Cancer
Physical activity and risk of liver cancer in the NIH-AARP Diet and Health Study Frances Albers* Frances Albers Ghazaleh Dashti Charles Matthews Lin Yang Darren Brenner Roger Milne Dallas English Brigid Lynch Katherine McGlynn
Background: Physical activity reduces the risk of several cancers; however, evidence is less established for liver cancer, and the competing risk of death must be carefully considered. We estimated the effect of physical activity on risk of primary liver cancer using a formal causal inference framework for competing risks.
Methods: This analysis included data for 263,184 participants (870 liver cancers) in the NIH-AARP Diet and Health Study. The total effect of physical activity on risk of primary liver cancer was defined by conceptualizing competing death as a mediator on the causal pathway with a deterministic relationship with the outcome, such that if competing death = 1, primary liver cancer = 0. Risk differences (RDs) for the total effect were estimated as the differences in standardized, cause-specific cumulative incidence functions of primary liver cancer under exposure (≥ 4 hours/week of recreational moderate- to vigorous-intensity physical activity [MVPA]) versus no exposure (< 4 hours/week of MVPA). 95% confidence intervals (CIs) were obtained via the delta method. A sensitivity analysis was conducted for hepatocellular carcinoma (HCC), the most common histological subtype of primary liver cancer.
Results: RDs for the total effect of physical activity on risk of primary liver cancer at the average age of diagnosis (67 years) and average life expectancy (78 years) in the United States were estimated to be -18.1 (95% CI: -29.9, -6.2) and -58.4 (95% CI: -95.8, -21.1) cases per 100,000 persons, respectively. The magnitude of the RD increased from age 55 (RD per 100,000 persons = -2.0, 95% CI: -4.5, 0.6) to 85 years (RD per 100,000 persons = -79.0, 95% CI: -133.4, -24.7). Results for HCC were attenuated.
Conclusion: Physical activity may have a protective effect on primary liver cancer that increases with age.