Endogenous estrogen exposure in relation to distribution of histological type and estrogen receptors in gastric adenocarcinoma

Background. Estrogen might protect women against gastric adenocarcinoma of the intestinal histological type. We addressed this hypothesis and proposed that gastric estrogen receptors (ERs) are involved. Methods. A population-based cohort of patients with gastric adenocarcinoma diagnosed in 1958-2004 in the county of Stockholm was identified through the Swedish Cancer Register. The patients were categorized regarding their endogenous estrogen exposure at diagnosis into: women aged less than 50 years, labelled "exposed women" (n = 364), men aged less than 50 years, labelled "unexposed men" (n = 396), and women aged more than 70 years, labelled "unexposed women" (n = 3008). Tumor specimens were reviewed, and 289 cases were classified into intestinal (n = 101) or diffuse type (n = 188). Cases of intestinal adenocarcinomas (n = 45) were tested for presence of ERalpha, ERbeta, and ERbeta cx by immunohistochemistry. Results. Compared to "exposed women", the intestinal type of gastric adenocarcinoma was more than four times more common among "unexposed men" (odds ratio [OR], 4.7; 95% confidence interval [CI], 2.2-10.3) and nine times more common among "unexposed women" (OR, 9.1; 95% CI, 4.3-19.6). No differences in ER expression were found. A comparison of ERs in tissues taken from the tumors and adjacent gastric mucosa revealed a loss of ERbeta and a gain of ERalpha in the tumor cells. The presence of ERbeta cx was identified for the first time in gastric tumors. Conclusion. Gastric adenocarcinoma of the intestinal type is less common in women with high endogenous estrogen exposure, indicating a preventive effect of estrogen. No differences in the distribution of ERs was found between the three estrogen exposure groups. The presence of ERbeta cx in gastric cancer warrants further investigation.