Review Sex Hormones, Hormonal Interventions, and Gastric Cancer Risk: A Meta-Analysis

Estrogensmay influence gastric cancer risk, but published studies are inconclusive.We therefore carried out a meta-analysis addressing the associations of gastric cancer in women with menstrual and reproductive factors andwith use of estrogen- and antiestrogen-related therapies. Searches of PubMed up to June, 2011 and reviewof citations yieldeda total of 28 independent studies, including at least one exposure of interest. Random effects pooled estimates of relative risk (RR) and corresponding 95 % CIs were calculated for eight exposures reported in at least five studies, including: age at menarche, age at menopause, years of fertility, parity, age at first birth, oral contraceptive use, hormone replacement therapy (HRT), and tamoxifen treatment. Longer years of fertility (RR 0.74, 95 % CI: 0.63–0.86) and HRT (RR 0.77; 95 % CI: 0.64–0.92) were each associated with decreased gastric cancer risk. Conversely, tamoxifen treatment was associated with increased risk (RR 1.82; 95 % CI: 1.39–2.38). The other five exposures were not significantly associated. Our analysis supports the hypothesis that longer exposure to estrogen effects of either ovarian or exogenous origin may decrease risk of gastric cancer. Additional studies are warranted to extend this finding and to identify the underlying mechanisms. Cancer Epidemiol Biomarkers Prev; 2011 AACR. Background Gastric cancer represents the fourth most common cancer and the second leading cause of cancer death worldwide (1). Notably, for most populations in both high- and low-incidence regions, the overall incidence in males is approximately double that of females (2, 3). Because these sex differences cannot be totally explained by variations in sociodemographic characteristics, envi-ronmental factors, or Helicobacter pylori (H. pylori) infec-tion (4, 5), female sex hormones have been proposed to be protective (6). This hypothesis has been previously eval-uated by examining associations of gastric cancer risk in women with sex hormone–related exposures, but most individual studies have been inconclusive. To more pre-cisely characterize the reported associations, we have done a meta-analysis of these data