Men tend to have a higher risk of cancer than women, and factors such as smoking, alcohol use, and diet do not appear to explain this disparity, according to a study published in Cancer.

Researchers compared sex differences for 21 cancer types and found that men had a higher incidence of most cancers studied. 

For the most part, this higher susceptibility could not be explained by carcinogenic exposures. The researchers theorized that it might be explained by interrelated biological differences between the sexes. 

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This study was designed to assess behaviors, anthropometrics, lifestyles, and medical history to try to explain the higher risk of cancers in men. The researchers analyzed data from the National Institutes of Health-AARP Diet and Health Study (1995-2011). 

The cohort included 171,274 male and 122,826 female participants. There were a total of 26,693 incident cancers — 17,951 in men and 8742 in women. 

Men had a lower age-adjusted incidence of thyroid cancer (incidence rate ratio [IRR], 0.59; 95% CI, 0.49-0.70) and gallbladder cancer (IRR, 0.65; 95% CI, 0.44-0.94) than women. The incidence of anal cancer was similar between the groups (IRR, 0.97; 95% CI, 0.70-1.34).

For all other cancer types studied, men had a higher incidence than women. The greatest differences were seen for esophageal adenocarcinoma (IRR, 12.19; 95% CI, 8.32-17.86), gastric cardia cancer (IRR, 4.93; 95% CI, 3.59-6.77), and laryngeal cancer (IRR, 3.99; 95% CI, 3.07-5.17).

These 3 cancers had the highest male-to-female hazard ratios (HRs) when the researchers adjusted for demographic, lifestyle, and dietary factors. The HR was 10.80 for esophageal adenocarcinoma (95% CI, 7.33-15.90), 3.53 for laryngeal cancer (95% CI, 2.46-5.06), and 3.49 for gastric cardia cancer (95% CI, 2.26-5.37).

Men still had a lower risk of thyroid cancer (HR, 0.55; 95% CI, 0.46-0.66) and gallbladder cancer (HR, 0.33; 95% CI, 0.18-0.58) in the adjusted analysis as well.

The researchers noted that risk factors did explain a proportion of the male excess for esophageal adenocarcinoma and cancers of the 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),” the researchers wrote. 

“Collectively, our results point to the potential role of sex-related biologic mechanisms, rather than differences in carcinogenic exposures, as the major determinants of male-female differences in the risk of cancer at most shared anatomic sites. It is hypothesized that the higher cancer susceptibility at shared anatomic sites in men arises from several interrelated biologic differences between sexes, including physiologic, immunologic, genetic, epigenetic, and genomic mechanisms.”

The researchers suggested that global evaluation of these mechanisms across cancer sites should be conducted to help characterize whether they contribute to the greater burden of cancer in men.

Disclosures: One study author declared an affiliation with Merck. Please see the original reference for details.


Jackson SS, Marks MA, Katki HA, et al. Sex disparities in the incidence of 21 cancer types: Quantification of the contribution of risk factors. Cancer. Published online August 8, 2022. doi:10.1002/cncr.34390