name="pmid33028168">{{cite journal | vauthors = Farhadi P, Yarani R, Dokaneheifard S, Mansouri K | title = The emerging role of targeting cancer metabolism for cancer therapy | journal = [[Tumor Biology]] | volume = 42 | issue = 10 | page = 1010428320965284 | year = 2020 | doi = 10.1177/1010428320965284 | pmid = 33028168 | s2cid = 222214285 | doi-access = free }}</ref> Even in these cases, however, the use of glycolysis as an energy source rarely exceeds 60%.<ref name=pmid23226794/> A few cancers use [[glutamine]] as the major energy source, partly because it provides nitrogen required for [[nucleotide]] (DNA, RNA) synthesis.<ref name="pmid26771115">{{cite journal | vauthors=Pavlova NN, Thompson CB | title=The Emerging Hallmarks of Cancer Metabolism | journal=[[Cell Metabolism]] | volume=23 | issue=1 | pages=27–47 | year=2016 | doi = 10.1016/j.cmet.2015.12.006 | pmc= 4715268 | pmid=26771115}}</ref> [[Cancer stem cell]]s often use oxidative phosphorylation or glutamine as a primary energy source.<ref name="pmid32670883">{{cite journal | vauthors=Yadav UP, Singh T, Kumar P, Mehta K | title=Metabolic Adaptations in Cancer Stem Cells | journal=[[Frontiers in Oncology]] | volume=10 | page=1010 | year=2020 | doi = 10.3389/fonc.2020.01010 | pmc= 7330710 | pmid=32670883| doi-access=free }}</ref> == Diagnosis == {{Refimprove-section|date=January 2025}}[[File:Thorax pa peripheres Bronchialcarcinom li OF markiert.jpg|thumb|upright=1.35|Chest [[Projectional radiography|X-ray]] showing lung cancer in the left lung]] Most cancers are initially recognized either because of the appearance of signs or symptoms or through [[cancer screening|screening]].<ref>{{Cite web |title=Cancer Screening Guidelines {{!}} Detecting Cancer Early |url=https://www.cancer.org/healthy/find-cancer-early/american-cancer-society-guidelines-for-the-early-detection-of-cancer.html |access-date=24 May 2022 |publisher=American Cancer Society|date=14 March 2022 |language=en}}</ref> Neither of these leads to a definitive diagnosis, which requires the examination of a tissue sample by a [[anatomical pathology|pathologist]].<ref name="HollandFrei6">{{cite book | chapter=Role of the Surgical Pathologist in the Diagnosis and Management of the Cancer Patient | vauthors = Connolly JL, Schnitt SJ, Wang HH, Longtine JA, Dvorak A, Dvorak HF |author6-link=Harold F. Dvorak | veditors = Holland JF, Frei E, Kufe DW |editor1-link=James F. Holland |editor2-link=Emil Frei |title=Holland-Frei Cancer Medicine |edition=6 |location=Hamilton (ON) |publisher=BC Decker |year=2003 |isbn=978-1-55009-213-4 |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK13237/ |url=https://www.ncbi.nlm.nih.gov/books/NBK12354/}}</ref> People with suspected cancer are investigated with [[medical test]]s. These commonly include [[blood test]]s, [[Projectional radiography|X-rays]], ([[contrast CT|contrast]]) [[CT scan]]s and [[endoscopy]]. The tissue [[medical diagnosis|diagnosis]] from the biopsy indicates the type of cell that is proliferating, its [[histological grade]], genetic abnormalities and other features. Together, this information is useful to evaluate the [[prognosis]] and to choose the best treatment. [[Cytogenetics]] and [[immunohistochemistry]] are other types of tissue tests. These tests provide information about molecular changes (such as [[mutation]]s, [[fusion gene]]s and numerical [[chromosome]] changes) and may thus also indicate the prognosis and best treatment. Cancer diagnosis can cause psychological distress and psychosocial interventions, such as talking therapy, may help people with this.<ref>{{cite journal | vauthors = Galway K, Black A, Cantwell M, Cardwell CR, Mills M, Donnelly M | title = Psychosocial interventions to improve quality of life and emotional wellbeing for recently diagnosed cancer patients | journal = The Cochrane Database of Systematic Reviews | volume = 11 | pages = CD007064 | date = November 2012 | issue = 11 | pmid = 23152241 | pmc = 6457819 | doi = 10.1002/14651858.cd007064.pub2 }}</ref> Some people choose to disclose the diagnosis widely; others prefer to keep the information private, especially shortly after the diagnosis, or to disclose it only partially or to selected people.<ref>{{Cite journal | vauthors = Pearson C |date=10 January 2024 |title=Why Some People Keep Serious Illnesses Private |url=https://www.nytimes.com/2024/01/10/well/family/hidden-cancer-lloyd-austin.html |journal=The New York Times}}</ref> == Classification == {{further|List of cancer types|List of oncology-related terms}}{{Refimprove section|date=January 2025}}[[File:Histopathology of adenocarcinoma.png|thumb|240px|A large proportion of cancers are [[adenocarcinoma]]s, with typical [[histopathology]] features shown, although they vary substantially from case to case.]] Cancers are classified by the [[List of distinct cell types in the adult human body|type of cell]] that the tumor cells resemble and is therefore presumed to be the origin of the tumor. These types include: * [[Carcinoma]]: Cancers derived from [[epithelium|epithelial]] cells. This group includes many of the most common cancers and include nearly all those in the [[breast cancer|breast]], [[prostate cancer|prostate]], [[lung cancer|lung]], [[pancreas]] and [[Colorectal cancer|colon]]. Most of these are of the [[adenocarcinoma]] type, which means that the cancer has [[gland]]-like differentiation. * [[Sarcoma]]: Cancers arising from [[connective tissue]] (i.e. [[bone]], [[cartilage]], fat, [[nerve]]), each of which develops from cells originating in [[mesenchyme|mesenchymal]] cells outside the [[bone marrow]]. * [[Lymphoma]] and [[leukemia]]: These two classes arise from hematopoietic (blood-forming) cells that leave the marrow and tend to mature in the [[lymph node]]s and blood, respectively.<ref>{{cite book | vauthors = Varricchio C | title = A cancer source book for nurses |publisher=Jones and Bartlett Publishers |location=Boston |year=2004 |page=229 |isbn=978-0-7637-3276-9 |url={{google books |plainurl=y |id=jkqdgZcF9qcC |page=229}}}}</ref> * [[Germ cell tumor]]: Cancers derived from [[pluripotent]] cells, most often presenting in the [[testicular cancer|testicle]] or the [[ovarian cancer|ovary]] ([[seminoma]] and [[dysgerminoma]], respectively). * [[Blastoma]]: Cancers derived from immature "precursor" cells or embryonic tissue. Cancers are usually named using ''-carcinoma'', ''-sarcoma'' or ''-blastoma'' as a suffix, with the Latin or Greek word for the [[organ (anatomy)|organ]] or tissue of origin as the root. For example, cancers of the liver [[parenchyma]] arising from malignant epithelial cells is called ''[[hepatocellular carcinoma|hepatocarcinoma]]'', while a malignancy arising from primitive liver precursor cells is called a [[hepatoblastoma]] and a cancer arising from fat cells is called a ''[[liposarcoma]]''. For some common cancers, the English organ name is used. For example, the most common type of breast cancer is called ''[[mammary ductal carcinoma|ductal carcinoma of the breast]]''. Here, the adjective ''ductal'' refers to the appearance of cancer under the microscope, which suggests that it has originated in the milk ducts. [[Benign tumor]]s (which are not cancers) are named using ''-oma'' as a suffix with the organ name as the root. For example, a benign tumor of smooth muscle cells is called a ''[[leiomyoma]]'' (the common name of this frequently occurring benign tumor in the uterus is ''[[uterine fibroid|fibroid]]''). Confusingly, some types of cancer use the ''-noma'' suffix, examples including [[melanoma]] and [[seminoma]]. Some types of cancer are named for the size and shape of the cells under a microscope, such as giant cell carcinoma, [[spindle cell carcinoma]] and [[small-cell carcinoma]]. <gallery> File:Breast cancer gross appearance.jpg|An invasive [[ductal carcinoma]] of the breast (pale area at the center) surrounded by spikes of whitish scar tissue and yellow fatty tissue File:Colon cancer 2.jpg|An invasive [[colorectal carcinoma]] (top center) in a [[colectomy]] specimen File:Lung cancer.jpg|A [[squamous-cell carcinoma]] (the whitish tumor) near the [[bronchi]] in a lung specimen File:BreastCancer.jpg|A large invasive [[Mammary ductal carcinoma|ductal carcinoma]] in a [[mastectomy]] specimen File:Histopathology of squamous-cell carcinoma.png|[[Squamous cell carcinoma]] with typical histopathology features. File:Histopathology of small cell carcinoma, annotated.png|Histopathology of [[small-cell carcinoma]], with typical findings.<ref>Image by Mikael Häggström, MD. Source for findings: {{cite web|url=https://www.pathologyoutlines.com/topic/lungtumorsmallcell.html|title=Lung – Small cell carcinoma|website=Pathology Outlines| vauthors = Underwood CI, Glass C }} Last author update: 20 September 2022</ref> </gallery> == Prevention == {{Main|Cancer prevention}} [[File:Global deaths from cancers attributable to risk factors in 2019 by sex and SDI.jpg|thumb|upright=1.15 |Global deaths from cancers attributable to risk factors in 2019 by sex and {{tooltip|Socio-demographic Index|a measure of a location's socio-demographic development that takes into account average income per person, educational attainment, and total fertility rate}}.<ref name="10.1016/S0140-6736(22)01438-6"/>]] [[File:Cancer DALYs attributable to 11 Level 2 risk factors globally in 2019.jpg|thumb|upright=1.15|Cancer [[DALY]]s attributable to 11 Level 2 risk factors globally in 2019.<ref name="10.1016/S0140-6736(22)01438-6"/>]] Cancer prevention is defined as active measures to decrease cancer risk.<ref>{{cite web |title=Cancer prevention: 7 steps to reduce your risk |publisher=[[Mayo Clinic]] |url=http://www.mayoclinic.com/health/cancer-prevention/CA00024 |date=27 September 2008 |access-date=30 January 2010 |url-status=live |archive-url=https://web.archive.org/web/20100208082208/http://www.mayoclinic.com/health/cancer-prevention/CA00024 |archive-date=8 February 2010}}</ref> The vast majority of cancer cases are due to environmental risk factors. Many of these environmental factors are controllable lifestyle choices. Thus, cancer is generally preventable.<ref name=Danaei>{{cite journal |vauthors=Danaei G, Vander Hoorn S, Lopez AD, Murray CJ, Ezzati M |s2cid=17354479 |title=Causes of cancer in the world: comparative risk assessment of nine behavioural and environmental risk factors |journal=Lancet |volume=366 |issue=9499 |pages=1784–93 |date=November 2005 |pmid=16298215 |doi=10.1016/S0140-6736(05)67725-2|doi-access=free }}</ref> Between 70% and 90% of common cancers are due to environmental factors and therefore potentially preventable.<ref>{{cite journal |vauthors=Wu S, Powers S, Zhu W, Hannun YA |title=Substantial contribution of extrinsic risk factors to cancer development |journal=Nature |volume=529 |issue=7584 |pages=43–7 |date=January 2016 |pmid=26675728 |pmc=4836858 |doi=10.1038/nature16166 |bibcode=2016Natur.529...43W}}</ref> Greater than 30% of cancer deaths could be prevented by avoiding risk factors including: tobacco, [[overweight|excess weight]]/[[obesity]], poor diet, [[physical inactivity]], [[alcohol (drug)|alcohol]], [[sexually transmitted infection]]s and air pollution.<ref name="Cancer Cancer">{{cite web |url=https://www.who.int/mediacentre/factsheets/fs297/en/ |title=Cancer |website=World Health Organization |access-date=9 January 2011 |url-status=live |archive-url=https://web.archive.org/web/20101229092321/http://www.who.int/mediacentre/factsheets/fs297/en/ |archive-date=29 December 2010}}</ref> Further, poverty could be considered as an indirect risk factor in human cancers.<ref>{{cite journal | vauthors = Heidary F, Rahimi A, Gharebaghi R | title = Poverty as a risk factor in human cancers | journal = Iranian Journal of Public Health | volume = 42 | issue = 3 | pages = 341–343 | date = 2013 | pmid = 23641414 | pmc = 3633807 }}</ref> Not all environmental causes are controllable, such as naturally occurring [[background radiation]] and cancers caused through hereditary [[genetic disorders]] and thus are not preventable via personal behavior. In 2019, ~44% of all cancer deaths – or ~4.5 M deaths or ~105 million lost [[disability-adjusted life year]]s – were [[List of causes of death by rate#Underlying causes|due to known clearly preventable risk factors]]<!--(causal-contributing factors)-->, led by [[smoking]], [[Health effects of alcohol|alcohol use]] and [[obesity|high BMI]], according to a [[Global Burden of Disease Study|GBD]] [[Systematic review|systematic analysis]].<ref name="10.1016/S0140-6736(22)01438-6">{{cite journal | vauthors = Tran KB, Lang JJ, Compton K, Xu R, Acheson AR, Henrikson HJ, etal | title = The global burden of cancer attributable to risk factors, 2010-19: a systematic analysis for the Global Burden of Disease Study 2019 | language = English | journal = Lancet | volume = 400 | issue = 10352 | pages = 563–591 | date = August 2022 | pmid = 35988567 | pmc = 9395583 | doi = 10.1016/S0140-6736(22)01438-6 | doi-access = free }}</ref> === Dietary === {{Main|Diet and cancer}} While many dietary recommendations have been proposed to reduce cancer risks, the evidence to support them is not definitive.