Abstract

Abstract Background: There is a 23-fold difference in gastric cancer incidence worldwide between high- and low-risk populations. In all regions, gastric cancer incidence is two-fold higher among men, compared with women. Although higher prevalence of established risk factors in men may explain some of the sex disparity, a protective role of high lifelong exposure to estrogens may contribute to the lower gastric cancer incidence for women. There have been few prospective data evaluating associations with gastric cancer risk for markers of estrogen exposure in high-risk populations. Methods: In the Singapore Chinese Health Study, 34,022 women between 45 and 74 years of age were recruited as cohort participants between 1993 and 1998. By December 2013, 315 incident gastric cancer cases were identified. Information about menstrual and reproductive histories, as well as oral contraceptive (OC) and hormone replacement therapy (HRT) use was collected at the baseline interview. Cox proportional hazard regression was performed to obtain the adjusted hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for menstrual and reproductive factors and exogenous hormone use with gastric cancer risk. In secondary analyses, a nested case-control study was conducted in which Helicobacter (H.) pylori infection and atrophic gastritis status were evaluated in conditional logistic regression models as potential confounders on the association between hormone-related factors and gastric cancer risk. Results: Compared with nonusers, ever use of HRT (HR = 0.55; 95%CI: 0.26, 1.18), OCs (HR = 0.69; 95%CI: 0.51, 0.95) and HRT and/or OCs (HR = 0.67; 95%CI: 0.49-0.92) was associated with a lower risk of gastric cancer. A statistically significant trend with increasing age at first OC use was observed for gastric cancer risk, compared with nonusers (P for trend = 0.013). The HRs (95% CIs) for ≤25, 26-30 and >30 years of age, compared with nonusers were 0.85 (0.50, 1.46), 0.76 (0.48, 1.21), and 0.54 (0.31, 0.92), respectively. There were no associations with other menstrual or reproductive factors including number of births, years of menstrual cycling, or age at menopause. The inverse associations with ever HRT and/or OC use for gastric cancer risk remained after further adjusting for H. pylori infection and atrophic gastritis status. Conclusion: In a high-risk study population, ever use of exogenous hormones was associated with a statistically significant decrease in gastric cancer risk, independent of established risk factors. These results support the notion that high exposure to estrogens may contribute to the lower incidence of gastric cancer in women compared with men. Citation Format: Zhensheng Wang, Anna H. Wu, Woon-Puay Koh, Aizhen Jin, Renwei Wang, Jian-Min Yuan, Lesley M. Butler. Exogenous hormone use was inversely associated with gastric cancer risk among women: The Singapore Chinese Health Study. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 863. doi:10.1158/1538-7445.AM2015-863

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