Female reproductive factors and the risk of gastric cancer in a large-scale population-based cohort study in Japan (JPHC study).

The incidence of gastric cancer is two-fold to three-fold greater in men than in women. We investigated the reasons for this discrepancy by evaluating the impact of female reproductive factors on gastric cancer risk in the Japan Public Health Center-based Prospective Study. Among the 44,453 women enrolled, 368 cases of gastric cancer were newly diagnosed during follow-up from 1990 to 2004. The influence of female reproductive factors on risk was estimated using a multivariable Cox proportional hazards model after adjustment for potential confounders. Participants were stratified by menopause and gastric cancer status and further subdivided by histological type and anatomic subsite. No statistically significant association between female reproductive factors and gastric cancer risk was seen in general. Compared with those in late menarche (> or =15), however, women in early menarche (< or =12) had a close to 50% decreased risk of stomach cancer (hazard ratio 0.65, 95% confidence interval 0.43-0.98; P trend <0.01). Similar results were obtained in subgroup analyses categorized by histological subtype and anatomic subsite. Although early estrogen exposure may have some protective effect, female reproductive factors may have no substantial influence on gastric cancer development.