Editing Carcinogen

{{Short description|Substance, radionuclide, or radiation directly involved in causing cancer}}
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| footer = Common carcinogens; clockwise from top left: [[tobacco smoking]], [[alcohol and cancer|alcohol]], [[asbestos]], [[ultraviolet]] radiation
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A '''carcinogen''' ({{IPAc-en|k|ɑːr|ˈ|s|ɪ|n|ə|dʒ|ən}}) is any agent that promotes the development of [[cancer]].<ref name=":1">{{Cite web |title=Carcinogen |url=https://www.genome.gov/genetics-glossary/Carcinogen |access-date=2024-04-16 |website=www.genome.gov |language=en}}</ref>   Carcinogens can include [[synthetic chemical]]s, naturally occurring substances, physical agents such as ionizing and non-ionizing [[radiation]], and [[Biological agent|biologic agents]] such as viruses and [[carcinogenic bacteria|bacteria]].<ref name=":2" />  Most carcinogens act by creating mutations in [[DNA]] that disrupt a cell's normal processes for regulating growth, leading to uncontrolled cellular proliferation.<ref name=":1" /> This occurs when the cell's [[DNA repair]] processes fail to identify DNA damage allowing the defect to be passed down to [[daughter cells]]. The damage accumulates over time. This is typically a multi-step process during which the regulatory mechanisms within the cell are gradually dismantled allowing for unchecked [[Cell division|cellular division]].<ref name=":2">{{Cite web |title=Carcinogenesis |url=https://hemonc.mhmedical.com/content.aspx?sectionid=253777560&bookid=3022 |access-date=2024-04-16 |website=McGraw Hill Medical |language=en}}</ref>

The specific mechanisms for carcinogenic activity is unique to each agent and cell type. Carcinogens can be broadly categorized, however,  as activation-dependent and activation-independent which relate to the agent's ability to engage directly with DNA.<ref name=":0">{{cite journal |vauthors=Barnes JL, Zubair M, John K, Poirier MC, Martin FL |date=October 2018 |title=Carcinogens and DNA damage |journal=Biochemical Society Transactions |volume=46 |issue=5 |pages=1213–1224 |doi=10.1042/bst20180519 |pmc=6195640 |pmid=30287511}}</ref> Activation-dependent agents are relatively inert in their original form, but are bioactivated in the body into [[metabolite]]s or intermediaries capable of damaging human DNA.<ref name=":4">{{Cite journal |url=https://portlandpress.com/biochemsoctrans/article/46/5/1213/67954/Carcinogens-and-DNA-damage |access-date=2024-04-17 |journal=Biochemical Society Transactions |doi=10.1042/bst20180519 |pmc=6195640 |pmid=30287511 |title=Carcinogens and DNA damage |date=2018 |last1=Barnes |first1=Jessica L. |last2=Zubair |first2=Maria |last3=John |first3=Kaarthik |last4=Poirier |first4=Miriam C. |last5=Martin |first5=Francis L. |volume=46 |issue=5 |pages=1213–1224 }}</ref> These are also known as "indirect-acting" carcinogens. Examples of activation-dependent carcinogens include [[polycyclic aromatic hydrocarbon]]s (PAHs), [[heterocyclic aromatic amine]]s, and [[mycotoxin]]s. Activation-independent carcinogens, or "direct-acting" carcinogens, are those that are capable of directly damaging DNA without any modification to their molecular structure. These agents typically include [[Electrophile|electrophilic]] groups that react readily with the net negative charge of DNA molecules.<ref name=":0" /> Examples of  activation-independent carcinogens include [[Ultraviolet|ultraviolet light]], [[ionizing radiation]] and [[alkylating agent]]s.<ref name=":4" />

The time from exposure to a carcinogen to the development of cancer is known as the [[latency period]]. For most solid tumors in humans the latency period is between 10 and 40 years depending on cancer type.<ref name=":3">{{Cite book |last1=Ladou |last2=Harrison |title=Current Diagnosis and Treatment Occupational and Environmental Medicine |publisher=McGraw Hill Lange |year=2014 |isbn=978-1-260-14343-0 |edition=6th |pages=389–418}}</ref> For blood cancers, the latency period may be as short as two.<ref name=":3" /> Due to prolonged latency periods identification of carcinogens can be challenging.

A number of organizations review and evaluate the cumulative scientific evidence regarding the potential carcinogenicity of specific substances. Foremost among these is the [[International Agency for Research on Cancer]] (IARC). IARC routinely publishes monographs in which specific substances are evaluated for their potential carcinogenicity to humans and subsequently categorized into one of four groupings: Group 1: Carcinogenic to humans, Group 2A: Probably carcinogenic to humans, Group 2B:  Possibly carcinogenic to humans and Group 3: Not classifiable as to its carcinogenicity to humans.<ref>{{Cite web |title=IARC Monographs on the Identification of Carcinogenic Hazards to Humans|url=https://monographs.iarc.who.int/ |access-date=2024-04-17 |website=monographs.iarc.who.int |language=en-US}}</ref> Other organizations that evaluate the carcinogenicity of substances include the [[National Toxicology Program]] of the [[US Public Health Service]], [[NIOSH]], the [[American Conference of Governmental Industrial Hygienists]] and others.<ref>{{Cite web |title=Determining if Something Is a Carcinogen |url=https://www.cancer.org/cancer/risk-prevention/understanding-cancer-risk/determining-if-something-is-a-carcinogen.html |access-date=2024-04-17 |website=www.cancer.org |language=en}}</ref>

