We used the Swedish Cancer Registry data to address familial risks for concordant (same) and discordant (different) hepatobiliary cancers, including their associations with any other cancers and with known risk factors. Risks were also assessed between spouses. The analysis covered Swedish families and their cancers between years 1958 and 2018. Adjusted familial risks were expressed as standardized incidence ratios (SIRs). Familial SIRs for concordant hepatocellular carcinoma (HCC) were 2.60, and for gallbladder cancer they were at the same level (2.76). Familial risk was also found for intrahepatic bile duct cancer and for female extrahepatic bile duct cancer. HCC was associated with lung and cervical cancers; extrahepatic bile duct and ampullary cancers were associated with colon and pancreatic cancers, suggesting Lynch syndrome. Among spouses, hepatobiliary cancer was associated with HCC, stomach, pancreatic, cervical and upper aerodigestive tract cancers. Among risk factors, family members diagnosed with alcohol-related disease showed association with HCC. The observed familial risks for hepatobiliary cancers were relatively high, and considering the poor prognosis of these cancers, prevention is of the utmost importance and should focus on moderation of alcohol consumption, vaccination/treatment of hepatitis viral infections and avoidance of overweight and other risk factors of type 2 diabetes.

Biomedical Center Faculty of Medicine and Biomedical Center in Pilsen Charles University Prague 30605 Pilsen Czech Republic

Cancer Gene Therapy Group Translational Immunology Research Program University of Helsinki 00290 Helsinki Finland

Center for Community Based Healthcare Research and Education Department of Functional Pathology School of Medicine Shimane University Shimane 693 8501 Japan

Center for Primary Health Care Research Lund University 205 02 Malmö Sweden

Comprehensive Cancer Center Helsinki University Hospital 00290 Helsinki Finland

Department of Family Medicine and Community Health Icahn School of Medicine at Mount Sinai New York NY 10029 USA

Department of Population Health Science and Policy Icahn School of Medicine at Mount Sinai New York NY 10029 USA

Department of Surgery School of Medicine in Pilsen University Hospital Charles University 30605 Pilsen Czech Republic

Division of Cancer Epidemiology German Cancer Research Center Im Neuenheimer Feld 580 D 69120 Heidelberg Germany

Division of Pediatric Neurooncology German Cancer Research Center D 69120 Heidelberg Germany

Faculty of Medicine and Biomedical Center in Pilsen Charles University Prague 30605 Pilsen Czech Republic

Hopp Children's Cancer Center D 69120 Heidelberg Germany

Zobrazit více v PubMed

Valle J.W., Kelley R.K., Nervi B., Oh D.Y., Zhu A.X. Biliary tract cancer. Lancet. 2021;397:428–444. doi: 10.1016/S0140-6736(21)00153-7. PubMed DOI

Villanueva A., Longo D.L. Hepatocellular Carcinoma. N. Engl. J. Med. 2019;380:1450–1462. doi: 10.1056/NEJMra1713263. PubMed DOI

Baumeister S.E., Leitzmann M.F., Linseisen J., Schlesinger S. Physical Activity and the Risk of Liver Cancer: A Systematic Review and Meta-Analysis of Prospective Studies and a Bias Analysis. J. Natl. Cancer Inst. 2019;111:1142–1151. doi: 10.1093/jnci/djz111. PubMed DOI PMC

Hemminki K., Li X. Familial liver and gall bladder cancer: A nationwide epidemiological study from Sweden. Gut. 2003;52:592–596. doi: 10.1136/gut.52.4.592. PubMed DOI PMC

Liu X., Hemminki K., Försti A., Sundquist K., Sundquist J., Ji J. Cancer risk in patients with type 2 diabetes mellitus and their relatives. Int. J. Cancer. 2015;137:903–910. doi: 10.1002/ijc.29440. PubMed DOI

Castro F.A., Liu X., Försti A., Ji J., Sundquist J., Sundquist K., Koshiol J., Hemminki K. Increased risk of hepatobiliary cancers after hospitalization for autoimmune disease. Clin. Gastroenterol. Hepatol. 2014;12:1038–1045.e1037. doi: 10.1016/j.cgh.2013.11.007. PubMed DOI

McGee E.E., Castro F.A., Engels E.A., Freedman N.D., Pfeiffer R.M., Nogueira L., Stolzenberg-Solomon R., McGlynn K.A., Hemminki K., Koshiol J. Associations between autoimmune conditions and hepatobiliary cancer risk among elderly US adults. Int. J. Cancer. 2019;144:707–717. doi: 10.1002/ijc.31835. PubMed DOI PMC

Sundquist K., Sundquist J., Ji J. Risk of hepatocellular carcinoma and cancers at other sites among patients diagnosed with chronic hepatitis B virus infection in Sweden. J. Med. Virol. 2014;86:18–22. doi: 10.1002/jmv.23754. PubMed DOI