<ref name=Kushi2012/><ref name=Diet11>{{cite journal |vauthors=Wicki A, Hagmann J |title=Diet and cancer |journal=[[Swiss Medical Weekly]] |volume=141 |pages=w13250 |date=September 2011 |pmid=21904992 |doi=10.4414/smw.2011.13250|doi-access=free }}</ref> The primary dietary factors that increase risk are [[obesity]] and alcohol consumption. Diets low in fruits and vegetables and high in red meat have been implicated but reviews and meta-analyses do not come to a consistent conclusion.<ref name="pmid22202045">{{cite journal |vauthors=Cappellani A, Di Vita M, Zanghi A, Cavallaro A, Piccolo G, Veroux M, Berretta M, Malaguarnera M, Canzonieri V, Lo Menzo E |title=Diet, obesity and breast cancer: an update |journal=Frontiers in Bioscience |volume=4 |pages=90–108 |date=January 2012 |issue=1 |pmid=22202045 |doi=10.2741/253}}</ref><ref name="pmid21119663">{{cite journal |vauthors=Key TJ |title=Fruit and vegetables and cancer risk |journal=British Journal of Cancer |volume=104 |issue=1 |pages=6–11 |date=January 2011 |pmid=21119663 |pmc=3039795 |doi=10.1038/sj.bjc.6606032}}</ref> A 2014 meta-analysis found no relationship between fruits and vegetables and cancer.<ref>{{cite journal |vauthors=Wang X, Ouyang Y, Liu J, Zhu M, Zhao G, Bao W, Hu FB |title=Fruit and vegetable consumption and mortality from all causes, cardiovascular disease, and cancer: systematic review and dose-response meta-analysis of prospective cohort studies |journal=BMJ |volume=349 |pages=g4490 |date=July 2014 |pmid=25073782 |pmc=4115152 |doi=10.1136/bmj.g4490}}</ref> Coffee is associated with a reduced risk of [[liver cancer]].<ref name="pmid17484871">{{cite journal |vauthors=Larsson SC, Wolk A |title=Coffee consumption and risk of liver cancer: a meta-analysis |journal=Gastroenterology |volume=132 |issue=5 |pages=1740–5 |date=May 2007 |pmid=17484871 |doi=10.1053/j.gastro.2007.03.044|url=http://www.gastrojournal.org/article/S0016508507005689/pdf |doi-access=free }}</ref> Studies have linked excessive consumption of [[red meat|red]] or [[processed meat]] to an increased risk of breast cancer, [[Colorectal cancer|colon cancer]] and [[pancreatic cancer]], a phenomenon that could be due to the presence of [[carcinogens]] in meats cooked at high temperatures.<ref name="pmid19838915">{{cite journal |vauthors=Zheng W, Lee SA |title=Well-done meat intake, heterocyclic amine exposure, and cancer risk |journal=Nutrition and Cancer |volume=61 |issue=4 |pages=437–46 |year=2009 |pmid=19838915 |pmc=2769029 |doi=10.1080/01635580802710741}}</ref><ref name="pmid20374790">{{cite journal |vauthors=Ferguson LR |title=Meat and cancer |journal=Meat Science |volume=84 |issue=2 |pages=308–13 |date=February 2010 |pmid=20374790 |doi=10.1016/j.meatsci.2009.06.032}}</ref> In 2015 the [[International Agency for Research on Cancer|IARC]] reported that eating [[processed meat]] (e.g., [[bacon]], [[ham]], [[hot dogs]], [[sausages]]) and, to a lesser degree, [[red meat]] was linked to some cancers.<ref name="WHO-20151026">{{cite news |author=Staff |title=World Health Organization – IARC Monographs evaluate consumption of red meat and processed meat |url=http://www.iarc.fr/en/media-centre/pr/2015/pdfs/pr240_E.pdf |date=26 October 2015 |work=[[International Agency for Research on Cancer]] |access-date=26 October 2015 |url-status=live |archive-url=https://web.archive.org/web/20151026144543/http://www.iarc.fr/en/media-centre/pr/2015/pdfs/pr240_E.pdf |archive-date=26 October 2015}}</ref><ref name="NYT-20151026">{{cite news | vauthors = Hauser C |title=W.H.O. Report Links Some Cancers With Processed or Red Meat |url=https://www.nytimes.com/2015/10/27/health/report-links-some-types-of-cancer-with-processed-or-red-meat.html |date=26 October 2015 |work=[[The New York Times]] |access-date=26 October 2015 |url-status=live |archive-url=https://web.archive.org/web/20151026173834/http://www.nytimes.com/2015/10/27/health/report-links-some-types-of-cancer-with-processed-or-red-meat.html |archive-date=26 October 2015}}</ref> [[Healthy diet|Dietary recommendations]] for cancer prevention typically include an emphasis on vegetables, fruit, [[whole grains]] and fish and an avoidance of processed and red meat (beef, pork, lamb), [[animal fats]], [[pickled foods]] and [[Carbohydrate#Nutrition|refined carbohydrates]].<ref name=Kushi2012/><ref name=Diet11/> === Medication === Medications can be used to prevent cancer in a few circumstances.<ref>Holland Chp.33</ref> In the general population, [[Non-steroidal anti-inflammatory drug|NSAIDs]] reduce the risk of [[colorectal cancer]]; however, due to cardiovascular and gastrointestinal side effects, they cause overall harm when used for prevention.<ref name="pmid17339623">{{cite journal |vauthors=Rostom A, Dubé C, Lewin G, Tsertsvadze A, Barrowman N, Code C, Sampson M, Moher D |title=Nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors for primary prevention of colorectal cancer: a systematic review prepared for the U.S. Preventive Services Task Force |journal=Annals of Internal Medicine |volume=146 |issue=5 |pages=376–89 |date=March 2007 |pmid=17339623 |doi=10.7326/0003-4819-146-5-200703060-00010|doi-access=free }}</ref> [[Aspirin]] has been found to reduce the risk of death from cancer by about 7%.<ref name="pmid21144578">{{cite journal |vauthors=Rothwell PM, Fowkes FG, Belch JF, Ogawa H, Warlow CP, Meade TW |s2cid=22950940 |title=Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials |journal=Lancet |volume=377 |issue=9759 |pages=31–41 |date=January 2011 |pmid=21144578 |doi=10.1016/S0140-6736(10)62110-1}}</ref> [[COX-2 inhibitor]]s may decrease the rate of [[polyp (medicine)|polyp]] formation in people with [[familial adenomatous polyposis]]; however, it is associated with the same adverse effects as NSAIDs.<ref name="pmid20594533">{{cite journal |vauthors=Cooper K, Squires H, Carroll C, Papaioannou D, Booth A, Logan RF, Maguire C, Hind D, Tappenden P |title=Chemoprevention of colorectal cancer: systematic review and economic evaluation |journal=Health Technology Assessment |volume=14 |issue=32 |pages=1–206 |date=June 2010 |pmid=20594533 |doi=10.3310/hta14320|doi-access=free }}</ref> Daily use of [[tamoxifen]] or [[raloxifene]] reduce the risk of breast cancer in high-risk women.<ref name="pmid19020189">{{cite journal |vauthors=Thomsen A, Kolesar JM |title=Chemoprevention of breast cancer |journal=American Journal of Health-System Pharmacy |volume=65 |issue=23 |pages=2221–28 |date=December 2008 |pmid=19020189 |doi=10.2146/ajhp070663}}</ref> The benefit versus harm for [[5-alpha-reductase inhibitor]] such as [[finasteride]] is not clear.<ref name="pmid18425978">{{cite journal |vauthors=Wilt TJ, MacDonald R, Hagerty K, Schellhammer P, Kramer BS |title=Five-alpha-reductase Inhibitors for prostate cancer prevention |veditors=Wilt TJ |journal=The Cochrane Database of Systematic Reviews |issue=2 |pages=CD007091 |date=April 2008 |pmid=18425978 |doi=10.1002/14651858.CD007091|pmc=11270836 }}</ref> [[Vitamin]] supplementation does not appear to be effective at preventing cancer.<ref name="pmid20939459">{{cite journal |title=Vitamins and minerals: not for cancer or cardiovascular prevention |journal=Prescrire International |volume=19 |issue=108 |page=182 |date=August 2010 |pmid=20939459 |url=http://english.prescrire.org/en/81/168/46461/0/2010/ArchiveNewsDetails.aspx?page=2 |url-status=live |archive-url=https://web.archive.org/web/20120525134048/http://english.prescrire.org/en/81/168/46461/0/2010/ArchiveNewsDetails.aspx?page=2 |archive-date=25 May 2012}}</ref> While low blood levels of [[vitamin D]] are correlated with increased cancer risk,<ref name="pmid16595781">{{cite journal |vauthors=Giovannucci E, Liu Y, Rimm EB, Hollis BW, Fuchs CS, Stampfer MJ, Willett WC |title=Prospective study of predictors of vitamin D status and cancer incidence and mortality in men |journal=Journal of the National Cancer Institute |volume=98 |issue=7 |pages=451–59 |date=April 2006 |pmid=16595781 |doi=10.1093/jnci/djj101 |citeseerx=10.1.1.594.1654}}</ref><ref>{{cite web |title=Vitamin D Has Role in Colon Cancer Prevention |url=http://www.cancer.org/docroot/NWS/content/NWS_1_1x_Vitamin_D_Has_Role_in_Colon_Cancer_Prevention.asp |access-date=27 July 2007 |archive-url=https://web.archive.org/web/20061204052746/http://www.cancer.org/docroot/NWS/content/NWS_1_1x_Vitamin_D_Has_Role_in_Colon_Cancer_Prevention.asp |archive-date=4 December 2006 }}</ref><ref>{{cite journal |vauthors=Holick MF |title=Vitamin D, sunlight and cancer connection |journal=Anti-Cancer Agents in Medicinal Chemistry |volume=13 |issue=1 |pages=70–82 |date=January 2013 |pmid=23094923 |doi=10.2174/187152013804487308}}</ref> whether this relationship is causal and vitamin D supplementation is protective is not determined.<ref name="pmid16595770">{{cite journal |vauthors=Schwartz GG, Blot WJ |title=Vitamin D status and cancer incidence and mortality: something new under the sun |journal=Journal of the National Cancer Institute |volume=98 |issue=7 |pages=428–30 |date=April 2006 |pmid=16595770 |doi=10.1093/jnci/djj127|doi-access=free }}</ref><ref name=Futil2014>{{cite journal |vauthors=Bolland MJ, Grey A, Gamble GD, Reid IR |title=The effect of vitamin D supplementation on skeletal, vascular, or cancer outcomes: a trial sequential meta-analysis |journal=The Lancet. Diabetes & Endocrinology |volume=2 |issue=4 |pages=307–320 |date=April 2014 |pmid=24703049 |doi=10.1016/S2213-8587(13)70212-2}}</ref> One 2014 review found that supplements had no significant effect on cancer risk.<ref name=Futil2014/> Another 2014 review concluded that vitamin D<sub>3</sub> may decrease the risk of death from cancer (one fewer death in 150 people treated over 5 years), but concerns with the quality of the data were noted.<ref>{{cite journal |vauthors=Bjelakovic G, Gluud LL, Nikolova D, Whitfield K, Wetterslev J, Simonetti RG, Bjelakovic M, Gluud C |s2cid=205189615 |title=Vitamin D supplementation for prevention of mortality in adults |journal=The Cochrane Database of Systematic Reviews |volume=1 |issue=1 |pages=CD007470 |date=January 2014 |pmid=24414552 |doi=10.1002/14651858.cd007470.pub3|pmc=11285307 }}</ref> [[Beta-Carotene]] supplementation increases lung cancer rates in those who are high risk.<ref name="pmid21738614">{{cite journal | vauthors = Fritz H, Kennedy D, Fergusson D, Fernandes R, Doucette S, Cooley K, Seely A, Sagar S, Wong R, Seely D | title = Vitamin A and retinoid derivatives for lung cancer: a systematic review and meta analysis | journal = PLOS ONE | volume = 6 | issue = 6 | pages = e21107 | year = 2011 | pmid = 21738614 | pmc = 3124481 | doi = 10.1371/journal.pone.0021107 | bibcode = 2011PLoSO...621107F | veditors = Minna JD | doi-access = free }}</ref> [[Folic acid]] supplementation is not effective in preventing colon cancer and may increase colon polyps.<ref name="pmid17551129">{{cite journal | vauthors = Cole BF, Baron JA, Sandler RS, Haile RW, Ahnen DJ, Bresalier RS, McKeown-Eyssen G, Summers RW, Rothstein RI, Burke CA, Snover DC, Church TR, Allen JI, Robertson DJ, Beck GJ, Bond JH, Byers T, Mandel JS, Mott LA, Pearson LH, Barry EL, Rees JR, Marcon N, Saibil F, Ueland PM, Greenberg ER | title = Folic acid for the prevention of colorectal adenomas: a randomized clinical trial | journal = JAMA | volume = 297 | issue = 21 | pages = 2351–2359 | date = June 2007 | pmid = 17551129 | doi = 10.1001/jama.297.21.2351 | doi-access = free }}</ref> Selenium supplementation has not been shown to reduce the risk of cancer.<ref>{{cite journal | vauthors = Vinceti M, Filippini T, Del Giovane C, Dennert G, Zwahlen M, Brinkman M, Zeegers MP, Horneber M, D'Amico R, Crespi CM | title = Selenium for preventing cancer | journal = The Cochrane Database of Systematic Reviews | volume = 1 | issue = 1 | pages = CD005195 | date = January 2018 | pmid = 29376219 | pmc = 6491296 | doi = 10.1002/14651858.CD005195.pub4 }}</ref> === Vaccination === [[Vaccine]]s have been developed that prevent infection by some [[carcinogen]]ic viruses.<ref name=vacc_facts_nci>{{cite web |url=https://www.cancer.gov/about-cancer/causes-prevention/vaccines-fact-sheet |title=Cancer Vaccine Fact Sheet |publisher=[[National Cancer Institute|NCI]] |date=8 June 2006 |access-date=28 March 2018 }}</ref> [[HPV vaccine|Human papillomavirus vaccine]] ([[Gardasil]] and [[Cervarix]]) decrease the risk of developing [[cervical cancer]].<ref name=vacc_facts_nci/> The [[hepatitis B vaccine]] prevents infection with hepatitis B virus and thus decreases the risk of liver cancer.<ref name=vacc_facts_nci/> The administration of human papillomavirus and hepatitis B vaccinations is recommended where resources allow.<ref name="pmid24176569">{{cite journal |author4-link=Ding-Shinn Chen |vauthors=Lertkhachonsuk AA, Yip CH, Khuhaprema T, Chen DS, Plummer M, Jee SH, Toi M, Wilailak S |title=Cancer prevention in Asia: resource-stratified guidelines from the Asian Oncology Summit 2013 |journal=The Lancet. Oncology |volume=14 |issue=12 |pages=e497–507 |date=November 2013 |pmid=24176569 |doi=10.1016/S1470-2045(13)70350-4|arxiv=cond-mat/0606434 }}</ref> == Screening == {{Main|Cancer screening}} Unlike diagnostic efforts prompted by [[symptom]]s and [[medical sign]]s, cancer screening involves efforts to detect cancer after it has formed, but before any noticeable symptoms appear.<ref name=NIH>{{cite web |url=https://www.cancer.gov/about-cancer/screening/patient-screening-overview-pdq |title=Cancer Screening Overview (PDQ®)–Patient Version |publisher=National Cancer Institute |access-date=28 March 2018 |date=13 January 2010}}</ref> This may involve [[physical examination]], [[blood test|blood]] or [[urinalysis|urine tests]] or [[medical imaging]].