There are numerous sources of exposures to carcinogens including [[ultraviolet radiation]] from the sun, [[radon gas]]<ref>{{Cite web |last=CDC |date=2023-12-21 |title=Radon in the Home |url=https://www.cdc.gov/radon/radon-facts.html |access-date=2024-04-17 |website=Centers for Disease Control and Prevention |language=en-us}}</ref> emitted in residential basements, environmental contaminants such as [[chlordecone]], cigarette smoke and ingestion of some types of foods such as alcohol and [[processed meat]]s.<ref>{{Cite web |last=Underferth |first=Danielle |title=Processed meat and cancer: What you need to know |url=https://www.mdanderson.org/publications/focused-on-health/eat-less-processed-meat.h11-1590624.html |access-date=2024-04-17 |website=MD Anderson Cancer Center |language=en}}</ref> Occupational exposures represent a major source of carcinogens with an estimated 666,000 annual fatalities worldwide attributable to work related cancers.<ref name=":5">{{Cite journal |last1=Loomis |first1=Dana |last2=Guha |first2=Neela |last3=Hall |first3=Amy L |last4=Straif |first4=Kurt |date=August 2018 |title=Identifying occupational carcinogens: an update from the IARC Monographs |journal=Occupational and Environmental Medicine |language=en |volume=75 |issue=8 |pages=593–603 |doi=10.1136/oemed-2017-104944 |issn=1351-0711 |pmc=6204931 |pmid=29769352}}</ref> According to [[National Institute for Occupational Safety and Health|NIOSH]], 3-6% of cancers worldwide are due to occupational exposures.<ref name=":3" /> Well established occupational carcinogens include [[vinyl chloride]] and [[hemangiosarcoma]] of the liver, [[benzene]] and [[leukemia]], [[aniline dyes]] and [[bladder cancer]], [[asbestos]] and [[mesothelioma]], [[polycyclic aromatic hydrocarbon]]s and [[Chimney sweeps' carcinoma|scrotal cancer]] among chimney sweeps to name a few.

== Radiation ==
{{Main|radiation-induced cancer}}

=== Ionizing Radiation ===
[[CERCLA]] identifies all [[radionuclide]]s as carcinogens, although the nature of the emitted [[Radioactive decay|radiation]] ([[alpha particle|alpha]], [[beta particle|beta]], [[gamma ray|gamma]], or [[Neutron radiation|neutron]] and the radioactive strength), its consequent capacity to cause [[ionization]] in tissues, and the magnitude of radiation exposure, determine the potential hazard. Carcinogenicity of radiation depends on the type of radiation, type of exposure, and penetration. For example, [[alpha particle|alpha radiation]] has low penetration and is not a hazard outside the body, but emitters are carcinogenic when inhaled or ingested.  For example, [[Thorotrast]], a (incidentally radioactive) [[suspension (chemistry)|suspension]] previously used as a [[Radiocontrast|contrast]] medium in [[x-ray]] diagnostics, is a potent human carcinogen known because of its retention within various [[organ (biology)|organs]] and persistent emission of alpha particles.  Low-level ionizing radiation may induce irreparable DNA damage (leading to replicational and transcriptional errors needed for neoplasia or may trigger viral interactions) leading to pre-mature aging and [[cancer]].<ref>{{cite conference | vauthors = Acharya PV | title = The effect of ionizing radiation on the formation of age-correlated oligo deoxyribo nucleo phospheryl peptides in mammalian cells. | conference = 10th International Congress of Gerontology | location = Jerusalem | date = January 1975 }}</ref><ref>{{cite conference | vauthors = Acharya PV | title = Implications of The Action of Low-Level Ionizing Radiation on the Inducement of Irreparable DNA Damage Leading to Mammalian Aging and Chemical Carcinogenesis. | conference = 10th International Congress of Biochemistry | location = Hamburg, Germany | date = July 1976 }}</ref><ref>{{cite conference | vauthors = Acharya PV | title = Irreparable DNA-Damage by Industrial Pollutants in Pre-mature Aging, Chemical Carcinogenesis, and Cardiac Hypertrophy: Experiments and Theory | conference = 1st International Meeting of Heads of Clinical Biochemistry Laboratories | location = Jerusalem, Israel | date = April 1977 }}</ref>

=== Non-ionizing radiation ===
Not all types of electromagnetic radiation are carcinogenic. Low-energy waves on the [[electromagnetic spectrum]] including [[radio wave]]s, [[microwave]]s, [[infrared radiation]] and [[visible light]] are thought not to be, because they have insufficient energy to break chemical bonds. Evidence for carcinogenic effects of non-ionizing radiation is generally [[Electromagnetic radiation and health|inconclusive]], though there are some documented cases of radar technicians with prolonged high exposure experiencing significantly higher cancer incidence.<ref>{{cite journal | vauthors = Richter E, Berman T, Ben-Michael E, Laster R, Westin JB | title = Cancer in radar technicians exposed to radiofrequency/microwave radiation: sentinel episodes | journal = International Journal of Occupational and Environmental Health | volume = 6 | issue = 3 | pages = 187–193 | year = 2000 | pmid = 10926722 | doi = 10.1179/oeh.2000.6.3.187 | s2cid = 25147479 }}</ref>

Higher-energy radiation, including [[ultraviolet radiation]] (present in [[sunlight]]) generally ''is'' carcinogenic, if received in sufficient doses.   For most people, ultraviolet radiations from sunlight is the most common cause of skin cancer.  In Australia, where people with pale skin are often exposed to strong sunlight, [[melanoma]] is the most common cancer diagnosed in people aged 15–44 years.<ref>{{cite web|url=http://www.cancer.org.au/cancersmartlifestyle/SunSmart/Skincancerfactsandfigures.htm|title=Skin Cancer Facts and Figures|access-date=2010-07-02|archive-date=2012-08-10|archive-url=https://web.archive.org/web/20120810071104/http://www.cancer.org.au/cancersmartlifestyle/SunSmart/Skincancerfactsandfigures.htm|url-status=dead}}</ref><ref>{{cite web| url = https://www.newscientist.com/article/dn13922-skintone-gene-could-predict-cancer-risk.html| title = Skin-tone gene could predict cancer risk}}</ref>

Substances or [[Food irradiation|foods]] irradiated with electrons or electromagnetic radiation (such as microwave, X-ray or gamma) are not carcinogenic.<ref>{{cite web |author1=Center for Food Safety and Applied Nutrition |author1-link=Center for Food Safety and Applied Nutrition |title=Food Irradiation: What You Need to Know |url=https://www.fda.gov/food/buy-store-serve-safe-food/food-irradiation-what-you-need-know |website=FDA |access-date=20 January 2021 |language=en |date=20 April 2020}}</ref> In contrast, non-electromagnetic [[neutron radiation]] produced inside nuclear reactors can produce secondary radiation through [[nuclear transmutation]].

