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Physical activity and the risk of liver cancer: a systematic review and meta-analysis of prospective studies and a bias analysis.

BACKGROUND
Physical inactivity is an established risk factor for several cancers of the digestive system and female reproductive organs but the evidence for liver cancers is less conclusive. The aim of this study was to synthesize prospective observational studies on the association of physical activity and liver cancer risk by means of a systematic review and meta-analysis.


METHODS
We searched Medline, Embase and Scopus from inception to January 2019 for prospective studies investigating the association of physical activity and liver cancer risk. We calculated mean hazard ratios (HR) and 95% confidence intervals (CI) using a random-effects model. We quantified the extent to which an unmeasured confounder or an unaccounted selection variable could shift the mean HR to the null.


RESULTS
Fourteen prospective studies, including 2,738 liver cancers, were included in the systematic review and meta-analysis. The mean HR for high compared to low physical activity was 0.75 (95% CI = 0.63 to 0.89; 95% prediction interval = 0.52 to 1.07; I² = 64.2%). We estimated that 67.6% (95% CI = 56.6 to 78.5) of all true effect estimates would have a HR < 0.8. Bias analysis suggested than an unobserved confounder would have to be associated with a 1.99-fold increase in the risk of physical activity or liver cancer to explain away the observed mean HR. An unaccounted for selection variable would have to be related to exposure and endpoint with a relative risk of 1.58 to explain away the mean HR.


CONCLUSION
Physical activity is inversely related to the risk of liver cancer. Further studies with objectively measured physical activity and quasi-experimental designs addressing confounding are needed.