Associations between autoimmune conditions and hepatobiliary cancer risk among elderly US adults

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Growing evidence suggests that people with autoimmune conditions may be at increased risk of hepatobiliary tumors. In the present study, we evaluated associations between autoimmune conditions and hepatobiliary cancers among adults aged ≥66 in the United States. We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data (1992–2013) to conduct a population-based, case–control study. Cases (n = 32,443) had primary hepatobiliary cancer. Controls (n = 200,000) were randomly selected, cancer-free adults frequency-matched to cases by sex, age and year of selection. Using multivariable logistic regression, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) for associations with 39 autoimmune conditions identified via Medicare claims. We also conducted separate analyses for diagnoses obtained via inpatient versus outpatient claims. Sixteen conditions were associated with at least one hepatobiliary cancer. The strongest risk estimates were for primary biliary cholangitis with hepatocellular carcinoma (OR: 31.33 [95% CI: 23.63–41.56]) and primary sclerosing cholangitis with intrahepatic cholangiocarcinoma (7.53 [5.73–10.57]), extrahepatic cholangiocarcinoma (5.59 [4.03–7.75]), gallbladder cancer (2.06 [1.27–3.33]) and ampulla of Vater cancer (6.29 [4.29–9.22]). Associations with hepatobiliary-related conditions as a group were observed across nearly all cancer sites (ORs ranging from 4.53 [95% CI: 3.30–6.21] for extrahepatic cholangiocarcinoma to 7.18 [5.94–8.67] for hepatocellular carcinoma). Restricting to autoimmune conditions diagnosed via inpatient claims, 6 conditions remained associated with at least one hepatobiliary cancer, and several risk estimates increased. In the outpatient restricted analysis, 12 conditions remained associated. Multiple autoimmune conditions are associated with hepatobiliary cancer risk in the US Medicare population, supporting a shared immuno-inflammatory etiology to these cancers.


  • Emma E. McGee
  • Felipe A. Castro
  • Eric A. Engels
  • Neal D. Freedman
  • Ruth M. Pfeiffer
  • Leticia Nogueira
  • Rachael Stolzenberg-Solomon
  • Katherine A. McGlynn
  • Kari Hemminki
  • Jill Koshiol
External organisations
  • National Cancer Institute, USA
  • American Cancer Society
  • German Cancer Research Centre
  • Roche Innovation Center
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology
  • Rheumatology and Autoimmunity


  • ampulla of Vater cancer, extrahepatic cholangiocarcinoma, gallbladder cancer, hepatocellular carcinoma, intrahepatic cholangiocarcinoma
Original languageEnglish
Pages (from-to)707-717
JournalInternational Journal of Cancer
Issue number4
Early online date2018 Aug 28
Publication statusPublished - 2019 Feb 15
Publication categoryResearch