== Common carcinogens associated with food ==
=== Alcohol ===
{{main|Alcohol and cancer}}
[[Alcohol (drug)|Alcohol]] is a carcinogen of the head and neck, esophagus, liver, colon and rectum, and breast. It has a synergistic effect with tobacco smoke in the development of head and neck cancers. In the United States approximately 6% of cancers and 4% of cancer deaths are attributable to alcohol use.<ref>{{Cite web |title=Alcohol Use and Cancer |url=https://www.cancer.org/cancer/risk-prevention/diet-physical-activity/alcohol-use-and-cancer.html |access-date=2024-04-17 |website=www.cancer.org |language=en}}</ref>

=== Processed meats ===
Chemicals used in processed and cured meat such as some brands of bacon, sausages and ham may produce carcinogens.<ref>{{cite news |url=https://www.bbc.co.uk/news/health-34615621 |title=Processed meats do cause cancer - WHO|date= 26 October 2015 |work=BBC }}</ref> For example, nitrites used as food preservatives in cured meat such as bacon have also been noted as being carcinogenic with demographic links, but not causation, to colon cancer.<ref>{{cite journal | vauthors = Scanlan RA | title = Formation and occurrence of nitrosamines in food | journal = Cancer Research | volume = 43 | issue = 5 Suppl | pages = 2435s–2440s | date = May 1983 | pmid = 6831466 }}</ref>

=== Meats cooked at high temperatures ===
{{See also|Cooking#Carcinogens|Raw foodism}}
Cooking food at high temperatures, for example [[grilling]] or [[barbecuing]] meats, may also lead to the formation of minute quantities of many potent carcinogens that are comparable to those found in cigarette smoke (i.e., [[benzo(a)pyrene|benzo[''a'']pyrene]]).<ref name="pmid9827527">{{cite journal | vauthors = Zheng W, Gustafson DR, Sinha R, Cerhan JR, Moore D, Hong CP, Anderson KE, Kushi LH, Sellers TA, Folsom AR | title = Well-done meat intake and the risk of breast cancer | journal = Journal of the National Cancer Institute | volume = 90 | issue = 22 | pages = 1724–1729 | date = November 1998 | pmid = 9827527 | doi = 10.1093/jnci/90.22.1724 | doi-access = free }}</ref> [[Charring]] of food looks like [[coking]] and tobacco [[pyrolysis]], and produces carcinogens. There are several carcinogenic pyrolysis products, such as polynuclear aromatic hydrocarbons, which are converted by human [[enzyme]]s into [[epoxide]]s, which attach permanently to DNA. Pre-cooking meats in a [[microwave oven]] for 2–3 minutes before grilling shortens the time on the hot pan, and removes heterocyclic amine (HCA) precursors, which can help minimize the formation of these carcinogens.<ref>{{cite web|url=http://www.cancer.gov/cancertopics/factsheet/Risk/heterocyclic-amines |title=National Cancer Institute, 2004 analysis and recommendations |publisher=Cancer.gov |date=2004-09-15 |access-date=2010-09-22}}</ref>

=== Acrylamide in foods ===
Frying, grilling or broiling food at high temperatures, especially starchy foods, until a toasted crust is formed generates [[acrylamide]]s. This discovery in 2002 led to international health concerns. Subsequent research has however found that it is not likely that the acrylamides in burnt or well-cooked food cause cancer in humans; [[Cancer Research UK]] categorizes the idea that burnt food causes cancer as a "myth".<ref name="cruk">{{cite web |url=https://www.cancerresearchuk.org/about-cancer/causes-of-cancer/cancer-myths/can-eating-burnt-foods-cause-cancer |publisher=Cancer Research UK |title=Can eating burnt foods cause cancer? |date=15 October 2021 }}</ref>

== Biologic Agents ==
Several biologic agents are known carcinogens.

[[Aflatoxin]] B<sub>1</sub>, a toxin produced by the [[fungus]] ''[[Aspergillus flavus]]'' which is a common contaminant of stored [[cereal|grains]] and [[nut (fruit)|nuts]] is a known cause of [[Hepatocellular carcinoma|hepatocellular cancer]]. The bacteria [[Helicobacter pylori|H. Pylori]] is known to cause stomach cancer and [[MALT lymphoma]].<ref>{{Cite web |last=cancer |first=Canadian Cancer Society / Société canadienne du |title=Helicobacter pylori |url=https://cancer.ca/en/cancer-information/reduce-your-risk/get-vaccinated/helicobacter-pylori |access-date=2024-04-17 |website=Canadian Cancer Society |language=en}}</ref> [[Hepatitis B]] and C are associated with the development of hepatocellular cancer. [[Human papillomavirus infection|HPV]] is the primary cause of [[cervical cancer]].

== Cigarette smoke ==
{{Main|Health effects of tobacco}}

Tobacco smoke contains at least 70 known carcinogens and is implicated in the development of numerous types of cancers including cancers of the lung, larynx, esophagus, stomach, kidney, pancreas, liver, bladder, cervix, colon, rectum and blood.<ref>{{Cite web |last=CDC |date=2019-08-27 |title=Cancer and Tobacco Use |url=https://www.cdc.gov/vitalsigns/cancerandtobacco/index.html |access-date=2024-04-17 |website=Centers for Disease Control and Prevention |language=en-us}}</ref> Potent carcinogens found in cigarette smoke include [[polycyclic aromatic hydrocarbon]]s (PAH, such as benzo(a)pyrene), [[benzene]], and [[nitrosamine]].<ref>{{cite web |title=Harms of Cigarette Smoking and Health Benefits of Quitting |url=http://www.cancer.gov/about-cancer/causes-prevention/risk/tobacco/cessation-fact-sheet |work=National Cancer Institute |date=2017-12-21}}</ref><ref>{{cite web |url = http://oehha.ca.gov/prop65/hazard_ident/pdf_zip/FinalMJsmokeHID.pdf | vauthors = Tomar RC, Beaumont J, Hsieh JC 
|date = August 2009 |title = Evidence on the carcinogenicity of marijuana smoke |publisher = Reproductive and Cancer Hazard Assessment Branch Office of Environmental Health Hazard Assessment, California Environmental Protection Agency 
|access-date = 23 June 2012 }}</ref>

