Biological sex differences may explain why men face higher cancer risk than women
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Key takeaways:
- Men demonstrated a decreased risk for thyroid cancer and gallbladder cancer compared with women.
- Men had higher incidence of bladder cancer, gastric cardia cancer, larynx cancer and esophageal adenocarcinoma.
- Sex bias remained for most cancers after investigators controlled for factors like alcohol use, smoking, physical activity, diet and common medical conditions.
Men appeared to have a higher risk for cancer than women at most shared anatomic sites, according to study results published in Cancer.
The findings underscore a role for sex-related biological factors in cancer incidence, investigators concluded.
Background and methods
“There are many cancers that both men and women may develop, specifically those that do not affect the reproductive tract. However, men have higher rates of these nonreproductive cancers than women, with only two nonreproductive cancer types that are more common in women — thyroid and gallbladder,” Sarah S. Jackson, PhD, research fellow and independent research scholar in the infections and immunoepidemiology branch at the NIH, told Healio. “Historically, we have thought this is because women are less likely to smoke or drink and are more likely to eat well and exercise compared with men. This study sought to examine the sex bias in cancer incidence after controlling for those lifestyle factors to see if this explained the male predominance in cancer.”
The prospective cohort analyses included data from 171,274 men and 122,826 women included in the NIH-AARP Diet and Health Study between 1995 and 2011.
Researchers used cancer-specific Cox regression models to estimate male-to-female HRs. They used the Peters-Belson method to quantify the degree to which risk factors explained the observed male–female risk disparity.
Estimates of crude and covariate-adjusted male-to-female risk ratios of cancer incidence and quantification of the degree to which covariates/risk factors explained the male-to-female disparity in cancer risk served as the primary analytic goals.
Key findings
The analysis included 3,499,901 person-years of follow-up, with mean follow-up of 11.5 person-years for men and 12.4 person-years for women.
Researchers identified 26,693 incident cancers, of which 17,951 occurred among men and 8,742 among women.
The most common cancer types among men included lung, colon, skin, bladder and kidney cancers. The most common among women included lung, colon, pancreas and kidney cancers.
Researchers noted the highest age-adjusted male-to-female incident rate ratios (IRRs) for esophageal adenocarcinoma (IRR = 12.19; 95% CI, 8.32–17.86) and gastric cardia cancer (IRR = 4.93; 95% CI, 3.59–6.77).
After researchers adjusted for demographic, lifestyle and dietary covariates, they found that men had a lower risk for thyroid cancer (HR = 0.55; 95% CI, 0.46-0.66) and gallbladder cancer (HR = 0.33; 95% CI, 0.18-0.58) than women.
Conversely, they found that men had higher incidence of other cancer types (adjusted HR range, 1.3-10.8), including bladder cancer (HR = 3.33; 95% CI, 95% 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 = 10.8; 95% CI, 7.33-15.9).
“After controlling for factors like smoking, alcohol use, diet, physical activity and common medical conditions, the sex bias remained for most cancers,” Jackson told Healio. “We then statistically quantified the contribution of these risk factors to the male predominance and found that the risk factors were responsible for only a small fraction of the difference between men and women. For instance, differences [between men and women] in smoking, diet, and conditions like diabetes ... explains only 20% of the male bias in bladder cancer — a cancer that men are more than threefold more likely to develop than women.”
Implications
The study findings suggest that the lifestyle factors examined do not explain the sex difference in cancer incidence. This could indicate underlying biological differences between males and females that result in different subspecialties to cancer, including sex hormones, genetics and immune response, Jackson said.
“The dataset we used consists largely of non-Hispanic white adults. We’d, therefore, like to see if the same sex bias is present in other ethnic groups and to explore the contribution of sex hormones and genetics on cancer incidence in future research,” she said.
This study and others have deepened the understanding of sex disparities in various cancers; however, despite these efforts, sex disparities remain, according to an accompanying editorial by Jingqin R. Luo, PhD, and Graham A. Colditz, MD, DrPH, both researchers at Washington University School of Medicine in St. Louis.
“Strategically including sex as a biologic variable should be enforced along the whole cancer continuum, from risk prediction and cancer primary prevention, cancer screening, and secondary prevention to cancer treatment and patient management,” Luo and Colditz wrote. “Examining and addressing sex disparities in cancer (and other diseases) is an ongoing quest. Bench-to-bedside translational studies, which effectively transform the existing research findings into clinical practice, is a scalable means within easy reach to achieve precision medicine and will mitigate (and may ultimately eradicate) sex disparities in cancer.”
References:
- Jackson SS, et al. Cancer. 2022;doi:10.1002/cncr.34390.
- Luo JR, et al. Cancer. 2022;doi:10.1002/cncr.34389.
For more information:
Sarah S. Jackson, PhD, can be reached at sarah.jackson@nih.gov.
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Jackson SS, et al. Cancer. 2022;doi:10.1002/cncr.34390.
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