Associations Between Sex-Specific Reproductive Factors and Risk of New-Onset Lung Cancer Among Women

Several characteristics distinguish lung cancer in women from that in men, with adenocarcinoma being more prevalent in women and occurring more frequently in women who do not smoke. Uncertainty surrounds the relationship between women-specific reproductive factors and lung cancer risk.Are sex-specific reproductive factors associated with risk of lung cancer in different genetic risk groups and histologic types?A Cox proportional hazard model was used to evaluate the association between multiple reproductive factors and the risk of lung cancer developing in a prospective cohort study involving 273,190 women from the UK Biobank. Subgroup analyses stratified by age, smoking status, BMI, genetic risk, and histologic subtype were conducted to emphasize the modification effects further.A total of 1,182 cases of lung cancer in women were recorded over a median follow-up period of 12.0 years in the cohort study. In multivariable-adjusted models, early menarche (age ≤ 11 years: hazard ratio [HR], 1.22; 95% CI, 1.03-1.46), early menopause (age ≤ 46 years: HR, 1.49; 95% CI, 1.19-1.86), a shorter reproductive span (≤ 32 years: HR, 1.42; 95% CI, 1.18-1.71; and 33-35 years: HR, 1.24; 95% CI, 1.00-1.53), and early age at first birth (age ≤ 20 years: HR, 1.63; 95% CI, 1.33-2.01) were associated with a higher risk of lung cancer. Stratified analysis revealed that several reproductive factors, including early age at menopause, shortened reproductive span, and early age at first birth, showed a substantially stronger relationship with an elevated risk of lung cancer, particularly of lung adenocarcinoma (LUAD), in populations with high genetic risk and more detrimental behaviors.Early age at menopause, a shortened reproductive life span, and early age at first birth were associated with higher risks of lung cancer, particularly of LUAD, in a subpopulation with higher genetic susceptibility and detrimental behaviors. The evidence provided by this study emphasizes the significance of screening for multiple reproductive factors to prevent lung cancer among women.