<ref name=NIH/> [[Cancer biomarker|Cancer screening]] is not available for many types of cancers. Even when tests are available, they may not be recommended for everyone. ''[[Universal screening]]'' or ''mass screening'' involves screening everyone.<ref name=Wilson>Wilson JMG, Jungner G. (1968) [https://web.archive.org/web/20110604205519/http://whqlibdoc.who.int/php/WHO_PHP_34.pdf Principles and practice of screening for disease.] Geneva: [[World Health Organization]]. Public Health Papers, No. 34.</ref> ''Selective screening'' identifies people who are at higher risk, such as people with a family history.<ref name=Wilson/> Several factors are considered to determine whether the benefits of screening outweigh the risks and the costs of screening.<ref name=NIH/> These factors include: * Possible harms from the screening test: for example, X-ray images involve exposure to potentially harmful [[ionizing radiation]] * The likelihood of the test correctly identifying cancer * The likelihood that cancer is present: Screening is not normally useful for rare cancers. * Possible harms from follow-up procedures * Whether a suitable treatment is available * Whether early detection improves treatment outcomes * Whether cancer will ever need treatment * Whether the test is acceptable to the people: If a screening test is too burdensome (for example, extremely painful), then people will refuse to participate.<ref name=Wilson/> * Cost === Recommendations === ==== U.S. Preventive Services Task Force ==== The [[U.S. Preventive Services Task Force]] (USPSTF) issues recommendations for various cancers: * Strongly recommends [[cervical cancer]] screening in women who are [[sexually active]] and have a [[cervix]] at least until the age of 65.<ref>{{cite web |url=http://www.uspreventiveservicestaskforce.org/uspstf/uspscerv.htm |title=Screening for Cervical Cancer |year=2003 |website=[[U.S. Preventive Services Task Force]] |archive-url=https://web.archive.org/web/20101223103447/http://www.uspreventiveservicestaskforce.org/uspstf/uspscerv.htm |archive-date=23 December 2010|access-date=21 December 2010 }}</ref> * Recommend that Americans be screened for [[colorectal cancer]] via [[fecal occult blood]] testing, [[sigmoidoscopy]], or [[colonoscopy]] starting at age 50 until age 75.<ref>{{cite web |url=http://www.uspreventiveservicestaskforce.org/uspstf/uspscolo.htm |title=Screening for Colorectal Cancer |year=2008 |website=[[U.S. Preventive Services Task Force]] |archive-url=https://web.archive.org/web/20150207110937/http://www.uspreventiveservicestaskforce.org/uspstf/uspscolo.htm |archive-date=7 February 2015|access-date=21 December 2010 }}</ref> * Evidence is insufficient to recommend for or against screening for [[skin cancer]],<ref>{{cite web |url=http://www.uspreventiveservicestaskforce.org/uspstf/uspsskca.htm |title=Screening for Skin Cancer |year=2009 |website=[[U.S. Preventive Services Task Force]] |archive-url=https://web.archive.org/web/20110108054103/http://www.uspreventiveservicestaskforce.org/uspstf/uspsskca.htm |archive-date=8 January 2011|access-date=21 December 2010 }}</ref> [[oral cancer]],<ref>{{cite web |url=http://www.uspreventiveservicestaskforce.org/uspstf/uspsoral.htm |title=Screening for Oral Cancer |year=2004 |website=[[U.S. Preventive Services Task Force]] |archive-url=https://web.archive.org/web/20101024144627/http://www.uspreventiveservicestaskforce.org/uspstf/uspsoral.htm |archive-date=24 October 2010|access-date=21 December 2010 }}</ref> lung cancer,<ref>{{cite web |url=http://www.uspreventiveservicestaskforce.org/uspstf/uspslung.htm |title=Lung Cancer Screening |year=2004 |website=[[U.S. Preventive Services Task Force]] |archive-url=https://web.archive.org/web/20101104055403/http://www.uspreventiveservicestaskforce.org/uspstf/uspslung.htm |archive-date=4 November 2010|access-date=21 December 2010 }}</ref> or [[prostate cancer]] in men under 75.<ref name="USPSTFPr08">{{cite web |url=http://www.uspreventiveservicestaskforce.org/uspstf/uspsprca.htm |title=Screening for Prostate Cancer |year=2008 |website=[[U.S. Preventive Services Task Force]] |archive-url=https://web.archive.org/web/20101231105229/http://www.uspreventiveservicestaskforce.org/uspstf/uspsprca.htm |archive-date=31 December 2010|access-date=21 December 2010 }}</ref> * Routine screening is not recommended for [[bladder cancer]],<ref>{{cite web |url=http://www.uspreventiveservicestaskforce.org/uspstf/uspsblad.htm |title=Screening for Bladder Cancer |year=2004 |website=[[U.S. Preventive Services Task Force]] |archive-url=https://web.archive.org/web/20100823053849/http://www.uspreventiveservicestaskforce.org/uspstf/uspsblad.htm |archive-date=23 August 2010|access-date=21 December 2010 }}</ref> [[testicular cancer]],<ref>{{cite web |url=http://www.uspreventiveservicestaskforce.org/uspstf/uspstest.htm |title=Screening for Testicular Cancer |year=2004 |website=[[U.S. Preventive Services Task Force]] |archive-url=http://arquivo.pt/wayback/20160515181437/http://www.uspreventiveservicestaskforce.org/uspstf/uspstest.htm |archive-date=15 May 2016|access-date=21 December 2010 }}</ref> [[ovarian cancer]],<ref>{{cite web |url=http://www.uspreventiveservicestaskforce.org/uspstf/uspsovar.htm |title=Screening for Ovarian Cancer |year=2004 |website=[[U.S. Preventive Services Task Force]] |archive-url=https://web.archive.org/web/20101023221553/http://www.uspreventiveservicestaskforce.org/uspstf/uspsovar.htm |archive-date=23 October 2010|access-date=21 December 2010 }}</ref> [[pancreatic cancer]],<ref>{{cite web |url=http://www.uspreventiveservicestaskforce.org/uspstf/uspspanc.htm |title=Screening for Pancreatic Cancer |year=2004 |website=[[U.S. Preventive Services Task Force]] |archive-url=https://web.archive.org/web/20101121030321/http://www.uspreventiveservicestaskforce.org/uspstf/uspspanc.htm |archive-date=21 November 2010|access-date=21 December 2010 }}</ref> or [[prostate cancer]].<ref name="USPSTF-20111007">{{cite journal | vauthors = Chou R, Croswell JM, Dana T, Bougatsos C, Blazina I, Fu R, Gleitsmann K, Koenig HC, Lam C, Maltz A, Rugge JB, Lin K | title = Screening for prostate cancer: a review of the evidence for the U.S. Preventive Services Task Force | journal = Annals of Internal Medicine | volume = 155 | issue = 11 | pages = 762–71 | date = December 2011 | pmid = 21984740 | doi = 10.7326/0003-4819-155-11-201112060-00375 | publisher = [[United States Preventive Services Task Force]]| doi-access = free}}</ref> * Recommends [[mammography]] for breast cancer screening every two years from ages 50–74, but does not recommend either [[breast self-examination]] or [[Breast cancer screening|clinical breast examination]].<ref name="USPSTFBr09">{{cite web |url=http://www.uspreventiveservicestaskforce.org/uspstf/uspsbrca.htm |title=Screening for Breast Cancer |year=2009 |website=[[U.S. Preventive Services Task Force]] |archive-url=https://web.archive.org/web/20130102015424/http://www.uspreventiveservicestaskforce.org/uspstf/uspsbrca.htm |archive-date=2 January 2013|access-date=21 December 2010 }}</ref> A 2013 [[Cochrane review]] concluded that breast cancer screening by mammography had no effect in reducing mortality because of overdiagnosis and overtreatment.<ref>{{cite journal | vauthors = Gøtzsche PC, Jørgensen KJ | title = Screening for breast cancer with mammography | journal = The Cochrane Database of Systematic Reviews | issue = 6 | pages = CD001877 | date = June 2013 | volume = 2013 | pmid = 23737396 | doi = 10.1002/14651858.CD001877.pub5 | pmc = 6464778 }}</ref> ==== Japan ==== Screens for [[gastric cancer]] using [[photofluorography]] due to the high incidence there.<ref name=Epi11/> === Genetic testing === {{See also|Cancer syndrome}} {| class="wikitable floatright" style="text-align:center" width="50%" |- ! Gene ! Cancer types |- | [[BRCA1]], [[BRCA2]] | Breast, ovarian, pancreatic |- | [[Hereditary nonpolyposis colorectal cancer|HNPCC]], [[MLH1]], [[MSH2]], [[MSH6]], [[PMS1]], [[PMS2]] | Colon, uterine, small bowel, stomach, urinary tract |} [[Genetic testing]] for individuals at high risk of certain cancers is recommended by unofficial groups.<ref name=pmid24176569/><ref name=BRCA08>{{cite journal |vauthors=Gulati AP, [[Susan Domchek|Domchek SM]] |s2cid=29630942 |title=The clinical management of BRCA1 and BRCA2 mutation carriers |journal=Current Oncology Reports |volume=10 |issue=1 |pages=47–53 |date=January 2008 |pmid=18366960 |doi=10.1007/s11912-008-0008-9}}</ref> Carriers of these mutations may then undergo enhanced surveillance, chemoprevention, or preventative surgery to reduce their subsequent risk.<ref name=BRCA08/> == Management == {{Main|Treatment of cancer|Oncology|}} Many treatment options for cancer exist. The primary ones include surgery, [[chemotherapy]], [[radiation therapy]], [[hormonal therapy (oncology)|hormonal therapy]], [[targeted therapy]] and [[palliative care]]. Which treatments are used depends on the type, location and grade of the cancer as well as the patient's health and preferences. The [[therapy#By treatment intent|treatment intent]] may or may not be curative.{{citation needed|date=March 2024}} === Chemotherapy === [[Chemotherapy]] is the treatment of cancer with one or more [[Cytotoxicity|cytotoxic]] anti-[[neoplastic]] drugs ([[list of chemotherapeutic agents|chemotherapeutic agents]]) as part of a [[chemotherapy regimen|standardized regimen]]. The term encompasses a variety of drugs, which are divided into broad categories such as [[Alkylating antineoplastic agent|alkylating agents]] and [[antimetabolite]]s.<ref name="Lind2008">{{cite journal | vauthors = Lind MJ |title=Principles of cytotoxic chemotherapy |journal=Medicine |year=2008 |volume=36 |issue=1 |pages=19–23 |doi=10.1016/j.mpmed.2007.10.003 }}</ref> Traditional chemotherapeutic agents act by killing cells that divide rapidly, a critical property of most cancer cells. It was found that providing combined cytotoxic drugs is better than a single drug, a process called the [[combination therapy]], which has an advantage in the statistics of survival and response to the tumor and in the progress of the disease.<ref>{{cite book | vauthors = Frei III E, Eder JP |title=Combination Chemotherapy |date=2003 |url=https://www.ncbi.nlm.nih.gov/books/NBK13955/ |access-date=4 April 2020 |language=en}}</ref> A Cochrane review concluded that combined therapy was more effective in treating metastasized breast cancer. However, generally it is not certain whether combination chemotherapy leads to better health outcomes, when both survival and toxicity are considered.<ref>{{cite journal | vauthors = Dear RF, McGeechan K, Jenkins MC, Barratt A, Tattersall MH, Wilcken N | title = Combination versus sequential single agent chemotherapy for metastatic breast cancer | journal = The Cochrane Database of Systematic Reviews | issue = 12 | pages = CD008792 | date = December 2013 | volume = 2021 | pmid = 24347031 | doi = 10.1002/14651858.CD008792.pub2 | pmc = 8094913 }}</ref> [[Targeted therapy]] is a form of chemotherapy that targets specific molecular differences between cancer and normal cells. The first targeted therapies blocked the [[estrogen receptor]] molecule, inhibiting the growth of breast cancer. Another common example is the class of [[Bcr-Abl tyrosine-kinase inhibitor|Bcr-Abl inhibitors]], which are used to treat [[chronic myelogenous leukemia]] (CML).<ref name=TCT2018/> Currently, targeted therapies exist for many of the most common cancer types, including [[bladder cancer]], breast cancer, [[colorectal cancer]], [[kidney cancer]], [[leukemia]], [[liver cancer]], lung cancer, [[lymphoma]], [[pancreatic cancer]], [[prostate cancer]], [[skin cancer]], and [[thyroid cancer]] as well as other cancer types.<ref name=TCT2018/> The efficacy of chemotherapy depends on the type of cancer and the stage. In combination with surgery, chemotherapy has proven useful in cancer types including breast cancer, colorectal cancer, [[pancreatic cancer]], [[osteosarcoma|osteogenic sarcoma]], [[testicular cancer]], ovarian cancer and certain lung cancers.<ref name=HollandTx40/> Chemotherapy is curative for some cancers, such as some [[leukemias]],<ref>{{cite journal |vauthors=Nastoupil LJ, Rose AC, Flowers CR |title=Diffuse large B-cell lymphoma: current treatment approaches |journal=Oncology |volume=26 |issue=5 |pages=488–95 |date=May 2012 |pmid=22730604}}</ref><ref>{{cite journal |vauthors=Freedman A |title=Follicular lymphoma: 2012 update on diagnosis and management |journal=American Journal of Hematology |volume=87 |issue=10 |pages=988–95 |date=October 2012 |pmid=23001911 |doi=10.1002/ajh.23313|s2cid=35447562 |doi-access=free }}</ref> ineffective in some [[brain tumors]],<ref>{{cite journal |vauthors=Rampling R, James A, Papanastassiou V |title=The present and future management of malignant brain tumours: surgery, radiotherapy, chemotherapy |journal=Journal of Neurology, Neurosurgery, and Psychiatry |volume=75 |issue=Suppl 2 |pages=ii24–30 |date=June 2004 |pmid=15146036 |pmc=1765659 |doi=10.1136/jnnp.2004.040535}}</ref> and needless in others, such as most [[non-melanoma skin cancer]]s.