Can body size explain the excess cancer risk in men?

Abstract

e13593 Background: Men are at increased risk of a majority of malignancies affecting both sexes. Since tall stature is associated with elevated cancer risk and since men are taller than women, we decided to investigate to what extent body stature, as a proxy for stem cell number within tissue, can explain the excess cancer risk in men. Methods: We performed a population-based cohort study investigating the association between male sex and cancer, accounting for body height. The analyses included all Swedish men and women with an adult height registration in either the Swedish Passport Register, the Conscription Register, and/or the Medical Birth Register (n = 6,156,659). Height data was linked to the Swedish Cancer Register where we observed 285,778 non-sex-specific cancer cases, diagnosed in 1960-2012. We applied contemporary causal mediation analysis methodology to assess the relative effect of male sex on lifetime cancer risk mediated by body height. Results: A vast majority of the investigated cancer sites were significantly associated with male sex (33 of 39) and height (27 of 39). The proportion of the excess cancer risk in men explained by sex differences in body height ranged from 0.5% (laryngeal) to 100% (salivary glands, colon, melanoma, and AML). The effect of body height and the mediated effect through height on cancer risk was most consistent and pronounced in malignancies with weak, few, or no known risk factors. Conclusions: A large proportion of the excess cancer risk in men is explainable by height. There is no known, height-associated cancer risk factor strong enough to provide an alternative pathway. Our findings supports the notion that a substantial proportion of cancer cases arise stochastically rather than are caused by underlying hereditary and/or environmental factors.