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

Abstract

Several characteristics distinguish lung cancer in women from that in men, with adenocarcinoma being more prevalent in women and occurring more frequently in nonsmoking women. 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 histological types? A Cox proportional hazard model was used to evaluate the association between multiple reproductive factors and the risk of developing lung cancer in a prospective cohort study involving 273,190 women from the UK Biobank. Subgroup analyses stratified by age, smoking status, body mass index, genetic risk, and histological subtype were conducted to further emphasize the modification effects. A total of 1,182 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: 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; 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, had substantially stronger relationship with an elevated risk of lung cancer, particularly of 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 emphasize the significance of screening for multiple reproductive factors to prevent lung cancer among women.