Association between physical activity and risk of hepatobiliary cancers: A multinational cohort study

Sebastian E. Baumeister, Sabrina Schlesinger, Krasimira Aleksandrova, Carmen Jochem, Mazda Jenab, Marc J. Gunter, Kim Overvad, Anne Tjønneland, Marie Christine Boutron-Ruault, Franck Carbonnel, Agnès Fournier, Tilman Kühn, Rudolf Kaaks, Tobias Pischon, Heiner Boeing, Antonia Trichopoulou, Christina Bamia, Carlo La Vecchia, Giovanna Masala, Salvatore PanicoFrancesca Fasanelli, Rosario Tumino, Sara Grioni, Bas Bueno de Mesquita, Roel Vermeulen, Anne M. May, Kristin B. Borch, Sunday O. Oyeyemi, Eva Ardanaz, Miguel Rodríguez-Barranco, María Dolores Chirlaque López, Mireia Felez-Nobrega, Emily Sonestedt, Bodil Ohlsson, Oskar Hemmingsson, Mårten Werner, Aurora Perez-Cornago, Pietro Ferrari, Magdalena Stepien, Heinz Freisling, Konstantinos K. Tsilidis, Heather Ward, Elio Riboli, Elisabete Weiderpass, Michael F. Leitzmann

Research output: Contribution to journalArticlepeer-review


Background & Aims: To date, evidence on the association between physical activity and risk of hepatobiliary cancers has been inconclusive. We examined this association in the European Prospective Investigation into Cancer and Nutrition cohort (EPIC). Methods: We identified 275 hepatocellular carcinoma (HCC) cases, 93 intrahepatic bile duct cancers (IHBCs), and 164 non-gallbladder extrahepatic bile duct cancers (NGBCs) among 467,336 EPIC participants (median follow-up 14.9 years). We estimated cause-specific hazard ratios (HRs) for total physical activity and vigorous physical activity and performed mediation analysis and secondary analyses to assess robustness to confounding (e.g. due to hepatitis virus infection). Results: In the EPIC cohort, the multivariable-adjusted HR of HCC was 0.55 (95% CI 0.38–0.80) comparing active and inactive individuals. Regarding vigorous physical activity, for those reporting >2 hours/week compared to those with no vigorous activity, the HR for HCC was 0.50 (95% CI 0.33–0.76). Estimates were similar in sensitivity analyses for confounding. Total and vigorous physical activity were unrelated to IHBC and NGBC. In mediation analysis, waist circumference explained about 40% and body mass index 30% of the overall association of total physical activity and HCC. Conclusions: These findings suggest an inverse association between physical activity and risk of HCC, which is potentially mediated by obesity. Lay summary: In a pan-European study of 467,336 men and women, we found that physical activity is associated with a reduced risk of developing liver cancers over the next decade. This risk was independent of other liver cancer risk factors, and did not vary by age, gender, smoking status, body weight, and alcohol consumption.

Original languageEnglish
Pages (from-to)885-892
Number of pages8
JournalJournal of Hepatology
Issue number5
Publication statusPublished - May 2019


  • Hepatobiliary cancer
  • Hepatocellular carcinoma
  • Liver cancer
  • Physical activity

ASJC Scopus subject areas

  • Hepatology


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