Editing Cholangiocarcinoma (section)

==Risk factors==
[[File:Clonorchis sinensis LifeCycle.png|thumb|upright=1.3|Life cycle of ''[[Clonorchis sinensis]]'', a [[liver fluke]] associated with cholangiocarcinoma]]

Although most people present without any known risk factors evident, a number of [[risk factor]]s for the development of cholangiocarcinoma have been described. In the Western world, the most common of these is [[primary sclerosing cholangitis]] (PSC), an [[inflammatory disease]] of the bile ducts which is closely associated with [[ulcerative colitis]] (UC).<ref>{{cite journal | vauthors = Chapman RW | title = Risk factors for biliary tract carcinogenesis | journal = Annals of Oncology | volume = 10 | issue = Suppl 4 | pages = 308–11 | year = 1999 | pmid = 10436847 | doi = 10.1023/A:1008313809752 }}</ref> Epidemiologic studies have suggested that the lifetime risk of developing cholangiocarcinoma for a person with PSC is on the order of 10–15%,<ref>Epidemiologic studies which have addressed the incidence of cholangiocarcinoma in people with primary sclerosing cholangitis include the following:
* {{cite journal | vauthors = Bergquist A, Ekbom A, Olsson R, Kornfeldt D, Lööf L, Danielsson A, Hultcrantz R, Lindgren S, Prytz H, Sandberg-Gertzén H, Almer S, Granath F, Broomé U | display-authors = 6 | title = Hepatic and extrahepatic malignancies in primary sclerosing cholangitis | journal = Journal of Hepatology | volume = 36 | issue = 3 | pages = 321–7 | date = March 2002 | pmid = 11867174 | doi = 10.1016/S0168-8278(01)00288-4 }}
* {{cite journal | vauthors = Bergquist A, Glaumann H, Persson B, Broomé U | title = Risk factors and clinical presentation of hepatobiliary carcinoma in patients with primary sclerosing cholangitis: a case-control study | journal = Hepatology | volume = 27 | issue = 2 | pages = 311–6 | date = February 1998 | pmid = 9462625 | doi = 10.1002/hep.510270201 | doi-access = free }}
* {{cite journal | vauthors = Burak K, Angulo P, Pasha TM, Egan K, Petz J, Lindor KD | title = Incidence and risk factors for cholangiocarcinoma in primary sclerosing cholangitis | journal = American Journal of Gastroenterology | volume = 99 | issue = 3 | pages = 523–6 | date = March 2004 | doi = 10.1111/j.1572-0241.2004.04067.x | pmid = 15056096 | s2cid = 8412954 }}</ref> although autopsy series have found rates as high as 30% in this population.<ref name="autopsy" />  For inflammatory bowel disease patients with altered [[DNA repair]] functions, the progression from PSC to cholangiocarcinoma may be a consequence of [[DNA damage (naturally occurring)|DNA damage]] resulting from biliary inflammation and [[bile acids]].<ref>{{Cite journal |doi=10.1186/s12885-019-5391-0 |pmc=6394015 |pmid=30819129|title=Molecular Pathogenesis of Cholangiocarcinoma |year=2019 |last1=Labib |first1=Peter L. |last2=Goodchild |first2=George |last3=Pereira |first3=Stephen P. |journal=BMC Cancer |volume=19 |issue=1 |page=185 |doi-access=free }}</ref>The [[gut microbiota]] and [[bile acid]] activity are intricately linked and likely play crucial roles in cholangiocarcinoma development.<ref>{{cite journal |vauthors=Wu N, Bayatpour S, Hylemon PB, Aseem SO, Brindley PJ, Zhou H |title=Gut Microbiome and Bile Acid Interactions: Mechanistic Implications for Cholangiocarcinoma Development, Immune Resistance, and Therapy |journal=Am J Pathol |volume=195 |issue=3 |pages=397–408 |date=March 2025 |pmid=39730075 |doi=10.1016/j.ajpath.2024.11.004 |url=}}</ref>