== Occupational carcinogens ==
Given that populations of workers are more likely to have consistent, often high level exposures to chemicals rarely encountered in normal life, much of the evidence for the carcinogenicity of specific agents is derived from studies of workers.<ref name=":5" />

<u>Selected carcinogens</u>

{| class="wikitable"
|-
! Carcinogen !! Associated cancer sites or types !! Occupational uses or sources
|-
! [[Arsenic]] and its compounds
|
* [[Lung]]
* [[Skin]]
* [[Hemangiosarcoma]]
|
* [[Smelting]] byproduct
* Component of:
**Alloys
**Electrical and [[semiconductor]] devices
**Medications (e.g. [[melarsoprol]])
**Herbicides
**Fungicides
**Animal dips
**Drinking water from contaminated aquifers.
|-
! [[Asbestos]]
|
* [[Lung cancer|Lungs]]
* [[Asbestosis]]
* [[Gastrointestinal cancer|Gastrointestinal tract]]
* [[Pleural]] mesothelioma
* [[Peritoneal mesothelioma]]
|
Not in widespread use, but found in:
* Constructions
**Roofing papers
**Floor tiles
* Fire-resistant textiles
* Friction linings (brake pads) (only outside Europe)
** Replacement friction linings for automobiles still may contain asbestos
|-
! [[Benzene]]
|
* [[Leukemia]]
* [[Hodgkin's lymphoma]]
|
* Light [[fuel oil]]
* Former use as [[solvent]]
* [[commodity chemical]]
|-
! [[Beryllium]] and its compounds<ref>{{cite journal |vauthors=Beyersmann D, Hartwig A |date=August 2008 |title=Carcinogenic metal compounds: recent insight into molecular and cellular mechanisms |journal=Archives of Toxicology |volume=82 |issue=8 |pages=493–512 |doi=10.1007/s00204-008-0313-y |pmid=18496671 |bibcode=2008ArTox..82..493B |s2cid=25513051}}</ref>
|
* Lung
|
* Lightweight alloys
**Aerospace applications
**Nuclear reactors
|-
! [[Cadmium]] and its compounds<ref>{{cite book |title=Cadmium: From Toxicity to Essentiality |vauthors=Hartwig A |publisher=Springer |year=2013 |isbn=978-94-007-5178-1 |veditors=Sigel A, Sigel H, Sigel RK |series=Metal Ions in Life Sciences |volume=11 |pages=491–507 |chapter=Cadmium and Cancer |doi=10.1007/978-94-007-5179-8_15 |pmid=23430782}}</ref>
|
* [[Prostate cancer|Prostate]]
|
* Yellow pigments
* [[Phosphor]]s
* [[Solder]]s
* Batteries
* Metal paintings and coatings
|-
! Hexavalent [[chromium]](VI) compounds
|
* Lung
|
* Paints
* Pigments
* Preservatives
|-
! [[Nitrosamine]]s<ref name="Tricker">{{cite journal |vauthors=Tricker AR, Preussmann R |year=1991 |title=Carcinogenic N-nitrosamines in the diet: occurrence, formation, mechanisms and carcinogenic potential |journal=Mutation Research |volume=259 |issue=3–4 |pages=277–289 |doi=10.1016/0165-1218(91)90123-4 |pmid=2017213}}</ref>
|
* Lung
* Esophagus
* Liver
|
* [[cigarette smoke]] 
*[[nitrite]]-treated foods (cured meats)
|-
! [[Ethylene oxide]]
|
* Leukemia
|
* [[commodity chemical]]
* [[Sterilant]] for hospital equipment
|-
! [[Nickel]]
|
* [[Nose]]
* Lung
|
* Nickel plating
* Ferrous alloys
* Ceramics
* Batteries
* Stainless-steel welding byproduct
|-
! [[Radon]] and its decay products
|
* Lung
|
* Uranium decay
**Quarries and mines
**Cellars and poorly ventilated places
|-
! [[Vinyl chloride]]
|
* Hemangiosarcoma
* [[liver cancer|Liver]]
|
* Production of [[polyvinyl chloride]]
|-
! Shift work that involves
[[circadian]] disruption<ref name="IARC180">{{Cite web |title=IARC Monographs Programme finds cancer hazards associated with shiftwork, painting and firefighting, International Agency for Research on Cancer |url=http://www.iarc.fr/en/media-centre/pr/2007/pr180.html |url-status=dead |archive-url=https://web.archive.org/web/20110721001355/http://www.iarc.fr/en/media-centre/pr/2007/pr180.html |archive-date=2011-07-21 |access-date=2011-07-01}}</ref>
|
* [[breast cancer|Breast]]
|
|-
! Involuntary smoking ([[Passive smoking]])<ref>{{cite book |url=http://monographs.iarc.fr/ENG/Monographs/vol83/ |title=Tobacco Smoke and Involuntary Smoking |date=2004 |publisher=International Agency for Research on Cancer (IARC), World Health Organization |series=IARC Monographs on the Evaluation of Carcinogenic Risks to Humans |volume=83 |archive-url=https://web.archive.org/web/20150315135351/http://monographs.iarc.fr/ENG/Monographs/vol83/ |archive-date=2015-03-15}}</ref>
|
* Lung
|
|-

! [[Radium-226]], [[Radium-224]],<br /> [[Plutonium-238]], [[Plutonium-239]]<ref name="Durbin75">{{cite conference|title=Survival, causes of death, and estimated tissue doses in a group of human beings injected with plutonium |url=http://www.osti.gov/energycitations/servlets/purl/4136654-rOiaqY/4136654.pdf |first1=R. E. |last1=Rowland |first2=Patricia W. |last2=Durbin |year=1975 |conference=Workshop on the biological effects and toxicity of Pu 239 and Ra 226}}</ref><br /> and other [[alpha particle]]<br /> emitters with high atomic weight
|
* [[Bone cancer|Bone]] (they are [[bone seeker]]s)
* [[Liver cancer|Liver]]
|
* [[Nuclear fuel]] processing
* [[Radium dial]] manufacturing
|-

| col span="3" | <small>Unless otherwise specified, ref is:<ref name="Kumar6-2">{{cite book |title=Robbins Basic Pathology |vauthors=Mitchell RS, Kumar V, Abbas AK, Fausto N |publisher=Saunders |year=2007 |isbn=978-1-4160-2973-1 |edition=8th |location=Philadelphia |quote=Table 6-2}}</ref></small>
|}