Liu X., Chen Y., Wang Y., Dong X., Wang J., Tang J., Sundquist K., Sundquist J., Ji J. Cancer risk in patients with hepatitis C virus infection: A population-based study in Sweden. Cancer Med. 2017;6:1135–1140. doi: 10.1002/cam4.988. PubMed DOI PMC

IARC Ionizing radiation, part 2: Some internally deposited radionuclides. Views and expert opinions of an IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Lyon, 14–21 June 2000. IARC Monogr. Eval. Carcinog. Risks Hum. 2001;78:1–559. PubMed PMC

Henriksson M., Björnsson B., Eilard M.S., Lindell G., Strömberg C., Hemmingsson O., Isaksson B., Rizell M., Sandström P. Treatment patterns and survival in patients with hepatocellular carcinoma in the Swedish national registry SweLiv. BJS Open. 2020;4:109–117. doi: 10.1002/bjs5.50226. PubMed DOI PMC

Arnold M., Pandeya N., Byrnes G., Renehan P.A.G., Stevens G.A., Ezzati P.M., Ferlay J., Miranda J.J., Romieu I., Dikshit R., et al. Global burden of cancer attributable to high body-mass index in 2012: A population-based study. Lancet Oncol. 2015;16:36–46. doi: 10.1016/S1470-2045(14)71123-4. PubMed DOI PMC

IARC Radiation. Volume 100 D. A review of human carcinogens. IARC Monogr. Eval. Carcinog. Risks Hum. 2012;100:1–341. PubMed

McGee E.E., Jackson S.S., Petrick J.L., Van Dyke A.L., Adami H.O., Albanes D., Andreotti G., Beane-Freeman L.E., de Gonzalez A.B., Buring J.E., et al. Smoking, Alcohol, and Biliary Tract Cancer Risk: A Pooling Project of 26 Prospective Studies. J. Natl. Cancer Inst. 2019;111:1263–1278. doi: 10.1093/jnci/djz103. PubMed DOI PMC

Frank C., Fallah M., Ji J., Sundquist J., Hemminki K. The population impact of familial cancer, a major cause of cancer. Int. J. Cancer. 2014;134:1899–1906. doi: 10.1002/ijc.28510. PubMed DOI

Hemminki K., Hemminki O., Forsti A., Sundquist K., Sundquist J., Li X. Familial risks for gallstones in the population of Sweden. BMJ Open Gastroenterol. 2018;4:e000188. doi: 10.1136/bmjgast-2017-000188. PubMed DOI PMC

Turati F., Edefonti V., Talamini R., Ferraroni M., Malvezzi M., Bravi F., Franceschi S., Montella M., Polesel J., Zucchetto A., et al. Family history of liver cancer and hepatocellular carcinoma. Hepatology. 2012;55:1416–1425. doi: 10.1002/hep.24794. PubMed DOI

Yang Y., Wu Q.J., Xie L., Chow W.H., Rothman N., Li H.L., Gao Y.T., Zheng W., Shu X.O., Xiang Y.B. Prospective cohort studies of association between family history of liver cancer and risk of liver cancer. Int. J. Cancer. 2014;135:1605–1614. doi: 10.1002/ijc.28792. PubMed DOI PMC

Kamsa-ard S., Kamsa-ard S., Luvira V., Suwanrungruang K., Vatanasapt P., Wiangnon S. Risk Factors for Cholangiocarcinoma in Thailand: A Systematic Review and Meta-Analysis. Asian Pac. J. Cancer Prev. 2018;19:605–614. doi: 10.22034/apjcp.2018.19.3.605. PubMed DOI PMC

Rawla P., Sunkara T., Thandra K.C., Barsouk A. Epidemiology of gallbladder cancer. Clin. Exp. Hepatol. 2019;5:93–102. doi: 10.5114/ceh.2019.85166. PubMed DOI PMC

Hemminki K., Hemminki A., Försti A., Sundquist K., Li X. Genetics of gallbladder cancer. Lancet Oncol. 2017;18:e296. doi: 10.1016/S1470-2045(17)30324-8. PubMed DOI

Li X., Xu W., Kang W., Wong S.H., Wang M., Zhou Y., Fang X., Zhang X., Yang H., Wong C.H., et al. Genomic analysis of liver cancer unveils novel driver genes and distinct prognostic features. Theranostics. 2018;8:1740–1751. doi: 10.7150/thno.22010. PubMed DOI PMC

Mehrotra R., Tulsyan S., Hussain S., Mittal B., Saluja S.S., Singh S., Tanwar P., Khan A., Javle M., Hassan M.M., et al. Genetic landscape of gallbladder cancer: Global overview. Mutat. Res. Rev. Mutat. Res. 2018;778:61–71. doi: 10.1016/j.mrrev.2018.08.003. PubMed DOI

