Abstract / Summary
Importance: Cancer risk is higher in males than females globally. Whether this sex disparity reflects a biological inevitability or is potentially modifiable by lifestyle behaviors and health conditions across diverse populations remains unclear.
Objective: To determine the contribution of lifestyle factors and health conditions to sex disparities in cancer incidence across populations.
Design, setting, and participants: This cohort study conducted an individual-level analysis of 3 population-based prospective cohorts in China (Shanghai Men's Health Study and Shanghai Women's Health Study) and the UK (UK Biobank) of adults aged 40 to 74 years at baseline with no prior cancer. Baseline data were collected from 1997 to 2010, with follow-up through 2021. Data were analyzed from September 2025 to June 2026.
Exposures: Eleven risk factors covering behaviors (smoking, heavy alcohol drinking, physical inactivity), diet (low intakes of vegetable and fruit, high intakes of red meat and processed meat), and health conditions (cholelithiasis, chronic liver diseases, diabetes, obesity).
Main outcomes and measures: Incidence of 34 non-sex-specific cancer end points. Attributable rate differences (ARDs, cases per 100 000 person-years) and attributable proportion (AP, %) quantified the number and percentage of the male-female incidence rate gap attributable to the exposures.
Results: Among a total of 589 766 participants (mean [SD] age, 56.1 [8.5] years; 315 813 [53.5%] females), 70 300 non-sex-specific cancer cases were documented. In the Chinese population (134 742 participants [54.4% female]), the joint ARD across the 11 risk factors was 182.52 (95% CI, 162.46-202.26) cases per 100 000 person-years, accounting for 84.44% of the male-female incidence rate difference. Smoking (ARD, 111.87 [95% CI, 95.38-128.00]; AP, 51.75%) and heavy alcohol drinking (ARD, 32.64 [95% CI, 24.61-40.43]; AP, 15.10%) were leading contributors. In the UK population (455 024 participants [53.3% female]), the joint ARD was 52.31 (95% CI, 35.63-70.22) cases per 100 000 person-years, accounting for 26.21% of the sex disparity. Obesity (ARD, 15.34 [95% CI, 6.06-24.08]; AP, 7.68%) and smoking (ARD, 12.49 [95% CI, 1.82-24.39]; AP, 6.26%) were leading individual contributors.
Conclusions and relevance: The findings of this cohort study suggest that modifiable lifestyle factors and health conditions accounted for most of the male-female cancer incidence gap in the Chinese population but only a small fraction in the UK population. Reducing cancer sex disparities may require prevention strategies tailored to population contexts.