The overall risk of developing cancer is about the same for men and women (40.2% and 38.5%, respectively). However, when excluding sex-specific cancers (like ovarian and testicular cancers), cancer risk becomes significantly higher in men than women, a detail that scientists have recognized for years. In fact, when considering cancers that develop in anatomic sites shared by men and women, men have more than a two-fold greater risk of most cancers than women. While research attributes some of these differences to behavioral factors, like smoking and alcohol use, or personal characteristics, like height , the increased cancer risk in men remains poorly understood. Additionally, there is evidence of a more active immune response in women compared to men, which could account for some differences in cancer incidence.
A new study published in Cancer suggests that biological factors may be a major factor contributing to the sex disparities seen in cancer incidence. The authors came to this conclusion through a highly selective process of elimination.
The researchers conducted a prospective cohort analysis of over 170,000 males and over 120,000 females aged 50 – 71. Participants enrolled in the NIH-AARP Diet and Health Study between 1995 and 1996, at which time they completed a questionnaire on diet and lifestyle. Over the next ten years, participants also provided information on risk factors like physical activity, cancer screening, and family history. Investigators obtained outcome data, including cancer diagnoses and death, from cancer registries and other databases.
The study evaluated 21 different types of cancer. Based on an extensive review of relevant literature for each cancer site, the researchers considered different variables for each type of cancer. The investigators then used statistical analyses to estimate male-to-female hazard ratios, a measurement of how often an event occurs in males compared to females.
The analysis revealed over 26,000 cancer diagnoses (17,951 in men and 8,742 in women). As expected, most cancers showed a higher cancer burden in men than women. The most considerable differences in risk appeared in cancers of the esophagus (10.8 times higher), bladder (3.5 times higher), larynx (3.5 times higher), and gastric cardia (3.3 times higher). Two cancer sites, the thyroid and gallbladder, revealed higher incidence in women than men. The risk factors evaluated explained a proportion of the measured excess male diagnoses for many cancers. However, the risk factors didn’t account for more than half of the male excess for any cancer evaluated. Sex disparate risk factors had the most significant impact on lung cancer, in which 49.5% of the difference in risk was attributable to risk factors.
The authors demonstrate that sex-related risk factors account for some, but not all, of the male predominance of cancer that has been long acknowledged but poorly understood. The authors conclude that their analysis suggests biological factors could explain the remaining discrepancies in cancer incidence between the sexes. Understanding these potential biological mechanisms could provide valuable clues to improve diagnosis, treatment, and prevention strategies.