<ref>{{cite journal |vauthors=Madan V, Lear JT, Szeimies RM |title=Non-melanoma skin cancer |journal=Lancet |volume=375 |issue=9715 |pages=673–85 |date=February 2010 |pmid=20171403 |doi=10.1016/S0140-6736(09)61196-X|pmc=3339125 }}</ref> The effectiveness of chemotherapy is often limited by its toxicity to other tissues in the body. Even when chemotherapy does not provide a permanent cure, it may be useful to reduce symptoms such as pain or to reduce the size of an inoperable tumor in the hope that surgery will become possible in the future.{{Citation needed|date=January 2025}} === Radiation === [[Radiation therapy]] involves the use of [[ionizing radiation]] in an attempt to either cure or improve symptoms.<!--<ref name=H41/> --> It works by damaging the DNA of cancerous tissue, causing [[mitotic catastrophe]] resulting in the death of the cancer cells.<ref>{{cite journal | vauthors = Vitale I, Galluzzi L, Castedo M, Kroemer G | title = Mitotic catastrophe: a mechanism for avoiding genomic instability | journal = Nature Reviews. Molecular Cell Biology | volume = 12 | issue = 6 | pages = 385–392 | date = June 2011 | pmid = 21527953 | doi = 10.1038/nrm3115 | s2cid = 22483746 }}</ref> To spare normal tissues (such as skin or organs, which radiation must pass through to treat the tumor), shaped radiation beams are aimed from multiple exposure angles to intersect at the tumor, providing a much larger dose there than in the surrounding, healthy tissue. As with chemotherapy, cancers vary in their response to radiation therapy.<ref>{{cite book | vauthors = Bomford CK, Kunkler IH, Walter J | title = Walter and Miller's Textbook of Radiation therapy | edition = 6th | page = 311 }}</ref><ref>{{cite web |url=http://www.gpnotebook.co.uk/simplepage.cfm?ID=2060451853 |title=tumour radiosensitivity – General Practice Notebook | vauthors = McMorran J, Crowther D, McMorran S, Youngmin S, Wacogne I, Pleat J, Clive P |url-status=live |archive-url=https://web.archive.org/web/20150924023421/http://www.gpnotebook.co.uk/simplepage.cfm?ID=2060451853 |archive-date=24 September 2015}}</ref><ref>{{cite web |url=https://patient.info/doctor/radiotherapy-pro |title=Radiotherapy |publisher=[[Patient UK]] | vauthors = Tidy C |date=23 December 2015 | url-status = live |archive-url=https://web.archive.org/web/20170709084620/https://patient.info/doctor/radiotherapy-pro |archive-date=9 July 2017}} Last Checked: 23 December 2015</ref> Radiation therapy is used in about half of cases. The radiation can be either from internal sources ([[brachytherapy]]) or external sources. The radiation is most commonly low energy X-rays for treating skin cancers, while higher energy X-rays are used for cancers within the body.<ref>{{cite journal |vauthors=Hill R, Healy B, Holloway L, Kuncic Z, Thwaites D, Baldock C |s2cid=18082594 |title=Advances in kilovoltage x-ray beam dosimetry |journal=Physics in Medicine and Biology |volume=59 |issue=6 |pages=R183–231 |date=March 2014 |pmid=24584183 |doi=10.1088/0031-9155/59/6/r183|bibcode=2014PMB....59R.183H }}</ref> Radiation is typically used in addition to surgery and/or chemotherapy. For certain types of cancer, such as early [[head and neck cancer]], it may be used alone.<ref name=H41/> Radiation therapy after surgery for brain metastases has been shown to not improve overall survival in patients compared to surgery alone.<ref>{{Cite web |date=13 August 2019 |title=Radiation Therapy for Brain Metastases: A Systematic Review |url=https://www.pcori.org/research-results/2019/radiation-therapy-brain-metastases-systematic-review |access-date=10 October 2023 |website=PCORI |language=en}}</ref> For painful [[bone metastasis]], radiation therapy has been found to be effective in about 70% of patients.<ref name="H41">Holland Chp. 41</ref> === Surgery === Surgery is the primary method of treatment for most isolated, solid cancers and may play a role in palliation and prolongation of survival. It is typically an important part of the definitive diagnosis and staging of tumors, as biopsies are usually required. In localized cancer, surgery typically attempts to remove the entire mass along with, in certain cases, the [[lymph node]]s in the area. For some types of cancer this is sufficient to eliminate the cancer.<ref name=HollandTx40>Holland Chp. 40</ref> === Palliative care === [[Palliative care]] is treatment that attempts to help the patient feel better and may be combined with an attempt to treat the cancer. Palliative care includes action to reduce physical, emotional, spiritual and psycho-social distress. Unlike treatment that is aimed at directly killing cancer cells, the primary goal of palliative care is to improve [[quality of life (healthcare)|quality of life]]. People at all stages of cancer treatment typically receive some kind of palliative care. In some cases, [[Specialty (medicine)|medical specialty]] [[professional organizations]] recommend that patients and physicians respond to cancer only with palliative care. This applies to patients who:<ref name="ASCOfive">{{Cite journal |author1=American Society of Clinical Oncology |author1-link=American Society of Clinical Oncology |title=Five Things Physicians and Patients Should Question |journal=Choosing Wisely: An Initiative of the ABIM Foundation |url=http://choosingwisely.org/wp-content/uploads/2012/04/5things_12_factsheet_Amer_Soc_Clin_Onc.pdf |access-date=14 August 2012 |archive-url=https://web.archive.org/web/20120731073425/http://choosingwisely.org/wp-content/uploads/2012/04/5things_12_factsheet_Amer_Soc_Clin_Onc.pdf |archive-date=31 July 2012}}<br/>* The American Society of Clinical Oncology made this recommendation based on various cancers.</ref> * for lung cancer, see {{cite journal |vauthors=Azzoli CG, Temin S, Aliff T, Baker S, Brahmer J, Johnson DH, Laskin JL, Masters G, Milton D, Nordquist L, Pao W, Pfister DG, Piantadosi S, Schiller JH, Smith R, Smith TJ, Strawn JR, Trent D, Giaccone G |title=2011 Focused Update of 2009 American Society of Clinical Oncology Clinical Practice Guideline Update on Chemotherapy for Stage IV Non-Small-Cell Lung Cancer |journal=Journal of Clinical Oncology |volume=29 |issue=28 |pages=3825–31 |date=October 2011 |pmid=21900105 |pmc=3675703 |doi=10.1200/JCO.2010.34.2774 | author20 = American Society of Clinical Oncology}} and {{cite journal |vauthors=Ettinger DS, Akerley W, Bepler G, Blum MG, Chang A, Cheney RT, Chirieac LR, D'Amico TA, Demmy TL, Ganti AK, Govindan R, Grannis FW, Jahan T, Jahanzeb M, Johnson DH, Kessinger A, Komaki R, Kong FM, Kris MG, Krug LM, Le QT, Lennes IT, Martins R, O'Malley J, Osarogiagbon RU, Otterson GA, Patel JD, Pisters KM, Reckamp K, Riely GJ, Rohren E, Simon GR, Swanson SJ, Wood DE, Yang SC |title=Non-small cell lung cancer |journal=Journal of the National Comprehensive Cancer Network |volume=8 |issue=7 |pages=740–801 |date=July 2010 |pmid=20679538| doi = 10.6004/jnccn.2010.0056 |doi-access=free }} * for breast cancer, see {{cite journal |vauthors=Carlson RW, Allred DC, Anderson BO, Burstein HJ, Carter WB, Edge SB, Erban JK, Farrar WB, Goldstein LJ, Gradishar WJ, Hayes DF, Hudis CA, Jahanzeb M, Kiel K, Ljung BM, Marcom PK, Mayer IA, McCormick B, Nabell LM, Pierce LJ, Reed EC, Smith ML, Somlo G, Theriault RL, Topham NS, Ward JH, Winer EP, Wolff AC |title=Breast cancer. Clinical practice guidelines in oncology |journal=Journal of the National Comprehensive Cancer Network |volume=7 |issue=2 |pages=122–92 |date=February 2009 |pmid=19200416 |author29=NCCN Breast Cancer Clinical Practice Guidelines Panel| doi = 10.6004/jnccn.2009.0012 |doi-access=free }} * for colon cancer, see {{cite journal |vauthors=Engstrom PF, Arnoletti JP, Benson AB, Chen YJ, Choti MA, Cooper HS, Covey A, Dilawari RA, Early DS, Enzinger PC, Fakih MG, Fleshman J, Fuchs C, Grem JL, Kiel K, Knol JA, Leong LA, Lin E, Mulcahy MF, Rao S, Ryan DP, Saltz L, Shibata D, Skibber JM, Sofocleous C, Thomas J, Venook AP, Willett C |title=NCCN Clinical Practice Guidelines in Oncology: colon cancer |journal=Journal of the National Comprehensive Cancer Network |volume=7 |issue=8 |pages=778–831 |date=September 2009 |pmid=19755046 |author29=National Comprehensive Cancer Network|doi=10.6004/jnccn.2009.0056 |doi-access=free }} * for other general statements see {{cite journal |vauthors=Smith TJ, Hillner BE |title=Bending the cost curve in cancer care |journal=The New England Journal of Medicine |volume=364 |issue=21 |pages=2060–5 |date=May 2011 |pmid=21612477 |doi=10.1056/NEJMsb1013826|pmc=4042405 }} and {{cite journal |vauthors=Peppercorn JM, Smith TJ, Helft PR, Debono DJ, Berry SR, Wollins DS, Hayes DM, Von Roenn JH, Schnipper LE |title=American society of clinical oncology statement: toward individualized care for patients with advanced cancer |journal=Journal of Clinical Oncology |volume=29 |issue=6 |pages=755–60 |date=February 2011 |pmid=21263086 |doi=10.1200/JCO.2010.33.1744 | author10 = American Society of Clinical Oncology|s2cid=40873748 }} * Display low [[performance status]], implying limited ability to care for themselves * Received no benefit from prior [[Evidence-based medicine|evidence-based treatments]] * Are not eligible to participate in any appropriate [[clinical trial]] * No strong evidence implies that treatment would be effective Palliative care may be confused with [[hospice]] and therefore only indicated when people approach [[End-of-life care|end of life]]. Like hospice care, palliative care attempts to help the patient cope with their immediate needs and to increase comfort. Unlike hospice care, palliative care does not require people to stop treatment aimed at the cancer.{{Citation needed|date=January 2025}} Multiple national [[medical guideline]]s recommend early palliative care for patients whose cancer has produced distressing symptoms or who need help coping with their illness. In patients first diagnosed with metastatic disease, palliative care may be immediately indicated. Palliative care is indicated for patients with a prognosis of less than 12 months of life even given aggressive treatment.<ref>{{cite web |url=http://www.nccn.org/professionals/physician_gls/default.asp |title=NCCN Guidelines |url-status=live |archive-url=https://web.archive.org/web/20080514153600/http://www.nccn.org/professionals/physician_gls/default.asp |archive-date=14 May 2008}}</ref><ref>{{cite web |url=http://www.nationalconsensusproject.org/guideline.pdf |title=Clinical Practice Guidelines for Quality Palliative Care |publisher=The National Consensus Project for Quality Palliative Care (NCP) |archive-url=https://web.archive.org/web/20110516082645/http://www.nationalconsensusproject.org/Guideline.pdf |archive-date=16 May 2011}}</ref><ref>{{cite journal |vauthors=Levy MH, Back A, Bazargan S, Benedetti C, Billings JA, Block S, Bruera E, Carducci MA, Dy S, Eberle C, Foley KM, Harris JD, Knight SJ, Milch R, Rhiner M, Slatkin NE, Spiegel D, Sutton L, Urba S, Von Roenn JH, Weinstein SM |s2cid=44343423 |title=Palliative care. Clinical practice guidelines in oncology |journal=Journal of the National Comprehensive Cancer Network |volume=4 |issue=8 |pages=776–818 |date=September 2006 |pmid=16948956 |doi= 10.6004/jnccn.2006.0068}}</ref> === Immunotherapy === {{Main|Cancer immunotherapy}} A variety of therapies using [[Cancer immunotherapy|immunotherapy]], stimulating or helping the [[immune system]] to fight cancer, have come into use since 1997. Approaches include:<ref>{{cite journal |vauthors=Waldmann TA |date=March 2003 |title=Immunotherapy: past, present and future |url=https://zenodo.org/record/1233435 |journal=Nature Medicine |volume=9 |issue=3 |pages=269–77 |doi=10.1038/nm0303-269 |pmid=12612576 |s2cid=9745527 |doi-access=free}}</ref> * [[Monoclonal antibody therapy]] * [[Checkpoint therapy]] (therapy that targets the [[immune checkpoint]]s or regulators of the [[immune system]]) * [[Adoptive cell transfer]] === Laser therapy === {{Main|Lasers in cancer treatment}} [[Laser]] therapy uses high-intensity light to treat cancer by shrinking or destroying tumors or precancerous growths. Lasers are most commonly used to treat superficial cancers that are on the surface of the body or the lining of internal organs. It is used to treat basal cell skin cancer and the very early stages of others like cervical, penile, vaginal, vulvar, and non-small cell lung cancer. It is often combined with other treatments, such as surgery, chemotherapy, or radiation therapy. [[Laser ablation|Laser-induced interstitial thermotherapy]] (LITT), or interstitial laser [[Laser coagulation|photocoagulation]], uses lasers to treat some cancers using hyperthermia, which uses heat to shrink tumors by damaging or killing cancer cells. Laser are more precise than surgery and cause less damage, pain, bleeding, swelling, and scarring. A disadvantage is that surgeons must have specialized training. It may be more expensive than other treatments.<ref name="NIHlaser">{{cite web|url=https://www.cancer.gov/about-cancer/treatment/types/surgery/lasers-fact-sheet|title=Lasers in Cancer Treatment|date=13 September 2011|publisher=National Institutes of Health, National Cancer Institute|access-date=15 December 2017}}{{PD-notice}}</ref> === Alternative medicine === [[Alternative cancer treatments|Complementary and alternative cancer treatments]] are a diverse group of therapies, practices and products that are not part of conventional medicine.