=== Others ===
* [[Gasoline]] (contains aromatics)
* [[Lead]] and its compounds
* [[Alkylating antineoplastic agent]]s (e.g., [[mechlorethamine]])
*[[Styrene]]
*Other [[alkylating agent]]s (e.g., [[dimethyl sulfate]])
* [[Ultraviolet radiation]] from the sun and UV lamps
* Other [[ionizing radiation]] (X-rays, gamma rays, etc.)
* Low refining or unrefined [[mineral oil]]s

== Mechanisms of carcinogenicity ==
Carcinogens can be classified as genotoxic or nongenotoxic. [[Genotoxin]]s cause irreversible genetic damage or mutations by binding to [[DNA]]. Genotoxins include chemical agents like [[N-nitroso-N-methylurea]] (NMU) or non-chemical agents such as [[ultraviolet light]] and [[ionizing radiation]]. Certain viruses can also act as carcinogens by interacting with DNA.

Nongenotoxins do not directly affect DNA but act in other ways to promote growth. These include hormones and some organic compounds.<ref>{{cite book| title=The Gale Encyclopedia of Cancer: A guide to Cancer and its Treatments |edition=Second |page=137 }}</ref>

== Classification ==
{| class="wikitable"  style="margin:0 0 0 0.5em; float:right;"
|+ Approximate equivalences<br />between classification schemes
|-
! IARC
! GHS
! NTP
! ACGIH
! EU
|-
| Group 1
| Cat. 1A
| style="text-align:center;"| Known
| style="text-align:center;"| A1
| Cat. 1A
|-
| Group 2A
| rowspan=2 | Cat. 1B
| rowspan="2" style="text-align:center;"| Reasonably<br />suspected
| rowspan="2" style="text-align:center;"| A2
| rowspan=2 | Cat. 1B
|-
| rowspan=2 | Group 2B
|-
| rowspan=2 | Cat. 2
| rowspan=4 | &nbsp;
| rowspan="2" style="text-align:center;"| A3
| rowspan=2 | Cat. 2
|-
| rowspan=2 | Group 3
|-
| rowspan=2 | &nbsp;
| style="text-align:center;"| A4
| rowspan=2 | &nbsp;
|-
| Group 4
| style="text-align:center;"| A5
|}

=== International Agency for Research on Cancer ===
The [[International Agency for Research on Cancer]] (IARC) is an intergovernmental agency established in 1965, which forms part of the [[World Health Organization]] of the [[United Nations]]. It is based in [[Lyon]], [[France]]. Since 1971 it has published a series of ''Monographs on the Evaluation                          of Carcinogenic Risks to Humans''<ref>{{cite web|url=http://monographs.iarc.fr/ |title=IARC Monographs |publisher=Monographs.iarc.fr |access-date=2010-09-22}}</ref> that have been highly influential in the classification of possible carcinogens.
* [[List of IARC Group 1 carcinogens|Group 1]]: the agent (mixture) is carcinogenic to humans. The exposure circumstance entails exposures that are carcinogenic to humans.
* [[List of IARC Group 2A carcinogens|Group 2A]]: the agent (mixture) is most likely (''product more likely to be'') carcinogenic to humans. The exposure circumstance entails exposures that are probably carcinogenic to humans.
* [[List of IARC Group 2B carcinogens|Group 2B]]: the agent (mixture) is possibly (''chance of product being'') carcinogenic to humans. The exposure circumstance entails exposures that are possibly carcinogenic to humans.
* [[List of IARC Group 3 carcinogens|Group 3]]: the agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans.
* [[List of IARC Group 4 carcinogens|Group 4]]: the agent (mixture) is most likely not carcinogenic to humans.

=== Globally Harmonized System ===
The [[Globally Harmonized System of Classification and Labelling of Chemicals]] (GHS) is a [[United Nations]] initiative to attempt to harmonize the different systems of assessing chemical risk which currently exist (as of March 2009) around the world. It classifies carcinogens into two categories, of which the first may be divided again into subcategories if so desired by the competent regulatory authority:
* Category 1: known or presumed to have carcinogenic potential for humans
** Category 1A: the assessment is based primarily on human evidence
** Category 1B: the assessment is based primarily on animal evidence
* Category 2: suspected human carcinogens

=== U.S. National Toxicology Program ===
The [[National Toxicology Program]] of the [[United States Department of Health and Human Services|U.S. Department of Health and Human Services]] is mandated to produce a biennial ''Report on Carcinogens''.<ref>Section 301(b)(4) of the Public Health Service Act, as amended by Section 262, Pub.&nbsp;L. 95–622.</ref> As of August 2024, the latest edition was the 15th report (2021).<ref name="roc">{{cite book | title = Report on Carcinogens | date = 2021 | edition = Fifteenth| publisher = U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program | url = https://ntp.niehs.nih.gov/whatwestudy/assessments/cancer/roc | archive-url=http://web.archive.org/web/20240812000000/https://ntp.niehs.nih.gov/whatwestudy/assessments/cancer/roc | archive-date = 12 August 2024 }}</ref> It classifies carcinogens into two groups:
* Known to be a human carcinogen
* Reasonably anticipated to be a human carcinogen

=== American Conference of Governmental Industrial Hygienists ===
The [[American Conference of Governmental Industrial Hygienists]] (ACGIH) is a private organization best known for its publication of [[threshold limit value]]s (TLVs) for occupational exposure and monographs on workplace chemical hazards. It assesses carcinogenicity as part of a wider assessment of the occupational hazards of chemicals.
* Group A1: Confirmed human carcinogen
* Group A2: Suspected human carcinogen
* Group A3: Confirmed animal carcinogen with unknown relevance to humans
* Group A4: Not classifiable as a human carcinogen
* Group A5: Not suspected as a human carcinogen

