Sex disparities in the incidence of 21 cancer types: Quantification of the contribution of risk factors

Abstract

Background: Cancer incidence is higher in men than in women at most shared anatomic sites for currently unknown reasons. The authors quantified the extent to which behaviors (smoking and alcohol use), anthropometrics (body mass index and height), lifestyles (physical activity, diet, medications), and medical history collectively explain the male predominance of risk at 21 shared cancer sites.

Methods: Prospective cohort analyses (n = 171,274 male and n = 122,826 female participants; age range, 50-71 years) in the National Institutes of Health-AARP Diet and Health Study (1995-2011). Cancer-specific Cox regression models were used to estimate male-to-female hazard ratios (HRs). The degree to which risk factors explained the observed male-female risk disparity was quantified using the Peters-Belson method.

Results: There were 26,693 incident cancers (17,951 in men and 8742 in women). Incidence was significantly lower in men than in women only for thyroid and gallbladder cancers. At most other anatomic sites, the risks were higher in men than in women (adjusted HR range, 1.3-10.8), with the strongest increases for bladder cancer (HR, 3.33; 95% confidence interval [CI], 2.93-3.79), gastric cardia cancer (HR, 3.49; 95% CI, 2.26-5.37), larynx cancer (HR, 3.53; 95% CI, 2.46-5.06), and esophageal adenocarcinoma (HR, 10.80; 95% CI, 7.33-15.90). Risk factors explained a statistically significant (nonzero) proportion of the observed male excess for esophageal adenocarcinoma and cancers of liver, other biliary tract, bladder, skin, colon, rectum, and lung. However, only a modest proportion of the male excess was explained by risk factors (ranging from 50% for lung cancer to 11% for esophageal adenocarcinoma).

Conclusions: Men have a higher risk of cancer than women at most shared anatomic sites. Such male predominance is largely unexplained by risk factors, underscoring a role for sex-related biologic factors.

Keywords: cancer; health disparities; incidence; sex differences.

Figure 1.

Observed ten-year cancer incidence rates per 100,000 in males and females, with Peters-Belson estimates expressed as a percentage Abbreviations: AC, adenocarcinoma; H&N, head and neck; and SCC, squamous cell carcinoma. The observed survival curves for males (M_inc) and females (F_inc) were estimated (10-year incidence per 100,000) and a cancer site-specific Cox model in males was applied to females to predict their counterfactual survival if they had been males (C_inc). The Peters-Belson estimate for the male-to-female disparity in cancer risk that is explained by differences in multivariable covariate distributions between males and females was calculated as (M_inc – C_inc)/(M_inc – F_inc), expressed as a percentage. A positive Peters-Belson estimate indicates that the male-to-female difference in cancer risk is explained by differences in covariate/risk factor distributions between men and women, while a negative estimate indicates the male-to-female disparities would be greater if men had the same covariate distribution as women. Peters-Belson estimates are shown on the left; red font indicates the estimate is statistically significant.