<ref name="mnalt">{{cite journal |vauthors=Cassileth BR, Deng G |title=Complementary and alternative therapies for cancer |journal=The Oncologist |volume=9 |issue=1 |pages=80–89 |year=2004 |pmid=14755017 |doi=10.1634/theoncologist.9-1-80|s2cid=6453919 |url=http://theoncologist.alphamedpress.org/content/9/1/80.full.pdf }}</ref> "Complementary medicine" refers to methods and substances used along with conventional medicine, while "alternative medicine" refers to compounds used instead of conventional medicine.<ref>[http://nccam.nih.gov/health/whatiscam/#2 What Is CAM?] {{webarchive|url=https://web.archive.org/web/20051208040402/http://nccam.nih.gov/health/whatiscam/ |date=8 December 2005 }} [[National Center for Complementary and Alternative Medicine]]. Retrieved 3 February 2008.</ref> Most complementary and alternative medicines for cancer have not been studied or tested using conventional techniques such as clinical trials. Some alternative treatments have been investigated and shown to be ineffective but still continue to be marketed and promoted. Cancer researcher Andrew J. Vickers stated, "The label 'unproven' is inappropriate for such therapies; it is time to assert that many alternative cancer therapies have been 'disproven'."<ref name="pmid15061600">{{cite journal |vauthors=Vickers A |title=Alternative cancer cures: "unproven" or "disproven"? |journal=CA: A Cancer Journal for Clinicians |volume=54 |issue=2 |pages=110–18 |year=2004 |pmid=15061600 |doi=10.3322/canjclin.54.2.110|citeseerx=10.1.1.521.2180 |s2cid=35124492 }}</ref> == Prognosis == {{See also|Cancer survival rates|List of cancer mortality rates in the United States|Cancer survivor}} [[File:Three measures of cancer mortality, OWID.svg|thumb|upright=1.15|Three measures of global cancer mortality from 1990 to 2017<ref>{{cite web |title=Three measures of cancer mortality |url=https://ourworldindata.org/grapher/cancer-deaths-rate-and-age-standardized-rate-index |website=Our World in Data |access-date=7 March 2020}}</ref>]] Survival rates vary by cancer type and by the stage at which it is diagnosed, ranging from majority survival to complete mortality five years after diagnosis. Once a cancer has metastasized, prognosis normally becomes much worse. About half of patients receiving treatment for invasive cancer (excluding [[carcinoma in situ|carcinoma ''in situ'']] and non-melanoma skin cancers) die from that cancer or its treatment.<ref name=Epi11/> A majority of cancer deaths are due to metastases of the primary tumor.<ref>{{cite journal | vauthors = Tammela T, Sage J | title = Investigating Tumor Heterogeneity in Mouse Models | journal = Annual Review of Cancer Biology | volume = 4 | issue = 1 | pages = 99–119 | date = March 2020 | pmid = 34164589 | pmc = 8218894 | doi = 10.1146/annurev-cancerbio-030419-033413 | doi-access = free }}</ref> Survival is worse in the [[developing world]],<ref name=Epi11/> partly because the types of cancer that are most common there are harder to treat than those associated with [[developed countries]].<ref>{{cite book |title=World Cancer Report 2014 |date=2014 |publisher=World Health Organization |isbn=978-92-832-0429-9 |url=http://www.searo.who.int/publications/bookstore/documents/9283204298/en/ |page=22 |archive-url=https://web.archive.org/web/20170712114430/http://www.searo.who.int/publications/bookstore/documents/9283204298/en/ |archive-date=12 July 2017}}</ref> Those who survive cancer develop a second primary cancer at about twice the rate of those never diagnosed.<ref name=isbn1-55009-213-8/> The increased risk is believed to be due to the random chance of developing any cancer, the likelihood of surviving the first cancer, the same risk factors that produced the first cancer, unwanted side effects of treating the first cancer (particularly radiation therapy), and better compliance with screening.<ref name="isbn1-55009-213-8">{{cite book | veditors = Frei E, Kufe DW, Holland JF | vauthors = Rheingold S, Neugut A, Meadows A | title = Holland-Frei Cancer Medicine | edition = 6th | publisher = BC Decker | location = Hamilton, Ont | year = 2003 | page = [https://archive.org/details/cancermedicine60002unse/page/2399 2399] | isbn = 978-1-55009-213-4 | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK20948/#A41087 | chapter = 156: Secondary Cancers: Incidence, Risk Factors, and Management | url = https://archive.org/details/cancermedicine60002unse/page/2399 }}</ref> Predicting short- or long-term survival depends on many factors. The most important are the cancer type and the patient's age and overall health. Those who are [[wikt:frailty|frail]] with other health problems have lower survival rates than otherwise healthy people. [[Centenarian]]s are unlikely to survive for five years even if treatment is successful. People who report a higher quality of life tend to survive longer.<ref>{{cite journal |vauthors=Montazeri A |title=Quality of life data as prognostic indicators of survival in cancer patients: an overview of the literature from 1982 to 2008 |journal=Health and Quality of Life Outcomes |volume=7 |page=102 |date=December 2009 |pmid=20030832 |pmc=2805623 |doi=10.1186/1477-7525-7-102 |author-link=Ali Montazeri |doi-access=free }}</ref> People with lower quality of life may be affected by [[major depressive disorder|depression]] and other complications and/or disease progression that both impairs quality and quantity of life. Additionally, patients with worse prognoses may be depressed or report poorer quality of life because they perceive that their condition is likely to be fatal.{{Citation needed|date=January 2025}} People with cancer have an increased risk of [[venous thromboembolism|blood clots in their veins]] which can be life-threatening.<ref name=":1">{{cite journal | vauthors = Akl EA, Kahale LA, Hakoum MB, Matar CF, Sperati F, Barba M, Yosuico VE, Terrenato I, Synnot A, Schünemann H | title = Parenteral anticoagulation in ambulatory patients with cancer | journal = The Cochrane Database of Systematic Reviews | volume = 2021 | pages = CD006652 | date = September 2017 | issue = 9 | pmid = 28892556 | pmc = 6419241 | doi = 10.1002/14651858.CD006652.pub5 }}</ref> The use of [[Anticoagulant|blood thinners]] such as [[heparin]] decrease the risk of blood clots but have not been shown to increase survival in people with cancer.<ref name=":1"/> People who take blood thinners also have an increased risk of bleeding.<ref name=":1"/> Although extremely rare, some forms of cancer, even from an advanced stage, can heal spontaneously. This phenomenon is known as [[spontaneous remission]].<ref>{{cite journal | vauthors = Radha G, Lopus M | title = The spontaneous remission of cancer: Current insights and therapeutic significance | journal = Translational Oncology | volume = 14 | issue = 9 | page = 101166 | date = September 2021 | pmid = 34242964 | pmc = 8271173 | doi = 10.1016/j.tranon.2021.101166 }}</ref> == Epidemiology == {{Main|Epidemiology of cancer}} {{See also|List of countries by cancer rate}} {{Image frame |width=520<!-- Must be kept at this size at this point (December 2017) --> |content ={{Global Heat Maps by Year| title=| table=Cancer death rate.tab| column=deaths| columnName=Deaths per 10,000| year=2017|%=}} |caption=Age-standardized death rate from cancer per 10,000 people.<ref>{{cite web |title=Cancer death rates |url=https://ourworldindata.org/grapher/cancer-death-rates |website=Our World in Data |access-date=4 October 2019}}</ref> |align=right }} Estimates are that in 2018, 18.1 million new cases of cancer and 9.6 million deaths occur globally.<ref name=IARC2018/> About 20% of males and 17% of females will get cancer at some point in time while 13% of males and 9% of females will die from it.<ref name=IARC2018>{{cite web |title=Latest global cancer data: Cancer burden rises to 18.1 million new cases and 9.6 million cancer deaths in 2018 |url=https://www.iarc.fr/wp-content/uploads/2018/09/pr263_E.pdf |website=iarc.fr |access-date=5 December 2018}}</ref> In 2008, approximately 12.7 million cancers were [[diagnosis|diagnosed]] (excluding [[non-melanoma skin cancer]]s and other non-invasive cancers)<ref name=Epi11/> and in 2010 nearly 7.98 million people died.<ref name=Loz2012>{{cite journal |vauthors=Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, Abraham J, Adair T, Aggarwal R, Ahn SY, Alvarado M, Anderson HR, Anderson LM, Andrews KG, Atkinson C, Baddour LM, Barker-Collo S, Bartels DH, Bell ML, Benjamin EJ, Bennett D, Bhalla K, Bikbov B, Bin Abdulhak A, Birbeck G, Blyth F, Bolliger I, Boufous S, Bucello C, Burch M, Burney P, Carapetis J, Chen H, Chou D, Chugh SS, Coffeng LE, Colan SD, Colquhoun S, Colson KE, Condon J, Connor MD, Cooper LT, Corriere M, Cortinovis M, de Vaccaro KC, Couser W, Cowie BC, Criqui MH, Cross M, Dabhadkar KC, Dahodwala N, De Leo D, Degenhardt L, Delossantos A, Denenberg J, Des Jarlais DC, Dharmaratne SD, Dorsey ER, Driscoll T, Duber H, Ebel B, Erwin PJ, Espindola P, Ezzati M, Feigin V, Flaxman AD, Forouzanfar MH, Fowkes FG, Franklin R, Fransen M, Freeman MK, Gabriel SE, Gakidou E, Gaspari F, Gillum RF, Gonzalez-Medina D, Halasa YA, Haring D, Harrison JE, Havmoeller R, Hay RJ, Hoen B, Hotez PJ, Hoy D, Jacobsen KH, James SL, Jasrasaria R, Jayaraman S, Johns N, Karthikeyan G, Kassebaum N, Keren A, Khoo JP, Knowlton LM, Kobusingye O, Koranteng A, Krishnamurthi R, Lipnick M, Lipshultz SE, Ohno SL, Mabweijano J, MacIntyre MF, Mallinger L, March L, Marks GB, Marks R, Matsumori A, Matzopoulos R, Mayosi BM, McAnulty JH, McDermott MM, McGrath J, Mensah GA, Merriman TR, Michaud C, Miller M, Miller TR, Mock C, Mocumbi AO, Mokdad AA, Moran A, Mulholland K, Nair MN, Naldi L, Narayan KM, Nasseri K, Norman P, O'Donnell M, Omer SB, Ortblad K, Osborne R, Ozgediz D, Pahari B, Pandian JD, Rivero AP, Padilla RP, Perez-Ruiz F, Perico N, Phillips D, Pierce K, Pope CA, Porrini E, Pourmalek F, Raju M, Ranganathan D, Rehm JT, Rein DB, Remuzzi G, Rivara FP, Roberts T, De León FR, Rosenfeld LC, Rushton L, Sacco RL, Salomon JA, Sampson U, Sanman E, Schwebel DC, Segui-Gomez M, Shepard DS, Singh D, Singleton J, Sliwa K, Smith E, Steer A, Taylor JA, Thomas B, Tleyjeh IM, Towbin JA, Truelsen T, Undurraga EA, Venketasubramanian N, Vijayakumar L, Vos T, Wagner GR, Wang M, Wang W, Watt K, Weinstock MA, Weintraub R, Wilkinson JD, Woolf AD, Wulf S, Yeh PH, Yip P, Zabetian A, Zheng ZJ, Lopez AD, Murray CJ, AlMazroa MA, Memish ZA | s2cid = 1541253 |title=Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010 |journal=Lancet |volume=380 |issue=9859 |pages=2095–128 |date=December 2012 |pmid=23245604 |doi=10.1016/S0140-6736(12)61728-0 | pmc = 10790329 |hdl=10536/DRO/DU:30050819| url = https://zenodo.org/record/2557786 |hdl-access=free }}</ref> Cancers account for approximately 16% of deaths. The most common {{as of|2018|lc=yes}} are lung cancer (1.76 million deaths), [[colorectal cancer]] (860,000) [[stomach cancer]] (780,000), [[liver cancer]] (780,000), and breast cancer (620,000).<ref name=WHO2018/> This makes invasive cancer the leading cause of death in the [[developed country|developed world]] and the second leading in the [[developing country|developing world]].<ref name=Epi11/> Over half of these cases occur in the developing world.<ref name=Epi11/> Deaths from cancer were 5.8 million in 1990.<ref name=Loz2012/> Deaths have been increasing primarily due to longer lifespans and lifestyle changes in the developing world.<ref name=Epi11/> The most significant [[Risk factor (epidemiology)|risk factor]] for developing cancer is age.<ref name=Coleman>{{cite book | vauthors = Coleman WB, Rubinas TC | veditors = Tsongalis GJ, Coleman WL | title = Molecular Pathology: The Molecular Basis of Human Disease | publisher = Elsevier Academic Press | location = Amsterdam | year = 2009 | page = 66 | chapter = 4 | chapter-url = {{google books |plainurl=y |id=7MaclAEA}} | isbn = 978-0-12-374419-7 }}{{dead link|date=July 2023 |bot=InternetArchiveBot |fix-attempted=yes }}</ref> Although it is possible for cancer to strike at any age, most patients with invasive cancer are over 65.<ref name=Coleman/> According to cancer researcher [[Robert Weinberg (biologist)|Robert A. Weinberg]], "If we lived long enough, sooner or later we all would get cancer."<ref name=Weinberg>{{cite news |url=https://www.nytimes.com/2010/12/28/health/28cancer.html |title=Unearthing Prehistoric Tumors, and Debate |newspaper=[[The New York Times]] |date=28 December 2010 | vauthors = Johnson G |url-status=live |archive-url=https://web.archive.org/web/20170624233156/http://www.nytimes.com/2010/12/28/health/28cancer.html |archive-date=24 June 2017}}</ref> Some of the association between aging and cancer is attributed to [[immunosenescence]],<ref>{{cite journal | vauthors = Pawelec G, Derhovanessian E, Larbi A | title = Immunosenescence and cancer | journal = Critical Reviews in Oncology/Hematology | volume = 75 | issue = 2 | pages = 165–72 | date = August 2010 | pmid = 20656212 | doi = 10.1016/j.critrevonc.2010.06.012 }}</ref> errors accumulated in [[DNA]] over a lifetime<ref>{{cite book |vauthors=Alberts B, Johnson A, Lewis J |title=Molecular biology of the cell |publisher=Garland Science |location=New York |year=2002 |edition=4th |chapter=The Preventable Causes of Cancer |isbn=978-0-8153-4072-0 |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK26897/ |quote=A certain irreducible background incidence of cancer is to be expected regardless of circumstances: mutations can never be absolutely avoided, because they are an inescapable consequence of fundamental limitations on the accuracy of DNA replication, as discussed in Chapter 5. If a human could live long enough, it is inevitable that at least one of his or her cells would eventually accumulate a set of mutations sufficient for cancer to develop. | display-authors = etal |url-status=live |archive-url=https://web.archive.org/web/20160102193148/http://www.ncbi.nlm.nih.gov/books/NBK26897/ |archive-date=2 January 2016}}</ref> and age-related changes in the [[endocrine system]].