Dominguez-Valentin M., Sampson J.R., Seppälä T.T., Ten Broeke S.W., Plazzer J.P., Nakken S., Engel C., Aretz S., Jenkins M.A., Sunde L., et al. Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: Findings from the Prospective Lynch Syndrome Database. Genet. Med. Off. J. Am. Coll. Med. Genet. 2020;22:15–25. doi: 10.1038/s41436-019-0596-9. PubMed DOI PMC

Møller P., Seppälä T.T., Bernstein I., Holinski-Feder E., Sala P., Evans D.G., Lindblom A., Macrae F., Blanco I., Sijmons R.H., et al. Cancer risk and survival in path_MMR carriers by gene and gender up to 75 years of age: A report from the Prospective Lynch Syndrome Database. Gut. 2018;67:1306–1316. doi: 10.1136/gutjnl-2017-314057. PubMed DOI PMC

Li X., Wu Y., Suo P., Liu G., Li L., Zhang X., Chen S., Xu M., Song L. Identification of a novel germline frameshift mutation p.D300fs of PMS1 in a patient with hepatocellular carcinoma: A case report and literature review. Medicine. 2020;99:e19076. doi: 10.1097/MD.0000000000019076. PubMed DOI PMC

Golan T., Raitses-Gurevich M., Kelley R.K., Bocobo A.G., Borgida A., Shroff R.T., Holter S., Gallinger S., Ahn D.H., Aderka D., et al. Overall Survival and Clinical Characteristics of BRCA-Associated Cholangiocarcinoma: A Multicenter Retrospective Study. Oncologist. 2017;22:804–810. doi: 10.1634/theoncologist.2016-0415. PubMed DOI PMC

Hemminki K., Ji J., Brandt A., Mousavi S.M., Sundquist J. The Swedish Family-Cancer Database 2009: Prospects for histology-specific and immigrant studies. Int. J. Cancer. 2010;126:2259–2267. doi: 10.1002/ijc.24795. PubMed DOI

Ludvigsson J.F., Andersson E., Ekbom A., Feychting M., Kim J.L., Reuterwall C., Heurgren M., Olausson P.O. External review and validation of the Swedish national inpatient register. BMC Public Health. 2011;11:450. doi: 10.1186/1471-2458-11-450. PubMed DOI PMC

Li X., Hemminki K. Cancer risks in women who had children with different partners from the Swedish Family-Cancer Database. Eur. J. Cancer Prev. 2002;11:433–438. doi: 10.1097/00008469-200210000-00005. PubMed DOI

Li X., Hemminki K. Cancer risks in men who had children with different partners from the Swedish Family-Cancer Database. Eur. J. Cancer Prev. 2003;12:355–358. doi: 10.1097/00008469-200310000-00002. PubMed DOI

Zheng G., Sundquist K., Sundquist J., Chen T., Försti A., Hemminki A., Liska V., Hemminki K. Second Primary Cancers after Liver, Gallbladder and Bile Duct Cancers, and These Cancers as Second Primary Cancers. Clin. Epidemiol. 2021;13:683–691. doi: 10.2147/CLEP.S318737. PubMed DOI PMC

Hemminki K., Tretli S., Sundquist J., Johannesen T.B., Granstrom C. Familial risks in nervous-system tumours: A histology-specific analysis from Sweden and Norway. Lancet Oncol. 2009;10:481–488. doi: 10.1016/S1470-2045(09)70076-2. PubMed DOI

Xue Y., Balci S., Mericoz C.A., Taskin O.C., Jiang H., Pehlivanoglu B., Muraki T., Memis B., Saka B., Kim G.E., et al. Frequency and clinicopathologic associations of DNA mismatch repair protein deficiency in ampullary carcinoma: Routine testing is indicated. Cancer. 2020;126:4788–4799. doi: 10.1002/cncr.33135. PubMed DOI

Wong W., Lowery M.A., Berger M.F., Kemel Y., Taylor B., Zehir A., Srinivasan P., Bandlamudi C., Chou J., Capanu M., et al. Ampullary cancer: Evaluation of somatic and germline genetic alterations and association with clinical outcomes. Cancer. 2019;125:1441–1448. doi: 10.1002/cncr.31951. PubMed DOI PMC

Hemminki K., Sundquist K., Sundquist J., Försti A., Hemminki A., Li X. Familial Risks and Proportions Describing Population Landscape of Familial Cancer. Cancers. 2021;13:4385. doi: 10.3390/cancers13174385. PubMed DOI PMC

Population-Attributable Fractions of Personal Comorbidities for Liver, Gallbladder, and Bile Duct Cancers

Survival in gastric and esophageal cancers in the Nordic countries through a half century