Abstract
BACKGROUND: Female menstrual and reproductive factors, as remarkable indicators of hormone effect, were hypothesized to be associated with lung cancer risk, whereas the existed epidemiological evidence was inconsistent. Our study aims to investigate the association between menstrual and reproductive factors and lung cancer risk based on the Chinese Lung Cancer Screening Program. METHODS: This study was based on a large-scale multi-center population cohort across China recruiting individuals aged 40-74 years old between 2013-2018. Cox regression model was applied to estimate the HRs and 95% CIs. Restricted cubic spline (RCS) analysis was used to estimate dose-response relationships and test for nonlinear associations. RESULTS: Among 553,434 female participants, 1,529 incident lung cancer cases were identified with a median follow-up of 3.61 years. With adjustment for multiple covariates and all significant hormonal factors, elevated lung cancer risk was associated with later age (15, or ≥16 years) at menarche (HR =1.27, 95% CI: 1.04-1.56; HR =1.45, 95% CI: 1.19-1.76), later age (25-29, or ≥30 years) at first live birth (HR =1.27, 95% CI: 1.13-1.43; HR =1.23, 95% CI: 1.00-1.51), and benign breast disease history (HR =1.25, 95% CI: 1.10-1.41). For postmenopausal females specifically, surgical menopause (HR =1.62; 95% CI: 1.29-2.05) and other surgeries on the reproductive system (HR =1.19; 95% CI: 1.01-1.40) both appeared to be predictive of elevated lung cancer risk. Concerning age at menopause, a nonlinear association was observed (P-nonlinear =0.0126). Increased lung cancer risk was observed among females with age at menopause especially above 50. Although we observed no significant associations between longer time (≥13 months) of breastfeeding and lung cancer risk among all participants (HR =0.86; 95% CI: 0.71-1.04), significant decreased adenocarcinoma risk (HR =0.65; 95% CI: 0.53-0.81) was noted among nonsmoking females. CONCLUSIONS: Our findings add some support for the role of menstrual and reproductive factors in lung carcinogenesis. However, these relationships were complex, and required further investigations addressing the biological mechanisms.