<ref>{{cite journal | vauthors = Anisimov VN, Sikora E, Pawelec G | s2cid = 17412298 | title = Relationships between cancer and aging: a multilevel approach | journal = Biogerontology | volume = 10 | issue = 4 | pages = 323–38 | date = August 2009 | pmid = 19156531 | doi = 10.1007/s10522-008-9209-8 }}</ref> Aging's effect on cancer is complicated by factors such as DNA damage and inflammation promoting it and factors such as vascular aging and endocrine changes inhibiting it.<ref>{{cite journal | vauthors = de Magalhães JP | s2cid = 5726826 | title = How ageing processes influence cancer | journal = Nature Reviews. Cancer | volume = 13 | issue = 5 | pages = 357–65 | date = May 2013 | pmid = 23612461 | doi = 10.1038/nrc3497 }}</ref> Some slow-growing cancers are particularly common, but often are not fatal. [[Autopsy]] studies in Europe and Asia showed that up to 36% of people have undiagnosed and apparently harmless [[thyroid cancer]] at the time of their deaths and that 80% of men develop [[prostate cancer]] by age 80.<ref>{{cite book | vauthors = David S, Fraumeni JF |title=Cancer Epidemiology and Prevention |url={{google books |plainurl=y |id=qfN8Y1_lbDYC |page=977}}|date=24 August 2006|publisher=Oxford University Press|isbn=978-0-19-974797-9|page=977}}</ref><ref>{{cite book | vauthors = Bostwick DG, Eble JN |title=Urological Surgical Pathology |publisher=Mosby |location=St. Louis |year=2007 |page=468 |isbn=978-0-323-01970-5 |url={{google books |plainurl=y |id=z7AA-DS0VegC |page=335}}}}</ref> As these cancers do not cause the patient's death, identifying them would have represented [[overdiagnosis]] rather than useful medical care.{{Citation needed|date=January 2025}} The three most common [[childhood cancer]]s are [[leukemia]] (34%), [[brain tumor]]s (23%) and [[lymphoma]]s (12%).<ref name=Euro10>{{cite journal | vauthors = Kaatsch P | title = Epidemiology of childhood cancer | journal = Cancer Treatment Reviews | volume = 36 | issue = 4 | pages = 277–285 | date = June 2010 | pmid = 20231056 | doi = 10.1016/j.ctrv.2010.02.003 }}</ref> In the United States cancer affects about 1 in 285 children.<ref name=Eli2014>{{cite journal | vauthors = Ward E, DeSantis C, Robbins A, Kohler B, Jemal A | title = Childhood and adolescent cancer statistics, 2014 | journal = CA | volume = 64 | issue = 2 | pages = 83–103 | date = January 2014 | pmid = 24488779 | doi = 10.3322/caac.21219 | s2cid = 34364885 | doi-access = free }}</ref> Rates of childhood cancer increased by 0.6% per year between 1975 and 2002 in the United States<ref>{{cite journal | vauthors = Ward EM, Thun MJ, Hannan LM, Jemal A | title = Interpreting cancer trends | journal = Annals of the New York Academy of Sciences | volume = 1076 | issue = 1 | pages = 29–53 | date = September 2006 | pmid = 17119192 | doi = 10.1196/annals.1371.048 | s2cid = 1579801 | bibcode = 2006NYASA1076...29W }}</ref> and by 1.1% per year between 1978 and 1997 in Europe.<ref name=Euro10/> Death from childhood cancer decreased by half between 1975 and 2010 in the United States.<ref name=Eli2014/> == History == {{Main|History of cancer}} [[File:Clara Jacobi-Tumor.jpg|thumb|left|[[Engraving]] with two views of a Dutch woman who had a tumor removed from her neck in 1689]] Cancer has existed for all of human history.<ref name=Hist1/> The earliest written record regarding cancer is from {{circa|1600 BC}} in the Egyptian [[Edwin Smith Papyrus]] and describes breast cancer.<ref name=Hist1>{{cite journal |vauthors=Hajdu SI |s2cid=39667103 |title=A note from history: landmarks in history of cancer, part 1 |journal=Cancer |volume=117 |issue=5 |pages=1097–102 |date=March 2011 |pmid=20960499 |doi=10.1002/cncr.25553|doi-access=free }}</ref> [[Hippocrates]] ({{circa|460 BC|370 BC}}) described several kinds of cancer, referring to them with the [[Greek language|Greek]] word [[wikt:καρκίνος#Ancient Greek|καρκίνος]] ''karkinos'' (crab or [[crayfish]]).<ref name=Hist1/> This name comes from the appearance of the cut surface of a solid malignant tumor, with "the veins stretched on all sides as the animal the crab has its feet, whence it derives its name".<ref>Paul of Aegina, 7th century AD, quoted in {{cite web | vauthors = Moss RW |title=Galen on Cancer |url=http://www.cancerdecisions.com/speeches/galen1989.html |archive-url=https://web.archive.org/web/20110716111312/http://www.cancerdecisions.com/speeches/galen1989.html |archive-date=16 July 2011 |publisher=CancerDecisions |year=2004 }} Referenced from Michael Shimkin, Contrary to Nature, Washington, DC: Superintendent of Document, DHEW Publication No. (NIH) 79–720, p. 35.</ref> [[Galen]] stated that "cancer of the breast is so called because of the fancied resemblance to a crab given by the lateral prolongations of the tumor and the adjacent distended veins".<ref name="Majno2004">{{cite book | vauthors = Majno G, Joris I |title=Cells, Tissues, and Disease: Principles of General Pathology: Principles of General Pathology |url={{google books |plainurl=y |id=8yAf6U7njlcC |page=738}}|access-date=11 September 2013|date=12 August 2004|publisher=Oxford University Press|isbn=978-0-19-974892-1}}</ref>{{rp|738}} [[Aulus Cornelius Celsus|Celsus]] ({{circa|25 BC}} – 50 AD) translated ''karkinos'' into the [[Latin]] ''cancer'', also meaning crab and recommended surgery as treatment.<ref name=Hist1/> [[Galen]] (2nd century AD) disagreed with the use of surgery and recommended [[purgatives]] instead.<ref name=Hist1/> These recommendations largely stood for 1000 years.<ref name=Hist1/> In the 15th, 16th and 17th centuries, it became acceptable for doctors to [[dissection|dissect bodies]] to discover the cause of death.<ref name=Hist2>{{cite journal |vauthors=Hajdu SI |s2cid=28148111 |title=A note from history: landmarks in history of cancer, part 2 |journal=Cancer |volume=117 |issue=12 |pages=2811–20 |date=June 2011 |pmid=21656759 |doi=10.1002/cncr.25825|doi-access=free }}</ref> The German professor [[Wilhelm Fabry]] believed that breast cancer was caused by a milk clot in a mammary duct. The Dutch professor [[Francois de la Boe Sylvius]], a follower of [[René Descartes|Descartes]], believed that all disease was the outcome of chemical processes and that acidic [[lymph]] fluid was the cause of cancer. His contemporary [[Nicolaes Tulp]] believed that cancer was a poison that slowly spreads and concluded that it was [[infectious disease|contagious]].<ref>{{cite book | vauthors = Yalom M |title=A history of the breast |year=1998 |publisher=Ballantine Books |location=New York |isbn=978-0-679-43459-7 |url={{google books |plainurl=y |id=FFX1U3KUjPsC}}|edition=1}}</ref> The physician John Hill described [[tobacco sniffing]] as the cause of nose cancer in 1761.<ref name=Hist2/> This was followed by the report in 1775 by British surgeon [[Percivall Pott]] that [[chimney sweeps' carcinoma]], a cancer of the [[scrotum]], was a common disease among [[chimney sweep]]s.<ref>{{cite journal |vauthors=Hajdu SI |title=A note from history: landmarks in history of cancer, part 3 |journal=Cancer |volume=118 |issue=4 |pages=1155–68 |date=February 2012 |pmid=21751192 |doi=10.1002/cncr.26320|s2cid=38892895 |doi-access=free }}</ref> With the widespread use of the microscope in the 18th century, it was discovered that the 'cancer poison' spread from the primary tumor through the lymph nodes to other sites ("[[metastasis]]"). This view of the disease was first formulated by the English surgeon [[Campbell De Morgan]] between 1871 and 1874.<ref>{{cite journal | vauthors = Grange JM, Stanford JL, Stanford CA | title = Campbell De Morgan's 'Observations on cancer', and their relevance today | journal = Journal of the Royal Society of Medicine | volume = 95 | issue = 6 | pages = 296–299 | date = June 2002 | pmid = 12042378 | pmc = 1279913 | doi = 10.1177/014107680209500609 }}</ref> == Society and culture == Although many diseases (such as heart failure) may have a worse prognosis than most cases of cancer, cancer is the subject of widespread fear and taboos. The [[euphemism]] of "a long illness" to describe cancers leading to death is still commonly used in obituaries, rather than naming the disease explicitly, reflecting an apparent [[social stigma|stigma]].<ref>{{Cite news | vauthors = Barbara E |author-link=Barbara Ehrenreich |title=Welcome to Cancerland |newspaper=[[Harper's Magazine]] |date=November 2001 |issn=0017-789X |url=http://www.barbaraehrenreich.com/cancerland.htm |archive-url=https://web.archive.org/web/20131108181820/http://www.barbaraehrenreich.com/cancerland.htm |archive-date=8 November 2013}}</ref> Cancer is also euphemised as "the C-word";<ref>{{cite journal | vauthors = Pozorski A |s2cid=160969212 |title=Confronting the "C" Word: Cancer and Death in Philip Roth's Fiction |journal=Philip Roth Studies |date=20 March 2015 |volume=11 |issue=1 |pages=105–123 |doi=10.5703/philrothstud.11.1.105 |url=https://muse.jhu.edu/article/577333/pdf |access-date=13 April 2020 |language=en |issn=1940-5278}}</ref><ref>{{cite news | vauthors = Wollaston S |title=The C-Word review – a wonderful testament to a woman who faced cancer with honesty, verve and wit |url=https://www.theguardian.com/tv-and-radio/2015/may/04/the-c-word-review-sheridan-smith-cancer-wonderful-testament |access-date=13 April 2020 |work=The Guardian |date=4 May 2015}}</ref><ref>{{cite news |title=Avoiding the 'C' Word for Low-Risk Thyroid Cancer |url=https://www.medscape.com/viewarticle/901265 |access-date=13 April 2020 |work=Medscape}}</ref> [[Macmillan Cancer Support]] uses the term to try to lessen the fear around the disease.<ref>{{cite news |title=The C word: how we react to cancer today |url=https://www.networks.nhs.uk/news/the-c-word-how-we-react-to-cancer-today |website=NHS Networks |access-date=13 April 2020 |language=en-gb |archive-date=22 October 2020 |archive-url=https://web.archive.org/web/20201022210915/https://www.networks.nhs.uk/news/the-c-word-how-we-react-to-cancer-today }}</ref> In Nigeria, one local name for cancer translates into English as "the disease that cannot be cured".<ref name=":0">{{Cite book|url=https://books.google.com/books?id=Tmrp7dkvJk4C&pg=PA196|title=Handbook of Psychiatry in Palliative Medicine| vauthors = Chochinov HM, Breitbart W |date=2009|publisher=Oxford University Press|isbn=978-0-19-530107-6|page=196|language=en}}</ref> This deep belief that cancer is necessarily a difficult and usually deadly disease is reflected in the systems chosen by society to compile cancer statistics: the most common form of cancer—non-melanoma [[skin cancer]]s, accounting for about one-third of cancer cases worldwide, but very few deaths<ref name="Bolognia">{{cite book | vauthors = Rapini RP, Bolognia JL, Jorizzo JL |title=Dermatology: 2-Volume Set |publisher=Mosby |location=St. Louis |year=2007 |isbn=978-1-4160-2999-1 }}</ref><ref>{{cite web |title=Skin cancers |url=https://www.who.int/uv/faq/skincancer/en/index1.html |publisher=World Health Organization |access-date=19 January 2011 |url-status=live |archive-url=https://web.archive.org/web/20100927065836/http://www.who.int/uv/faq/skincancer/en/index1.html |archive-date=27 September 2010}}</ref>—are excluded from cancer statistics specifically because they are easily treated and almost always cured, often in a single, short, outpatient procedure.<ref>{{cite book | vauthors = McCulley M, Greenwell P |title=Molecular therapeutics: 21st-century medicine |publisher=J. Wiley |location=London |year=2007 |page=207 |url={{google books |plainurl=y |id=aG3SNAEACAAJ0470019166}} |isbn=978-0-470-01916-0 }}{{dead link|date=July 2023 |bot=InternetArchiveBot |fix-attempted=yes }}</ref> Western conceptions of [[patients' rights]] for people with cancer include a duty to fully disclose the medical situation to the person, and the right to engage in [[Shared decision-making in medicine|shared decision-making]] in a way that respects the person's own values. In other cultures, other rights and values are preferred. For example, most African cultures value whole families rather than [[individualism]]. In parts of Africa, a diagnosis is commonly made so late that cure is not possible, and treatment, if available at all, would quickly bankrupt the family. As a result of these factors, African healthcare providers tend to let family members decide whether, when and how to disclose the diagnosis, and they tend to do so slowly and circuitously, as the person shows interest and an ability to cope with the grim news.<ref name=":0"/> People from Asian and South American countries also tend to prefer a slower, less candid approach to disclosure than is idealized in the United States and Western Europe, and they believe that sometimes it would be preferable not to be told about a cancer diagnosis.<ref name=":0"/> In general, disclosure of the diagnosis is more common than it was in the 20th century, but full disclosure of the prognosis is not offered to many patients around the world.