=== European Union ===

The European Union classification of carcinogens is contained in the Regulation (EC) No 1272/2008. It consists of three categories:<ref>{{Cite web |url=https://echa.europa.eu/documents/10162/13562/cmr_report_en.pdf |title = CMR substances from Annex VI of the CLP Regulation | publisher = European Chemicals Agency | date = May 2012 |access-date=2020-11-03 |archive-date=2021-02-24 |archive-url=https://web.archive.org/web/20210224221346/https://echa.europa.eu/documents/10162/13562/cmr_report_en.pdf |url-status=dead }}</ref>

* Category 1A: Carcinogenic
* Category 1B: May cause cancer
* Category 2: Suspected of causing cancer

The former European Union classification of carcinogens was contained in the [[Dangerous Substances Directive (67/548/EEC)|Dangerous Substances Directive]] and the [[Dangerous Preparations Directive]]. It also consisted of three categories:
* Category 1: Substances known to be carcinogenic to humans.
* Category 2: Substances which should be regarded as if they are carcinogenic to humans.
* Category 3: Substances which cause concern for humans, owing to possible carcinogenic effects but in respect of which the available information is not adequate for making a satisfactory assessment.
This assessment scheme is being phased out in favor of the GHS scheme (see above), to which it is very close in category definitions.

=== Safe Work Australia ===
Under a previous name, the NOHSC, in 1999 [[Safe Work Australia]] published the Approved Criteria for Classifying Hazardous Substances [NOHSC:1008(1999)].<ref name="Safe Work Australia3">{{cite web | url = http://www.safeworkaustralia.gov.au/AboutSafeWorkAustralia/WhatWeDo/Publications/Documents/504/Approved_Criteria_classifying_Hazardous_Substances_NOHSC1008_1999_2nd_Edition.pdf | work = Safe Work Australia | archive-url = https://web.archive.org/web/20101201103328/http://safeworkaustralia.gov.au/AboutSafeWorkAustralia/WhatWeDo/Publications/Documents/504/Approved_Criteria_classifying_Hazardous_Substances_NOHSC1008_1999_2nd_Edition.pdf |archive-date=2010-12-01 |url-status=dead |date= April 1999 | publisher = National Occupational Health and Safety Commission (NOHSC) | title = Approved criteria for classifying hazardous substances NOHSC:1008 (1999) }}</ref>
Section 4.76 of this document outlines the criteria for classifying carcinogens as approved by the Australian government. This classification consists of three categories:
* Category 1: Substances known to be carcinogenic to humans.
* Category 2: Substances that should be regarded as if they were carcinogenic to humans.
* Category 3: Substances that have possible carcinogenic effects in humans but about which there is insufficient information to make an assessment.

==Major carcinogens implicated in the four most common cancers worldwide==
In this section, the carcinogens implicated as the main causative agents of the four most common cancers worldwide are briefly described. These four cancers are lung, breast, colon, and stomach cancers.  Together they account for about 41% of worldwide cancer incidence and 42% of cancer deaths (for more detailed information on the carcinogens implicated in these and other cancers, see references<ref>{{cite book | vauthors = Bernstein H, Payne CM, Bernstein C, Garewal H, Dvorak K | date = 2008 | chapter = Cancer and aging as consequences of un-repaired DNA damage. | title = New Research on DNA Damages | veditors = Kimura H, Suzuki A | publisher = [[Nova Science Publishers, Inc.]] | location = New York | pages = 1–47 | chapter-url = https://www.novapublishers.com/catalog/product_info.php?products_id=43247 | archive-url = https://web.archive.org/web/20141025091740/https://www.novapublishers.com/catalog/product_info.php?products_id=43247 | archive-date=2014-10-25 | isbn = 978-1-60456-581-2}}</ref>).

===Lung cancer===
[[Lung cancer]] (pulmonary carcinoma) is the most common cancer in the world, both in terms of cases (1.6 million cases; 12.7% of total cancer cases) and deaths (1.4 million deaths; 18.2% of total cancer deaths).<ref name=Ferlay>{{cite journal | vauthors = Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM | title = Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008 | journal = International Journal of Cancer | volume = 127 | issue = 12 | pages = 2893–2917 | date = December 2010 | pmid = 21351269 | doi = 10.1002/ijc.25516 | s2cid = 23583962 | doi-access = free }}</ref>  Lung cancer is largely caused by tobacco smoke. Risk estimates for lung cancer in the United States indicate that tobacco smoke is responsible for 90% of lung cancers. Other factors are implicated in lung cancer, and these factors can interact synergistically with [[smoking]] so that total attributable risk adds up to more than 100%. These factors include occupational exposure to carcinogens (about 9-15%), [[radon]] (10%) and outdoor air pollution (1-2%).<ref>{{cite journal | vauthors = Alberg AJ, Ford JG, Samet JM | title = Epidemiology of lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition) | journal = Chest | volume = 132 | issue = 3 Suppl | pages = 29S–55S | date = September 2007 | pmid = 17873159 | doi = 10.1378/chest.07-1347 }}</ref>

Tobacco smoke is a complex mixture of more than 5,300 identified chemicals. The most important carcinogens in tobacco smoke have been determined by a "Margin of Exposure" approach.<ref>{{cite journal | vauthors = Cunningham FH, Fiebelkorn S, Johnson M, Meredith C | title = A novel application of the Margin of Exposure approach: segregation of tobacco smoke toxicants | journal = Food and Chemical Toxicology | volume = 49 | issue = 11 | pages = 2921–2933 | date = November 2011 | pmid = 21802474 | doi = 10.1016/j.fct.2011.07.019 }}</ref> Using this approach, the most important tumorigenic compounds in tobacco smoke were, in order of importance, [[acrolein]], [[formaldehyde]], [[acrylonitrile]], 1,3-butadiene, cadmium, acetaldehyde, ethylene oxide, and isoprene. Most of these compounds cause DNA damage by forming DNA adducts or by inducing other alterations in DNA.{{Citation needed|date=December 2019|reason=removed citation to book from predatory publisher}}  DNA damages are subject to error-prone DNA repair or can cause replication errors. Such errors in repair or replication can result in mutations in tumor suppressor genes or oncogenes leading to cancer.

