Abstract
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). 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). 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. These findings suggest an inverse association between physical activity and risk of HCC, which is potentially mediated by obesity. 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.
Highlights
1 MethodsIn a subset [17] of the EPIC cohort as of 2006, sera samples for Hepatitis B virus (HBV) (ARCHITECT HBsAg, Abbott Diagnostics, France) and Hepatitis C virus (HCV) serologic tests were available: 115 hepatocellular carcinoma (HCC) cases were matched using incidence density sampling to 230 controls based on age at blood collection, sex, study center, time of the day at blood collection, fasting status at blood collection; among women, by menopausal status, and hormone replacement therapy use at time of blood collection
Waist circumference explained about 40% and body mass index 30% of the overall association of total physical activity and HCC. Conclusions: Findings suggest an inverse association between physical activity and risk of HCC, which is potentially mediated by obesity
Physical Activity and Hepatobiliary Cancer Risk Total physical activity and vigorous physical activity were inversely associated with HCC but not with intrahepatic bile duct cancers (IHBC) and NBGC
Summary
In a subset [17] of the EPIC cohort as of 2006, sera samples for HBV (ARCHITECT HBsAg, Abbott Diagnostics, France) and HCV (anti-HCV chemiluminescent microparticle immunoassays, Abbott Diagnostics, France) serologic tests were available: 115 HCC cases were matched using incidence density sampling to 230 controls based on age at blood collection, sex, study center, time of the day at blood collection, fasting status at blood collection; among women, by menopausal status, and hormone replacement therapy use at time of blood collection These data were used in nested case-control analyses to examine potential confounding by viral hepatitis status for the association of physical activity and HCC. Recreational physical activity was assessed by querying about the amount of time in hours per week during the winter and summer spent with cycling and other physical exercises (e.g., jogging, swimming) and was summarized into four groups: inactive, moderately inactive, moderately active, and active [21, 22] Participants reported their level of occupational physical activity as either sedentary, standing, manual work or heavy manual work. We examined this association in the European Prospective 4 Investigation into Cancer and Nutrition cohort (EPIC)
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