<ref name=":0"/> In the United States and some other [[Cultural differences in breast cancer diagnosis and treatment|cultures]], cancer is regarded as a disease that must be "fought" to end the "civil insurrection"; a [[War on Cancer]] was declared in the US. Military metaphors are particularly common in descriptions of cancer's human effects, and they emphasize both the state of the patient's health and the need to take immediate, decisive actions himself rather than to delay, to ignore or to rely entirely on others. The military metaphors also help rationalize radical, destructive treatments.<ref name="Gwyn">{{cite book | vauthors = Low G, Cameron L |title=Researching and Applying Metaphor |chapter-url={{google books |plainurl=y |id=8aOxMvo_ag8C}}|year=1999|publisher=Cambridge University Press|isbn=978-0-521-64964-3| chapter=10}}</ref><ref>{{cite book | vauthors = Sulik GA |title=Pink Ribbon Blues: How Breast Cancer Culture Undermines Women's Health |url={{google books |plainurl=y |id=_it2CwAAQBAJ |page=78}}|year=2010|publisher=Oxford University Press|isbn=978-0-19-974993-5|pages=78–89}}</ref> In the 1970s, a relatively popular [[alternative cancer treatment]] in the US was a specialized form of [[talk therapy]], based on the idea that cancer was caused by a bad attitude.<ref name=Olson/> People with a "cancer personality"—depressed, repressed, self-loathing and afraid to express their emotions—were believed to have manifested cancer through subconscious desire. Some psychotherapists claimed that treatment to change the patient's outlook on life would cure the cancer.<ref name=Olson/> Among other effects, this belief allowed society to [[Victim blaming|blame the victim]] for having caused the cancer (by "wanting" it) or having prevented its cure (by not becoming a sufficiently happy, fearless and loving person).<ref name=Ehrenreich/> It also increased patients' anxiety, as they incorrectly believed that natural emotions of sadness, anger or fear shorten their lives.<ref name=Ehrenreich/> The idea was ridiculed by [[Susan Sontag]], who published ''[[Illness as Metaphor]]'' while recovering from treatment for breast cancer in 1978.<ref name=Olson>{{cite book | vauthors = Olson JS |title=Bathsheba's Breast: Women, Cancer, and History |url={{google books |plainurl=y |id=gp9aMBieClMC |page=145}}|year=2005|publisher=JHU Press|isbn=978-0-8018-8064-3| pages = 145–70 | oclc = 186453370 }}</ref> Although the original idea is now generally regarded as nonsense, the idea partly persists in a reduced form with a widespread, but incorrect, belief that deliberately cultivating a habit of [[Optimism|positive thinking]] will increase survival.<ref name=Ehrenreich>{{cite book | vauthors = Ehrenreich B |author-link=Barbara Ehrenreich |title=Bright-sided: How the Relentless Promotion of Positive Thinking Has Undermined America |url={{google books |plainurl=y |id=wxJlvB7bCO4C |page=15}}|year=2009|publisher=Henry Holt and Company|isbn=978-0-8050-8749-9| pages = 15–44 }}</ref> This notion is particularly strong in [[breast cancer culture]].<ref name=Ehrenreich /> One idea about why people with cancer are blamed or stigmatized, called the [[just-world fallacy]], is that blaming cancer on the patient's actions or attitudes allows the blamers to regain a sense of control. This is based upon the blamers' belief that the world is fundamentally just and so any dangerous illness, like cancer, must be a type of punishment for bad choices, because in a just world, bad things would not happen to good people.<ref>{{Cite news |title=A Sick Stigma: Why are cancer patients blamed for their illness? |date=24 September 2013 |url=http://www.slate.com/articles/health_and_science/medical_examiner/2013/09/cancer_stigma_don_t_blame_patients_for_their_disease_no_matter_what_the.html |newspaper=Slate | vauthors = Huff C |url-status=live |archive-url=https://web.archive.org/web/20131011120507/http://www.slate.com/articles/health_and_science/medical_examiner/2013/09/cancer_stigma_don_t_blame_patients_for_their_disease_no_matter_what_the.html |archive-date=11 October 2013}}</ref> === Economic effect === The total health care expenditure on cancer in the US was estimated to be $80.2 billion in 2015.<ref>{{cite web |title=Economic Impact of Cancer |url=https://www.cancer.org/cancer/cancer-basics/economic-impact-of-cancer.html |website=American Cancer Society |date=3 January 2018 |access-date=5 July 2018}}</ref> Even though cancer-related health care expenditure have increased in absolute terms during recent decades, the share of health expenditure devoted to cancer treatment has remained close to 5% between the 1960s and 2004.<ref>{{cite journal |vauthors=Bosanquet N, Sikora K |title=The economics of cancer care in the UK |journal=Lancet Oncology |volume=5 |issue=9 |pages=568–74 |year=2004 |pmid=15337487 |doi=10.1016/S1470-2045(04)01569-4}}</ref><ref>{{cite journal |vauthors=Mariotto AB, Yabroff KR, Shao Y, Feuer EJ, Brown ML |title=Projections of the cost of cancer care in the United States: 2010–2020 |journal=Journal of the National Cancer Institute |volume=103 |issue=2 |pages=117–28 |year=2011 |pmid=21228314 |pmc=3107566 |doi=10.1093/jnci/djq495}}</ref> A similar pattern has been observed in Europe where about 6% of all health care expenditure are spent on cancer treatment.<ref>{{cite journal |vauthors=Jönsson B, Hofmarcher T, Lindgren P, Wilking N |title=The cost and burden of cancer in the European Union 1995–2014 |journal=European Journal of Cancer |volume=66 |issue=Oct |pages=162–70 |year=2016 |pmid=27589247 |doi=10.1016/j.ejca.2016.06.022}}</ref><ref name=EJC2018>{{cite journal |vauthors=Hofmarcher T, Lindgren P, Wilking N, Jönsson B |title=The cost of cancer in Europe 2018 |journal=European Journal of Cancer |volume=129 |issue=Apr |pages=41–49 |year=2020 |pmid=32120274 |doi=10.1016/j.ejca.2020.01.011|doi-access=free }}</ref> In addition to health care expenditure and [[financial toxicity]], cancer causes indirect costs in the form of productivity losses due to sick days, permanent incapacity and disability as well as premature death during working age. Cancer causes also costs for informal care. Indirect costs and informal care costs are typically estimated to exceed or equal the health care costs of cancer.<ref>{{cite journal |vauthors=Luengo-Fernandez R, Leal J, Gray A, Sullivan R |title=Economic burden of cancer across the European Union: a population-based cost analysis |journal=Lancet Oncology |volume=14 |issue=12 |pages=1165–74 |year=2013 |pmid=24131614 |doi=10.1016/S1470-2045(13)70442-X}}</ref><ref name=EJC2018 /> === Workplace === In the United States, cancer is included as a protected condition by the [[Equal Employment Opportunity Commission]] (EEOC), mainly due to the potential for cancer having discriminating effects on workers.<ref name="EEOC">U.S. Equal Employment Opportunity Commission. "Questions & Answers about Cancer in the Workplace and the Americans with Disabilities Act (ADA)." https://www.eeoc.gov/laws/types/cancer.cfm</ref> Discrimination in the workplace could occur if an employer holds a false belief that a person with cancer is not capable of doing a job properly, and may ask for more [[sick leave]] than other employees. Employers may also make hiring or firing decisions based on misconceptions about cancer disabilities, if present. The EEOC provides interview guidelines for employers, as well as lists of possible solutions for assessing and accommodating employees with cancer.<ref name="EEOC" /> === Effect on divorce === A study found women were around six times more likely to be [[divorced]] soon after a diagnosis of cancer compared to men.<ref>{{cite journal | vauthors = Glantz MJ, Chamberlain MC, Liu Q, Hsieh CC, Edwards KR, Van Horn A, Recht L | title = Gender disparity in the rate of partner abandonment in patients with serious medical illness | journal = Cancer | volume = 115 | issue = 22 | pages = 5237–5242 | date = November 2009 | pmid = 19645027 | doi = 10.1002/cncr.24577 }}</ref> Rate of separation for cancer-survivors showed correlations with race, age, income, and [[comorbidity|comorbidities]] in a study.<ref>{{cite journal | vauthors = Stephens C, Westmaas JL, Kim J, Cannady R, Stein K | title = Gender differences in associations between cancer-related problems and relationship dissolution among cancer survivors | journal = Journal of Cancer Survivorship | volume = 10 | issue = 5 | pages = 865–873 | date = October 2016 | pmid = 26995006 | doi = 10.1007/s11764-016-0532-9 }}</ref> A review found a somewhat decreased divorce rate for most cancer types, and noted [[study heterogeneity]] and [[Methodology|methodological]] weaknesses for many studies on the effects of cancer on divorce.<ref>{{cite journal | vauthors = Fugmann D, Boeker M, Holsteg S, Steiner N, Prins J, Karger A | title = A Systematic Review: The Effect of Cancer on the Divorce Rate | journal = Frontiers in Psychology | volume = 13 | page = 828656 | date = 9 March 2022 | pmid = 35356338 | pmc = 8959852 | doi = 10.3389/fpsyg.2022.828656 | doi-access = free }}</ref> == Research == {{Main|Cancer research}} [[File:UF CancerHospital.JPG|thumb|upright=1.35|[[University of Florida Cancer Hospital]]]] Because cancer is a class of diseases,<ref name=WhatIsCancerNCI>{{cite web |url=https://www.cancer.gov/about-cancer/understanding/what-is-cancer |title=What Is Cancer? |publisher=[[National Cancer Institute]] |access-date=28 March 2018|date=17 September 2007}}</ref><ref>{{cite web |url=http://www.atsdr.cdc.gov/COM/cancer-fs.html |title=Cancer Fact Sheet |publisher=Agency for Toxic Substances & Disease Registry |date=30 August 2002 |access-date=17 August 2009 |archive-url=https://web.archive.org/web/20090813142933/http://www.atsdr.cdc.gov/COM/cancer-fs.html |archive-date=13 August 2009}}</ref> it is unlikely that there will ever be a single "[[cure for cancer]]" any more than there will be a single treatment for all [[infectious disease]]s.<ref>{{cite web |url=http://www.livescience.com/health/060919_bad_cancer.html |title=Exciting New Cancer Treatments Emerge Amid Persistent Myths | vauthors = Wanjek C |website=[[Live Science]] |date=16 September 2006 |access-date=17 August 2009 |url-status=live |archive-url=https://web.archive.org/web/20080516080512/http://www.livescience.com/health/060919_bad_cancer.html |archive-date=16 May 2008}}</ref> [[Angiogenesis inhibitor]]s were once incorrectly thought to have potential as a "[[silver bullet]]" treatment applicable to many types of cancer.<ref>{{cite journal |vauthors=Hayden EC |title=Cutting off cancer's supply lines |journal=Nature |volume=458 |issue=7239 |pages=686–87 |date=April 2009 |pmid=19360048 |doi=10.1038/458686b|doi-access=free }}</ref> Angiogenesis inhibitors and other cancer therapeutics are used in combination to reduce cancer morbidity and mortality.<ref>{{cite journal |vauthors=Bagri A, Kouros-Mehr H, Leong KG, Plowman GD |title=Use of anti-VEGF adjuvant therapy in cancer: challenges and rationale |journal=Trends in Molecular Medicine |volume=16 |issue=3 |pages=122–32 |date=March 2010 |pmid=20189876 |doi=10.1016/j.molmed.2010.01.004}}</ref> [[Experimental cancer treatment]]s are studied in [[clinical trial]]s to compare the proposed treatment to the best existing treatment. Treatments that succeeded in one cancer type can be tested against other types.<ref>{{cite journal |vauthors=Sleigh SH, Barton CL |s2cid=25267555 |title=Repurposing Strategies for Therapeutics |journal=Pharmaceutical Medicine|volume=24 |issue=3 |pages=151–59 |year=2010 |doi=10.1007/BF03256811 }}</ref> Diagnostic tests are under development to better target the right therapies to the right patients, based on their individual biology.<ref>{{cite journal |vauthors=Winther H, Jorgensen JT |s2cid=43505621 |title=Drug-Diagnostic Co-Development in Cancer |journal=Pharmaceutical Medicine |volume=24 |issue=6 |pages=363–75 |year=2010 |doi=10.1007/BF03256837 }}</ref> Cancer research focuses on the following issues: * Agents (e.g. viruses) and events (e.g. mutations) that cause or facilitate genetic changes in cells destined to become cancer. * The precise nature of the genetic damage and the genes that are affected by it. * The consequences of those genetic changes on the biology of the cell, both in generating the defining properties of a cancer cell and in facilitating additional genetic events that lead to further progression of the cancer. The improved understanding of [[molecular biology]] and [[cell biology|cellular biology]] due to cancer research has led to new treatments for cancer since US President [[Richard Nixon]] declared the "[[War on Cancer]]" in 1971. Since then, the country has spent over $200 billion on cancer research, including resources from public and private sectors.<ref>{{cite web | vauthors = Begley S |url=http://www.newsweek.com/id/157548/page/2 |title=Rethinking the War on Cancer |date=16 September 2008 |website=Newsweek |access-date=8 September 2008 |archive-url=https://web.archive.org/web/20080910012446/http://www.newsweek.com/id/157548/page/2 |archive-date=10 September 2008}}</ref> The cancer death rate (adjusting for size and age of the population) declined by five percent between 1950 and 2005.