Associations between prediagnostic concentrations of circulating sex steroid hormones and esophageal/gastric cardia adenocarcinoma among men

Jessica L. Petrick, Paula L. Hyland, Patrick Caron, Roni T. Falk, Ruth M. Pfeiffer, Sanford M. Dawsey, Christian C. Abnet, Philip R. Taylor, Stephanie J. Weinstein, Demetrius Albanes, Neal D. Freedman, Susan M. Gapstur, Gary Bradwin, Chantal Guillemette, Peter T. Campbell, Michael B. Cook

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


Background Esophageal adenocarcinoma (EA) and gastric cardia adenocarcinoma (GCA) are characterized by a strong male predominance. Concentrations of 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 in a nested case-control study drawn from participants in three prospective cohort studies. Methods Using gas chromatography-mass spectrometry (GC-MS) and electrochemiluminescence immunoassay, we quantitated sex steroid hormones and sex hormone binding globulin, respectively, in serum from 259 EA/GCA male case participants and 259 matched male control participants from the 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 risk. All statistical tests were two-sided. Results Higher concentrations of dehydroepiandrosterone (DHEA) were associated with a 38% decreased risk of EA/GCA (OR per unit increase in log 2 DHEA = 0.62, 95% CI = 0.47 to 0.82, P trend =.001). Higher estradiol concentrations were associated with a 34% reduced risk of EA/GCA (OR = 0.66, 95% CI = 0.45 to 0.98, P trend =.05), and the association with free estradiol was similar. No other associations between baseline hormone concentrations and future EA/GCA risk were observed. Conclusions This study provides the first evidence that higher concentrations of circulating DHEA, estradiol, and free estradiol may be associated with lower risks of EA/GCA in men.

Original languageEnglish (US)
Article numberdjy082
JournalJournal of the National Cancer Institute
Issue number1
StatePublished - Jan 1 2019
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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