Association between circulating levels of sex steroid hormones and esophageal adenocarcinoma in the FINBAR Study

Background Esophageal adenocarcinoma (EA) is characterized by a strong male predominance. Sex steroid hormones have been hypothesized to underlie this sex disparity, but no population-based study to date has examined this potential association. Methods Using mass spectrometry and ELISA, we quantitated sex steroid hormones and sex hormone binding globulin, respectively, in plasma from males- 172 EA cases and 185 controls-within the Factors Influencing the Barrett/Adenocarcinoma Relationship (FINBAR) Study, a case-control investigation conducted in Northern Ireland and Ireland. Multivariable adjusted logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between circulating hormones and EA. Results Higher androgen: estrogen ratio metrics were associated with increased odds of EA (e.g., testosterone: estradiol ratio ORQ4v.Q1 = 2.58, 95% CI = 1.23-5.43; P-trend = 0.009). All estrogens and androgens were associated with significant decreased odds of EA. When restricted to individuals with minimal to no decrease in body mass index, the size of association for the androgen: estrogen ratio was not greatly altered. Conclusions This first study of sex steroid hormones and EA provides tentative evidence that androgen: estrogen balance may be a factor related to EA. Replication of these findings in prospective studies is needed to enhance confidence in the causality of this effect.