===Breast cancer===
[[Breast cancer]] is the second most common cancer [(1.4 million cases, 10.9%), but ranks 5th as cause of death (458,000, 6.1%)].<ref name=Ferlay />  Increased risk of breast cancer is associated with persistently elevated blood levels of [[estrogen]].<ref>{{cite journal | vauthors = Yager JD, Davidson NE | title = Estrogen carcinogenesis in breast cancer | journal = The New England Journal of Medicine | volume = 354 | issue = 3 | pages = 270–282 | date = January 2006 | pmid = 16421368 | doi = 10.1056/NEJMra050776 | s2cid = 5793142 }}</ref>  Estrogen appears to contribute to breast carcinogenesis by three processes; (1) the metabolism of estrogen to genotoxic, [[4-Hydroxyestrone|mutagenic carcinogens]], (2) the stimulation of tissue growth, and (3) the repression of phase II [[detoxification]] enzymes that metabolize [[Reactive oxygen species|ROS]] leading to increased oxidative DNA damage.<ref>{{cite journal | vauthors = Ansell PJ, Espinosa-Nicholas C, Curran EM, Judy BM, Philips BJ, Hannink M, Lubahn DB | title = In vitro and in vivo regulation of antioxidant response element-dependent gene expression by estrogens | journal = Endocrinology | volume = 145 | issue = 1 | pages = 311–317 | date = January 2004 | pmid = 14551226 | doi = 10.1210/en.2003-0817 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Belous AR, Hachey DL, Dawling S, Roodi N, Parl FF | title = Cytochrome P450 1B1-mediated estrogen metabolism results in estrogen-deoxyribonucleoside adduct formation | journal = Cancer Research | volume = 67 | issue = 2 | pages = 812–817 | date = January 2007 | pmid = 17234793 | doi = 10.1158/0008-5472.CAN-06-2133 | s2cid = 24602808 | doi-access =  }}</ref><ref>{{cite journal | vauthors = Bolton JL, Thatcher GR | title = Potential mechanisms of estrogen quinone carcinogenesis | language = EN | journal = Chemical Research in Toxicology | volume = 21 | issue = 1 | pages = 93–101 | date = January 2008 | pmid = 18052105 | pmc = 2556295 | doi = 10.1021/tx700191p }}</ref>

The major estrogen in humans, [[estradiol]], can be metabolized to quinone derivatives that form [[DNA adduct|adducts]] with DNA.<ref name=Yue>{{cite journal | vauthors = Yue W, Santen RJ, Wang JP, Li Y, Verderame MF, Bocchinfuso WP, Korach KS, Devanesan P, Todorovic R, Rogan EG, Cavalieri EL | title = Genotoxic metabolites of estradiol in breast: potential mechanism of estradiol induced carcinogenesis | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 86 | issue = 3–5 | pages = 477–486 | date = September 2003 | pmid = 14623547 | doi = 10.1016/s0960-0760(03)00377-7 | s2cid = 31885800 }}</ref>  These derivatives can cause depurination, the removal of bases from the phosphodiester backbone of DNA, followed by inaccurate repair or replication of the apurinic site leading to mutation and eventually cancer.  This genotoxic mechanism may interact in synergy with estrogen receptor-mediated, persistent cell proliferation to ultimately cause breast cancer.<ref name=Yue /> Genetic background, dietary practices and environmental factors also likely contribute to the incidence of DNA damage and breast cancer risk.

Consumption of [[Alcohol (drug)|alcohol]] has also been linked to an increased risk for breast cancer.<ref>{{cite journal | vauthors = McDonald JA, Goyal A, Terry MB | title = Alcohol Intake and Breast Cancer Risk: Weighing the Overall Evidence | journal = Current Breast Cancer Reports | volume = 5 | issue = 3 | pages = 208–221 | date = September 2013 | pmid = 24265860 | pmc = 3832299 | doi = 10.1007/s12609-013-0114-z }}</ref>

===Colon cancer===

[[Colorectal cancer]] is the third most common cancer [1.2 million cases (9.4%), 608,000 deaths (8.0%)].<ref name=Ferlay /> Tobacco smoke may be responsible for up to 20% of colorectal cancers in the United States.<ref>{{cite journal | vauthors = Giovannucci E, Martínez ME | title = Tobacco, colorectal cancer, and adenomas: a review of the evidence | journal = Journal of the National Cancer Institute | volume = 88 | issue = 23 | pages = 1717–1730 | date = December 1996 | pmid = 8944002 | doi = 10.1093/jnci/88.23.1717 | doi-access =  }}</ref>  In addition, substantial evidence implicates [[bile acid]]s as an important factor in colon cancer.  Twelve studies (summarized in Bernstein et al.<ref name=Bernstein2009>{{cite journal | vauthors = Bernstein H, Bernstein C, Payne CM, Dvorak K | title = Bile acids as endogenous etiologic agents in gastrointestinal cancer | journal = World Journal of Gastroenterology | volume = 15 | issue = 27 | pages = 3329–3340 | date = July 2009 | pmid = 19610133 | pmc = 2712893 | doi = 10.3748/wjg.15.3329 | doi-access = free }}</ref>) indicate that the bile acids deoxycholic acid (DCA) or lithocholic acid (LCA) induce production of DNA-damaging reactive oxygen species or reactive nitrogen species in human or animal colon cells.  Furthermore, 14 studies showed that DCA and LCA induce DNA damage in colon cells.  Also 27 studies reported that bile acids cause programmed cell death ([[apoptosis]]).

