An Integrative Approach for Deciphering the Causal Associations of Physical Activity and Cancer Risk: The Role of Adiposity

Abstract

Higher physical activity levels have been associated with about 10% to 25% reductions in up to 13 cancers. In isolation, these results are suggestive but not compelling enough to conclude causal associations, except for colon and breast cancer. However, knowledge on the relationships between obesity and cancer, between physical activity and overall and visceral adiposity, and between physical activity and obesity-related mediators of cancer risk can inform the epidemiology of physical activity and cancer. Excluding primarily smoking-related malignancies, for which residual confounding by smoking may occur, all 13 cancers associated with lower physical activity are also obesity-related. Moreover, the magnitude of the inverse association between physical activity and cancer type correlates highly with the association with body mass index (BMI) and cancer type (Spearman r = .79, two-sided P = .004). Physical activity lowers essentially all the obesity-related mediators of cancer, probably mediated largely through reductions in visceral adiposity. These findings strongly suggest that physical activity and adiposity are largely operating through similar carcinogenic mechanisms. That BMI has more robust associations than physical activity with cancer largely reflects that most populations studied have had great variation in BMI and little in physical activity. In populations with higher levels of physical activity and a lower range of BMI, physical activity may appear relatively more important. It may be useful to emphasize to clinicians and the public that physical activity, by acting on the same mechanisms, is likely to reduce risk of obesity-related cancers, even if the impact on lowering BMI is minimal.

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