Height as a mediator of sex differences in cancer risk

Abstract

Globally, age-standardized incidence rates for most cancers at shared sites are substantially and consistently higher in men than in women. Differences in established risk factors are unable to account for much of the sex disparity. We hypothesized that variability in height may be important in explaining sex differences in cancer risk. We included 49372 men from the Health Professionals Follow-up Study (1986-2014) and 115612 women from the Nurses' Health Study (1980-2014). Height was reported at baseline and biennial questionnaires were used to collect information on cancer risk factors. We examined the association between sex and cancer incidence at shared anatomic sites using Cox proportional hazards models and performed mediation analysis to determine the percent of the association that was accounted for by height. Over up to 34 years of follow-up, 21307 incident cases of cancers at shared sites (7705 men, 13602 women) were documented. After adjusting for major cancer risk factors, men had a 39% increased risk of shared cancers overall (hazard ratio= 1.39; 95% confidence interval= 1.33-1.45) of which 35% (95% confidence interval= 24-46) was mediated by height. The excess risk of cancer for men was also partially explained by height for several specific cancers (gastrointestinal, melanoma, kidney, brain, hematologic). Mediation by height tended to be stronger among never smokers or those who adhered to a healthy lifestyle, and for cancers with fewer known environmental risk factors. Differences in height among men and women partially mediated the association between sex and cancer incidence at several shared sites. Hence, mechanisms underlying the relationship between height and cancer may be important determinants of sex disparities in cancer incidence.