<ref name="24cancer">{{cite news |url=https://www.nytimes.com/2009/04/24/health/policy/24cancer.html |url-access=subscription |title=Advances Elusive in the Drive to Cure Cancer | vauthors = Kolata G |date=23 April 2009 |work=[[The New York Times]] |access-date=5 May 2009 |url-status=live |archive-url=https://web.archive.org/web/20120114120509/http://www.nytimes.com/2009/04/24/health/policy/24cancer.html |archive-date=14 January 2012}}</ref> Competition for financial resources appears to have suppressed the creativity, cooperation, risk-taking and original thinking required to make fundamental discoveries, unduly favoring low-risk research into small incremental advancements over riskier, more innovative research. Other consequences of competition appear to be many studies with dramatic claims whose results cannot be replicated and perverse incentives that encourage grantee institutions to grow without making sufficient investments in their own faculty and facilities.<ref>{{cite journal | vauthors = Alberts B, Kirschner MW, Tilghman S | author-link1 = Bruce Alberts | author-link4 = Harold Varmus |year=2014 |title=Rescuing US biomedical research from its systemic flaws |bibcode-access=free |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=111 |issue=16 |pages=5773–77 |doi=10.1073/pnas.1404402111 |pmid=24733905 |pmc=4000813|bibcode=2014PNAS..111.5773A |doi-access=free }}</ref><ref name=24cancer/><ref>{{cite news |url=https://www.nytimes.com/2009/06/28/health/research/28cancer.html |url-access=subscription |title=Grant System Leads Cancer Researchers to Play It Safe | vauthors = Kolata G |date=27 June 2009 |work=The New York Times |access-date=29 December 2009 |url-status=live |archive-url=https://web.archive.org/web/20110608133344/http://www.nytimes.com/2009/06/28/health/research/28cancer.html |archive-date=8 June 2011}}</ref><ref>{{cite journal | vauthors = Powell K |s2cid=4465686 |year=2016 |title=Young, talented and fed-up: scientists tell their stories |journal=Nature |volume=538 |issue= 7626|pages=446–49 |doi=10.1038/538446a |pmid=27786221|bibcode=2016Natur.538..446P |doi-access=free }}</ref> [[Virotherapy]], which uses convert viruses, is being studied.{{Citation needed|date=January 2025}} In the wake of the [[COVID-19]] pandemic, there has been a worry that cancer research and treatment are slowing down.<ref>{{Cite web|url=https://www.nbcnews.com/think/opinion/covid-s-impact-cancer-care-turning-oncologists-worst-fears-reality-ncna1257743|title = Opinion | I'm an oncologist. My worst fears about Covid and cancer are coming true|website = [[NBC News]]| date=12 February 2021 }}</ref><ref>{{Cite web|url=https://www.nydailynews.com/opinion/ny-oped-dont-sacrifice-cancer-care-to-covid-20210113-nesit6kuunfenpjcl2lpo2ftny-story.html|title=Don't sacrifice cancer care to COVID|website=[[New York Daily News]]|date=13 January 2021 }}</ref> On 2 December 2023, [[Nano Today]] published a groundbreaking discovery involving "NK cell-engaging nanodrones" for targeted cancer treatment. The development of "NK cell-engaging nanodrones" represents a significant leap forward in cancer treatment, showcasing how cutting-edge nanotechnology and immunotherapy can be combined to target and eliminate cancer cells with unprecedented precision. These nanodrones are designed to harness the power of natural killer (NK) cells, which play a crucial role in the body's immune response against tumors. By directing these NK cells specifically to the sites of tumors, the nanodrones can effectively concentrate the immune system's attack on the cancer cells, potentially leading to better outcomes for patients.<ref name=":2"/> The key innovation here lies in the use of protein cage nanoparticle-based systems. These systems are engineered to carry signals that attract NK cells directly to the tumor, overcoming one of the major challenges in cancer immunotherapy: ensuring that the immune cells find and attack only the cancer cells without harming healthy tissue. This targeted approach not only increases the efficacy of the treatment but also minimizes side effects, a common concern with broader-acting cancer therapies.<ref name=":2">{{Cite web |title=Revolutionary nanodrones enable targeted cancer treatment |url=https://www.sciencedaily.com/releases/2023/12/231229164725.htm |access-date=2024-03-24 |website=ScienceDaily |language=en}}</ref> == Pregnancy == Cancer affects approximately 1 in 1,000 pregnant women. The most common cancers found during pregnancy are the same as the most common cancers found in non-pregnant women during childbearing ages: breast cancer, cervical cancer, leukemia, lymphoma, melanoma, ovarian cancer and colorectal cancer.<ref name=yarbro/> Diagnosing a new cancer in a pregnant woman is difficult, in part because any symptoms are commonly assumed to be a normal discomfort associated with pregnancy. As a result, cancer is typically discovered at a somewhat later stage than average. Some imaging procedures, such as [[Magnetic resonance imaging|MRIs]] (magnetic resonance imaging), [[CT scan]]s, ultrasounds and [[mammography|mammograms]] with fetal shielding are considered safe during pregnancy; some others, such as [[Positron emission tomography|PET scans]], are not.<ref name=yarbro/> Treatment is generally the same as for non-pregnant women. However, radiation and radioactive drugs are normally avoided during pregnancy, especially if the fetal dose might exceed 100 cGy. In some cases, some or all treatments are postponed until after birth if the cancer is diagnosed late in the pregnancy. Early deliveries are often used to advance the start of treatment. Surgery is generally safe, but pelvic surgeries during the first trimester may cause miscarriage. Some treatments, especially certain chemotherapy drugs given during the [[first trimester]], increase the risk of [[birth defect]]s and pregnancy loss (spontaneous abortions and stillbirths).<ref name=yarbro/> Elective abortions are not required and, for the most common forms and stages of cancer, do not improve the mother's survival. In a few instances, such as advanced uterine cancer, the pregnancy cannot be continued and in others, the patient may end the pregnancy so that she can begin aggressive chemotherapy.<ref name=yarbro/> Some treatments can interfere with the mother's ability to give birth vaginally or to breastfeed.<ref name=yarbro/> Cervical cancer may require birth by [[Caesarean section]]. Radiation to the breast reduces the ability of that breast to produce milk and increases the risk of [[mastitis]]. Also, when chemotherapy is given after birth, many of the drugs appear in breast milk, which could harm the baby.<ref name=yarbro>{{cite book | vauthors = Yarbro CH, Wujcik D, Gobel BH |title=Cancer Nursing: Principles and Practice |url={{google books |plainurl=y |id=LJVTQs4QjJ0C |page=901}}|year=2010|publisher=Jones & Bartlett Learning|isbn=978-0-7637-6357-2|pages = 901–905}}</ref> == Other animals == [[Veterinary oncology]], concentrating mainly on cats and dogs, is a growing specialty in wealthy countries and the major forms of human treatment such as surgery and radiotherapy may be offered. The most common types of cancer differ, but the cancer burden seems at least as high in pets as in humans. Animals, typically rodents, are often used in cancer research and studies of natural cancers in larger animals may benefit research into human cancer.<ref>{{cite journal | vauthors = Thamm D |title=How companion animals contribute to the fight against cancer in humans |journal=Veterinaria Italiana |date=March 2009 |volume=54 |issue=1 |pages=111–20 |pmid=20391394 |url=http://www.izs.it/vet_italiana/2009/45_1/111.pdf |access-date=18 July 2014 |url-status=live |archive-url=https://web.archive.org/web/20140723044907/http://www.izs.it/vet_italiana/2009/45_1/111.pdf |archive-date=23 July 2014}}</ref> Across wild animals, there is still limited data on cancer. Nonetheless, a study published in 2022, explored cancer risk in (non-domesticated) zoo mammals, belonging to 191 species, 110,148 individual, demonstrated that cancer is a ubiquitous disease of mammals and it can emerge anywhere along the mammalian phylogeny.<ref>{{cite journal | vauthors = Vincze O, Colchero F, Lemaître JF, Conde DA, Pavard S, Bieuville M, Urrutia AO, Ujvari B, Boddy AM, Maley CC, Thomas F, Giraudeau M | title = Cancer risk across mammals | journal = Nature | volume = 601 | issue = 7892 | pages = 263–267 | date = January 2022 | pmid = 34937938 | pmc = 8755536 | doi = 10.1038/s41586-021-04224-5 | s2cid = 245425871 | bibcode = 2022Natur.601..263V }}</ref> This research also highlighted that cancer risk is not uniformly distributed along mammals. For instance, species in the order [[Carnivora]] are particularly prone to be affected by cancer (e.g. over 25% of [[clouded leopard]]s, [[bat-eared fox]]es and [[red wolves]] die of cancer), while [[ungulate]]s (especially [[even-toed ungulate]]s) appear to face consistently low cancer risks.{{Citation needed|date=January 2025}} In non-humans, a few types of [[transmissible cancer]] have also been described, wherein the cancer spreads between animals by transmission of the tumor cells themselves. This phenomenon is seen in dogs with [[Sticker's sarcoma]] (also known as canine transmissible venereal tumor), and in [[Tasmanian devils]] with [[devil facial tumour disease]] (DFTD).<ref name="pmid16901782">{{cite journal |vauthors=Murgia C, Pritchard JK, Kim SY, Fassati A, Weiss RA |title=Clonal origin and evolution of a transmissible cancer |journal=Cell |volume=126 |issue=3 |pages=477–87 |date=August 2006 |pmid=16901782 |pmc=2593932 |doi=10.1016/j.cell.2006.05.051}}</ref> == See also == * [[Cancer screening]] * [[Cancer treatment]] * [[Causes of cancer]] * [[Epidemiology of cancer]] * [[Occupational cancer]] * [[Oncology]] * [[Metabolic theory of cancer]] == References == {{reflist}} == Further reading == {{refbegin}} * {{cite book | vauthors = Bast RC, Croe CM, Hait WN, Hong WK, Kufe DW, Piccart-Gebhart M, Pollock RE, Weichselbaum RR, Yang H, Holland JF |title=Holland-Frei Cancer Medicine |url={{google books |plainurl=y |id=onCBjwEACAAJ}} |year=2016 |publisher=Wiley |isbn=978-1-118-93469-2}} * {{cite book | vauthors = Kleinsmith LJ |title=Principles of cancer biology |url={{google books |plainurl=y |id=LKVrAAAAMAAJ}}|year=2006|publisher=Pearson Benjamin Cummings|isbn=978-0-8053-4003-7}} * {{cite book |last=Mukherjee |first=Siddhartha |author-link=Siddhartha Mukherjee |title=The Emperor of All Maladies: A Biography of Cancer |year=2010 |publisher=Simon & Schuster |isbn=978-1-4391-0795-9 |url=https://archive.org/details/emperorofallmala00mukh |access-date=7 August 2013 }} * {{cite book | vauthors = Pazdur R, Camphausen KA, Wagman LD, Hoskins WJ |title=Cancer Management: A Multidisciplinary Approach | year=2009 | publisher = Cmp United Business Media | isbn = 978-1-891483-62-2 | url = http://www.cancernetwork.com/cancer-management-11 | archive-url = https://web.archive.org/web/20090515031918/http://www.cancernetwork.com/cancer-management-11 | archive-date = 15 May 2009 | id = {{google books |id=wbLnPAAACAAJ}} }} * {{cite book | vauthors = Schwab M |title=Encyclopedia of Cancer |url={{google books |plainurl=y |id=mLUEf1kbbDgC}}|year= 2008|publisher=Springer Science & Business Media|isbn=978-3-540-36847-2}} * {{cite book | vauthors = Tannock I |title=The basic science of oncology |url={{google books |plainurl=y |id=Bb4F4pj2BdYC}}|year=2005|publisher=McGraw-Hill Professional|isbn=978-0-07-138774-3}} {{refend}} == External links == {{sisterlinks|d=Q12078|c=Category:Cancer (illness)|n=Category:Cancer|q=Cancer|b=no|v=Cell biology/Cancer|voy=no|m=no|mw=no|s=no|wikt=no|species=no}} {{EB1911 poster|Cancer}} * [https://www.iarc.who.int/cards_page/iarc-publications/ IARC Publications] (WHO) | [https://publications.iarc.fr/ Publications.iarc.fr] * [https://www.theatlantic.com/health/archive/2021/08/caitlin-flanagan-secret-of-surviving-cancer/619844/ "On telling cancer patients to have a positive attitude"] at ''[[The Atlantic]]'' * [https://www.who.int/news-room/fact-sheets/detail/cancer WHO fact sheet on cancer] * National Firefighter Registry (NFR) for Cancer, [[National Institute for Occupational Safety and Health|National Institute for Occupational Safety and Health (NIOSH)]], USA * [https://stopcarcinogensatwork.eu Stop carcinogens at work], EU OSHA. The site shares information to help prevent workers from being exposed to carcinogens in the workplace. * [https://www.cdc.gov/niosh/cancer/about/index.html Occupational Cancer], NIOSH. * NIOSH Pocket guide to chemical hazards, [https://www.cdc.gov/niosh/npg/nengapdxa.html#:~:text=Potential%20occupational%20carcinogen%20means%20any,more%20experimental%20mammalian%20species%20as Appendix A- NIOSH Potential Occupational Carcinogens]. {{Medical condition classification and resources | DiseasesDB = 28843 | ICD10 ={{ICD10|C00-C97}} | ICD9 = {{ICD9|140}}—{{ICD9|239}} | ICDO = | MedlinePlus = 001289 | eMedicineSubj = | eMedicineTopic = | MeshID = D009369 }} {{Tumors|state=uncollapsed}} {{Disease groups}} {{Authority control}} [[Category:Cancer]] [[Category:Aging-associated diseases]] [[Category:Oncology|*Cancer]] [[Category:Causes of amputation]] [[Category:Latin words and phrases]] [[Category:Wikipedia medicine articles ready to translate]] [[Category:Articles containing video clips]]
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