Increased apoptosis can result in selective survival of cells that are resistant to induction of apoptosis.<ref name=Bernstein2009 />  Colon cells with reduced ability to undergo apoptosis in response to DNA damage would tend to accumulate mutations, and such cells may give rise to colon cancer.<ref name=Bernstein2009 />  Epidemiologic studies have found that fecal bile acid concentrations are increased in populations with a high incidence of colon cancer.  Dietary increases in total fat or saturated fat result in elevated DCA and LCA in feces and elevated exposure of the colon epithelium to these bile acids.  When the bile acid DCA was added to the standard diet of wild-type mice invasive colon cancer was induced in 56% of the mice after 8 to 10 months.<ref>{{cite journal | vauthors = Bernstein C, Holubec H, Bhattacharyya AK, Nguyen H, Payne CM, Zaitlin B, Bernstein H | title = Carcinogenicity of deoxycholate, a secondary bile acid | journal = Archives of Toxicology | volume = 85 | issue = 8 | pages = 863–871 | date = August 2011 | pmid = 21267546 | pmc = 3149672 | doi = 10.1007/s00204-011-0648-7 | bibcode = 2011ArTox..85..863B }}</ref>  Overall, the available evidence indicates that DCA and LCA are centrally important DNA-damaging carcinogens in colon cancer.

===Stomach cancer===
[[Stomach cancer]] is the fourth most common cancer [990,000 cases (7.8%), 738,000 deaths (9.7%)].<ref name=Ferlay />  ''[[Helicobacter pylori]]'' infection is the main causative factor in stomach cancer.  Chronic [[gastritis]] (inflammation) caused by ''H. pylori'' is often long-standing if not treated.  Infection of gastric epithelial cells with ''H. pylori'' results in increased production of reactive oxygen species (ROS).<ref>{{cite journal | vauthors = Ding SZ, Minohara Y, Fan XJ, Wang J, Reyes VE, Patel J, Dirden-Kramer B, Boldogh I, Ernst PB, Crowe SE | title = Helicobacter pylori infection induces oxidative stress and programmed cell death in human gastric epithelial cells | journal = Infection and Immunity | volume = 75 | issue = 8 | pages = 4030–4039 | date = August 2007 | pmid = 17562777 | pmc = 1952011 | doi = 10.1128/IAI.00172-07 }}</ref><ref>{{cite journal | vauthors = Handa O, Naito Y, Yoshikawa T | title = Redox biology and gastric carcinogenesis: the role of Helicobacter pylori | journal = Redox Report | volume = 16 | issue = 1 | pages = 1–7 | year = 2011 | pmid = 21605492 | pmc = 6837368 | doi = 10.1179/174329211X12968219310756 | doi-access = free }}</ref>  ROS cause oxidative DNA damage including the major base alteration 8-hydroxydeoxyguanosine (8-OHdG).  8-OHdG resulting from ROS is increased in chronic gastritis.  The altered DNA base can cause errors during DNA replication that have mutagenic and carcinogenic potential.  Thus ''H. pylori''-induced ROS appear to be the major carcinogens in stomach cancer because they cause oxidative DNA damage leading to carcinogenic mutations.

Diet is also thought to be a contributing factor in stomach cancer: in Japan, where very salty pickled foods are popular, the incidence of stomach cancer is high.  Preserved meat such as bacon, sausages, and ham increases the risk, while a diet rich in fresh fruit, vegetables, peas, beans, grains, nuts, seeds, herbs, and spices will reduce the risk. The risk also increases with age.<ref>{{cite web |url=http://www.cancerresearchuk.org/about-cancer/type/stomach-cancer/about/stomach-cancer-risks-and-causes |title=Stomach cancer risks and causes |work=Cancer Research UK }}</ref>

== See also ==
{{Columns-list|colwidth=30em|
* [[History of cancer]]
* [[Mutagen]]
* [[Possible carcinogen]]
* [[Safe handling of carcinogens]]
* [[Teratology]]
}}

== References ==
{{Reflist|30em}}

== External links ==
{{Wiktionary|carcinogen}}
{{Commons category|Carcinogens}}
* {{cite web | url = https://www.cdc.gov/niosh/topics/cancer/npotocca.html | title = Occupational Cancer - Carcinogen List | publisher = CDC | work = NIOSH Workplace Safety & Health |date= May 2, 2012 |url-status=dead |archive-url= https://web.archive.org/web/20230530104021/https://www.cdc.gov/niosh/topics/cancer/npotocca.html |archive-date= May 30, 2023 }}
* {{cite web | title=IARC Monographs on the Identification of Carcinogenic Hazards to Humans | website=International Agency for Research on Cancer | url=https://monographs.iarc.who.int/}}
* {{cite web | title = Known and Probable Carcinogens | url = http://www.cancer.org/docroot/PED/content/PED_1_3x_Known_and_Probable_Carcinogens.asp?sitearea=PED | work = American Cancer Society |date=2006 | archive-url=https://web.archive.org/web/20080317051133/http://www.cancer.org/docroot/PED/content/PED_1_3x_Known_and_Probable_Carcinogens.asp?sitearea=PED | archive-date=2008-03-17 }}
* {{cite web | title = Recognized Carcinogens | url = http://www.scorecard.org/health-effects/chemicals.tcl?short_hazard_name=cancer&all_p=t |website=Scorecard | archive-url = https://web.archive.org/web/20071217104833/http://www.scorecard.org/health-effects/chemicals.tcl?short_hazard_name=cancer&all_p=t | archive-date=2007-12-17 }}
* {{cite web | url = http://ntp.niehs.nih.gov/index.cfm?objectid=03C9B512-ACF8-C1F3-ADBA53CAE848F635 | work = U.S. National Toxicology Program | title = Report on Carcinogens | access-date = 2018-08-08 | archive-date = 2005-10-28 | archive-url = https://web.archive.org/web/20051028174523/http://ntp.niehs.nih.gov/index.cfm?objectid=03C9B512-ACF8-C1F3-ADBA53CAE848F635 | url-status = dead |date=2005 }}

{{Carcinogen|state=uncollapsed}}
{{Tumors}}
{{Toxicology}}
{{Genotoxicity}}
{{HealthIssuesOfPlastics}}
{{Authority control}}

[[Category:Carcinogens| ]]
[[Category:Carcinogenesis| ;]]
[[Category:Radiation health effects]]
[[Category:Occupational safety and health]]