Certain [[parasitic disease|parasitic liver diseases]] may be risk factors as well. Colonization with the [[liver fluke]]s ''[[Opisthorchis viverrini]]'' (found in Thailand, Laos PDR, and Vietnam)<ref>{{cite journal | vauthors = Watanapa P, Watanapa WB | title = Liver fluke-associated cholangiocarcinoma | journal = British Journal of Surgery | volume = 89 | issue = 8 | pages = 962–70 | date = August 2002 | pmid = 12153620 | doi = 10.1046/j.1365-2168.2002.02143.x | s2cid = 5606131 | doi-access = free }}</ref><ref name="pmid17622191">{{cite journal | vauthors = Sripa B, Kaewkes S, Sithithaworn P, Mairiang E, Laha T, Smout M, Pairojkul C, Bhudhisawasdi V, Tesana S, Thinkamrop B, Bethony JM, Loukas A, Brindley PJ | display-authors = 6 | title = Liver fluke induces cholangiocarcinoma | journal = PLOS Medicine | volume = 4 | issue = 7 | pages = e201 | date = July 2007 | pmid = 17622191 | pmc = 1913093 | doi = 10.1371/journal.pmed.0040201 | doi-access = free }}</ref><ref name="pmid20624536">{{Cite book | vauthors = Sripa B, Kaewkes S, Intapan PM, Maleewong W, Brindley PJ | title = Food-borne trematodiases in Southeast Asia epidemiology, pathology, clinical manifestation and control | journal = Advances in Parasitology | volume = 72 | pages = 305–50 | year = 2010 | pmid = 20624536 | doi = 10.1016/S0065-308X(10)72011-X | isbn = 9780123815132 }}</ref> or ''[[Clonorchis sinensis]]'' (found in China, Taiwan, eastern Russia, Korea, and Vietnam)<ref>{{cite journal | vauthors = Rustagi T, Dasanu CA | title = Risk factors for gallbladder cancer and cholangiocarcinoma: similarities, differences and updates | journal = Journal of Gastrointestinal Cancer | volume = 43 | issue = 2 | pages = 137–47 | date = June 2012 | pmid = 21597894 | doi = 10.1007/s12029-011-9284-y | s2cid = 31590872 }}</ref><ref>{{cite journal | vauthors = Hong ST, Fang Y | title = Clonorchis sinensis and clonorchiasis, an update | journal = Parasitology International | volume = 61 | issue = 1 | pages = 17–24 | date = March 2012 | pmid = 21741496 | doi = 10.1016/j.parint.2011.06.007 }}</ref> has been associated with the development of cholangiocarcinoma. Control programs ([[Integrated Opisthorchiasis Control Program]]) aimed at discouraging the consumption of raw and undercooked food have been successful at reducing the incidence of cholangiocarcinoma in some countries.<ref>{{cite journal | vauthors = Sripa B, Tangkawattana S, Sangnikul T | title = The Lawa model: A sustainable, integrated opisthorchiasis control program using the EcoHealth approach in the Lawa Lake region of Thailand | journal = Parasitology International | volume = 66 | issue = 4 | pages = 346–354 | date = August 2017 | pmid = 27890720 | pmc = 5443708 | doi = 10.1016/j.parint.2016.11.013 }}</ref> People with chronic liver disease, whether in the form of viral hepatitis (e.g. [[hepatitis B]] or [[hepatitis C]]),<ref>{{cite journal | vauthors = Kobayashi M, Ikeda K, Saitoh S, Suzuki F, Tsubota A, Suzuki Y, Arase Y, Murashima N, Chayama K, Kumada H | display-authors = 6 | title = Incidence of primary cholangiocellular carcinoma of the liver in Japanese patients with hepatitis C virus-related cirrhosis | journal = Cancer | volume = 88 | issue = 11 | pages = 2471–7 | date = June 2000 | pmid = 10861422 | doi = 10.1002/1097-0142(20000601)88:11<2471::AID-CNCR7>3.0.CO;2-T | s2cid = 22206944 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Yamamoto S, Kubo S, Hai S, Uenishi T, Yamamoto T, Shuto T, Takemura S, Tanaka H, Yamazaki O, Hirohashi K, Tanaka T | display-authors = 6 | title = Hepatitis C virus infection as a likely etiology of intrahepatic cholangiocarcinoma | journal = Cancer Science | volume = 95 | issue = 7 | pages = 592–5 | date = July 2004 | pmid = 15245596 | doi = 10.1111/j.1349-7006.2004.tb02492.x | doi-access = free | pmc = 11158843 }}</ref><ref>{{cite journal | vauthors = Lu H, Ye MQ, Thung SN, Dash S, Gerber MA | title = Detection of hepatitis C virus RNA sequences in cholangiocarcinomas in Chinese and American patients | journal = Chinese Medical Journal | volume = 113 | issue = 12 | pages = 1138–41 | date = December 2000 | pmid = 11776153 }}</ref> [[alcoholic liver disease]], or [[cirrhosis]] of the liver due to other causes, are at significantly increased risk of cholangiocarcinoma.<ref name="riskfactors" /><ref>{{cite journal | vauthors = Sorensen HT, Friis S, Olsen JH, Thulstrup AM, Mellemkjaer L, Linet M, Trichopoulos D, Vilstrup H, Olsen J | display-authors = 6 | title = Risk of liver and other types of cancer in patients with cirrhosis: a nationwide cohort study in Denmark | journal = Hepatology | volume = 28 | issue = 4 | pages = 921–5 | date = October 1998 | pmid = 9755226 | doi = 10.1002/hep.510280404 | s2cid = 72842845 }}</ref> [[HIV/AIDS|HIV infection]] was also identified in one study as a potential risk factor for cholangiocarcinoma, although it was unclear whether [[HIV]] itself or other correlated and confounding factors (e.g. hepatitis C infection) were responsible for the association.<ref name="riskfactors" />

Infection with the bacteria ''[[Helicobacter bilis]]'' and ''[[Helicobacter hepaticus]]'' species can cause biliary cancer.<ref name="ChangParsonnet2010">{{cite journal | vauthors = Chang AH, Parsonnet J | author2-link = Julie Parsonnet | title = Role of bacteria in oncogenesis | journal = Clinical Microbiology Reviews | volume = 23 | issue = 4 | pages = 837–57 | date = October 2010 | pmid = 20930075 | pmc = 2952975 | doi = 10.1128/CMR.00012-10 | doi-access = free | title-link = doi }}</ref>

[[Congenital disorder|Congenital]] liver abnormalities, such as [[Caroli disease]] (a specific type of five recognized [[choledochal cysts]]), have been associated with an approximately 15% lifetime risk of developing cholangiocarcinoma.<ref>{{cite journal | vauthors = Lipsett PA, Pitt HA, Colombani PM, Boitnott JK, Cameron JL | title = Choledochal cyst disease. A changing pattern of presentation | journal = Annals of Surgery | volume = 220 | issue = 5 | pages = 644–52 | date = November 1994 | pmid = 7979612 | pmc = 1234452 | doi = 10.1097/00000658-199411000-00007 }}</ref><ref>{{cite journal | vauthors = Dayton MT, Longmire WP, Tompkins RK | title = Caroli's Disease: a premalignant condition? | journal = American Journal of Surgery | volume = 145 | issue = 1 | pages = 41–8 | date = January 1983 | pmid = 6295196 | doi = 10.1016/0002-9610(83)90164-2 }}</ref> The rare inherited disorders [[Lynch syndrome]] II and biliary papillomatosis have also been found to be associated with cholangiocarcinoma.