Association between circulating levels of sex steroid hormones and esophageal/gastric cardia adenocarcinoma

Authors

• JL Petrick
• PL Hyland
• P Caron
• RT Falk
• R Pfeiffer
• SM Dawsey
• CC Abnet
• PR Taylor
• SJ Weinstein
• D Albanes
• ND Freedman
• G Bradwin
• C Guillemette
• PT Campbell
• MB Cook

Abstract

Objective: Esophageal adenocarcinoma (EA) and gastric cardia adenocarcinoma (GCA) are characterized by a strong male predominance. Sex steroid hormones have been hypothesized to explain this sex disparity. However, no prospective population-based study has examined sex steroid hormones in relation to EA/GCA risk. Thus, we investigated whether prediagnostic circulating sex steroid hormone concentrations were associated with EA/GCA by designing a nested case-control study within three prospective cohort studies. Design: Using gas chromatography-mass spectrometry (GC-MS) and enzyme-linked immunosorbent assay (ELISA), we quantitated sex steroid hormones and sex hormone binding globulin, respectively, in serum from 259 EA/GCA male cases and 259 male controls matched on study, age, race/ethnicity, year of recruitment and time of blood draw from three cohort studies: Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial; Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study; and Cancer Prevention Study II Nutrition Cohort. Multivariable conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between circulating hormones and EA/GCA. Results: Higher levels of dehydroepiandrosterone (DHEA) were associated with a 38% decreased risk of EA/GCA (OR per unit increase in log2 DHEA=0.62, 95% CI=0.47–0.82; Ptrend=0.001). Higher estradiol levels were associated with a 34% reduced risk of EA/GCA (OR=0.66, 95% CI=0.45–0.98; Ptrend=0.05), and the association with free estradiol was similar. No other associations between hormones and future EA/GCA risk were observed. Conclusion: This study provides the first evidence that higher levels of circulating DHEA, estradiol, and free estradiol may be associated with lower risks of EA/GCA.

Scientific Focus Area: Epidemiology

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