Clinical Epidemiology (Aug 2021)

Second Primary Cancers After Liver, Gallbladder and Bile Duct Cancers, and These Cancers as Second Primary Cancers

  • Zheng G,
  • Sundquist K,
  • Sundquist J,
  • Chen T,
  • Försti A,
  • Hemminki A,
  • Liska V,
  • Hemminki K

Journal volume & issue
Vol. Volume 13
pp. 683 – 691

Abstract

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Guoqiao Zheng,1– 3 Kristina Sundquist,3– 5 Jan Sundquist,3– 5 Tianhui Chen,6 Asta Försti,1,4,7,8 Akseli Hemminki,9,10 Vaclav Liska,11,12 Kari Hemminki1,2,4,12 1Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, D-69120, Germany; 2Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, D-69120, Germany; 3Center for Primary Health Care Research, Lund University, Malmö, 205 02, Sweden; 4Department of Family Medicine and Community Health, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 5Center for Community-based Healthcare Research and Education (CoHRE), Department of Functional Pathology, School of Medicine, Shimane University, Matsue, Japan; 6Department of Cancer Prevention, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer, Chinese Academy of Sciences, Hangzhou, 310022, People’s Republic of China; 7Hopp Children’s Cancer Center (KiTZ), Heidelberg, Germany; 8Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany; 9Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland; 10Comprehensive Cancer Center, Helsinki University Hospital, Helsinki, Finland; 11Department of Surgery, University Hospital, School of Medicine in Pilsen, Pilsen, Czech Republic; 12Biomedical Center, Faculty of Medicine and Biomedical Center in Pilsen, Charles University in Prague, Pilsen, 30605, Czech RepublicCorrespondence: Kari HemminkiBiomedical Center, Faculty of Medicine and Biomedical Center in Pilsen, Charles University, Pilsen, 30605, Czech RepublicTel +496221421800Fax +496221422203Email [email protected]: Second primary cancers (SPCs) are important clinically as they may negatively influence patient survival and they may tell about therapeutic side effects and general causes of cancer. Population-based literature concerning SPCs after hepatobiliary cancers is limited and here we assess risks of SPCs after hepatocellular cancer (HCC), and cancers of the gallbladder, bile ducts and ampulla of Vater. In reverse order, we consider the risk of hepatobiliary cancers as SPCs after any cancer.Methods: We used standardized incidence ratios (SIRs) to estimate bidirectional relative risks of subsequent cancers associated with hepatobiliary cancers. Cancer diagnoses were obtained from the Swedish Cancer Registry from years 1990 through 2015.Results: We identified 9997 primary HCCs, 1365 gallbladder cancers and 4721 bile duct cancers. After HCC, risks of four SPCs were increased: gallbladder (SIR = 4.38; 95% confidence interval 1.87– 8.67), thyroid (4.13; 1.30– 9.70), kidney (2.92; 1.66– 4.47) and squamous cell skin (1.55; 1.02– 2.26) cancers. In reverse order, HCC as SPC, in addition to the above cancers, associations included upper aerodigestive tract, esophageal, small intestinal and bladder cancers and non-Hodgkin lymphoma. For gallbladder and bile duct cancers, associations were found with small intestinal and pancreatic cancers.Conclusion: The results suggested that HCC is associated with two types of SPC, one related to shared environmental risk factors, such as alcohol, exemplified by upper aerodigestive tract and esophageal cancer, and the other related to immune dysfunction, exemplified by squamous cell skin cancer. SPCs associated with gallbladder and bile duct cancers suggest predisposition to mutations in the mismatch repair gene MLH1.Keywords: cancer incidence, relative risk, second primary cancer, cancer etiology, hepatobiliary cancer

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