<ref>{{cite journal | vauthors = Mecklin JP, Järvinen HJ, Virolainen M | title = The association between cholangiocarcinoma and hereditary nonpolyposis colorectal carcinoma | journal = Cancer | volume = 69 | issue = 5 | pages = 1112–4 | date = March 1992 | pmid = 1310886 | doi = 10.1002/cncr.2820690508 | s2cid = 23468163 }}</ref><ref>{{cite journal | vauthors = Lee SS, Kim MH, Lee SK, Jang SJ, Song MH, Kim KP, Kim HJ, Seo DW, Song DE, Yu E, Lee SG, Min YI | display-authors = 6 | title = Clinicopathologic review of 58 patients with biliary papillomatosis | journal = Cancer | volume = 100 | issue = 4 | pages = 783–93 | date = February 2004 | pmid = 14770435 | doi = 10.1002/cncr.20031 | doi-access = free }}</ref> The presence of gallstones ([[cholelithiasis]]) is not clearly associated with cholangiocarcinoma. Intrahepatic stones (called [[hepatolithiasis]]), which are rare in the West but common in parts of Asia, have been strongly associated with cholangiocarcinoma.<ref>{{cite journal | vauthors = Lee CC, Wu CY, Chen GH | title = What is the impact of coexistence of hepatolithiasis on cholangiocarcinoma? | journal = Journal of Gastroenterology and Hepatology | volume = 17 | issue = 9 | pages = 1015–20 | date = September 2002 | pmid = 12167124 | doi = 10.1046/j.1440-1746.2002.02779.x | s2cid = 25753564 }}</ref><ref>{{cite journal | vauthors = Su CH, Shyr YM, Lui WY, P'Eng FK | title = Hepatolithiasis associated with cholangiocarcinoma | journal = British Journal of Surgery | volume = 84 | issue = 7 | pages = 969–73 | date = July 1997 | pmid = 9240138 | doi = 10.1002/bjs.1800840717 | s2cid = 29475282 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Donato F, Gelatti U, Tagger A, Favret M, Ribero ML, Callea F, Martelli C, Savio A, Trevisi P, Nardi G | display-authors = 6 | title = Intrahepatic cholangiocarcinoma and hepatitis C and B virus infection, alcohol intake, and hepatolithiasis: a case-control study in Italy | journal = Cancer Causes & Control | volume = 12 | issue = 10 | pages = 959–64 | date = December 2001 | pmid = 11808716 | doi = 10.1023/A:1013747228572 | s2cid = 12117363 }}</ref> Exposure to [[Thorotrast]], a form of [[thorium dioxide]] which was used as a [[radiocontrast|radiologic contrast medium]], has been linked to the development of cholangiocarcinoma as late as 30–40 years after exposure; Thorotrast was banned in the United States in the 1950s due to its [[carcinogenicity]].<ref>{{cite journal | vauthors = Sahani D, Prasad SR, Tannabe KK, Hahn PF, Mueller PR, Saini S | title = Thorotrast-induced cholangiocarcinoma: case report | journal = Abdominal Imaging | volume = 28 | issue = 1 | pages = 72–4 | year = 2003 | pmid = 12483389 | doi = 10.1007/s00261-001-0148-y | s2cid = 23531547 }}</ref><ref>{{cite journal | vauthors = Zhu AX, Lauwers GY, Tanabe KK | title = Cholangiocarcinoma in association with Thorotrast exposure | journal = Journal of Hepato-Biliary-Pancreatic Surgery | volume = 11 | issue = 6 | pages = 430–3 | year = 2004 | pmid = 15619021 | doi = 10.1007/s00534-004-0924-5 }}</ref><ref>{{cite journal | vauthors = Lipshutz GS, Brennan TV, Warren RS | title = Thorotrast-induced liver neoplasia: a collective review | journal = Journal of the American College of Surgeons | volume = 195 | issue = 5 | pages = 713–8 | date = November 2002 | pmid = 12437262 | doi = 10.1016/S1072-7515(02)01287-5 }}</ref>