Reproductive factors and lung cancer risk: a comprehensive systematic review and meta-analysis

Background A number of studies have investigated the association between reproductive factors and lung cancer risk, however findings are inconsistent. This meta-analysis aimed to evaluate the association between female reproductive factors and lung cancer risk. Methods We conducted a comprehensive systematic search to identify relevant and eligible studies published before 18th December 2019. Inter-study heterogeneity was assessed using theQtest andI(2)statistic. Based on the heterogeneity of each reproductive factor, fixed or random effects models were used to calculate the summary odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses by study design, lung cancer subtypes, smoking status, and ethnicity were also performed. Results A total of 66 studies with 20 distinct reproductive factors were included in this meta-analysis. Comparing the highest and lowest categories (reference) of each reproductive factor, parity (OR = 0.83, 95% CI = 0.72-0.96), menstrual cycle length (OR = 0.79, 95% CI = 0.65-0.96), and age at first birth (OR = 0.85, 95% CI = 0.74-0.98), were significantly associated with a lower risk of overall lung cancer. On the contrary, non-natural menopause was significantly associated with higher lung cancer risk (OR = 1.52, 95% CI = 1.25-1.86). Among never-smokers, a significant negative association was found between parity and lung cancer risk. Both parity and non-natural menopause were statistically significant in case-control studies. Conclusion These results suggest that certain reproductive factors may be associated with lung cancer risk. Future studies should further validate the associations, and investigate the underlying mechanisms.