Gender-Related Differences in the Incidence and Mortality of Late-Onset Colorectal Cancer: Estimates Based on the PLCO Cohort Study

Abstract

Background: Gender differences in colorectal cancer (CRC) are more pronounced among older adults (age ≥55 years), and few studies have comprehensively investigated variations in this age group. It is important to investigate patterns of age- and gender-driven differences in CRC incidence and mortality among older adults. Methods: We evaluated gender differences in CRC incidence and mortality utilizing Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial (126,291 subjects). The effect of gender differences on older adults was further confirmed in the Surveillance, Epidemiology, and End Results (SEER) database for (442,104 CRC cases). Incidence rate ratio (IRR) and mortality rate ratio (MRR) were estimated using Poisson regression models. Findings: We found that the IRR (male: female) increased from 1.33 at 55-59 years (33% higher in males) to 1.63 at 70-74 years (63% higher in males), even after adjusting for confounders. A similar trend of male predominance in CRC incidence was also observed in SEER (IRR=1.38-1.47, P<0.05). In particular, we observed that compared with age-matched females, older males were more likely to be diagnosed with left-sided, early-stage, and well/moderately differentiated CRC. The gender differences in CRC incidence were significant in nonsmoking subjects, normal weight/overweight subjects and subjects without a family history of CRC. Compared with age-matched females, males aged 70-74 years had a greater risk of fatal CRC (MRR=1.79, P<0.05). Interpretation: Understanding gender differences in CRC incidence and mortality may offer novel preventive strategies. Further functional studies are required to reveal the mechanisms underlying gender differences in CRC incidence and mortality. Funding: This study was supported by the National Key R&D Program of China (2017YFC0908200), the National Natural Science Foundation of China (81822039, 81872697, 81773516), the Foundation of Six Talent Peaks Project of Jiangsu (YY-020), and the Priority Academic Program Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine). Declaration of Interest: The authors declare no competing interests. Ethical Approval: Both study protocols were authorized by the ethics committees of the data providers and our university.