Jessica Petrick

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NCI, DCEG, HREB

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PLCO (Learn more about this study)

2015-0040

Mar 9, 2015

Pooled analysis of prospective cohort studies: the association between sex steroid hormones and esophageal/gastric cardia adenocarcinoma incidence

Esophageal and gastric cardia adenocarcinoma (EA/GCA) are among the most rapidly increasing cancer types in the U.S. and are often considered as one clinical entity because they are both epithelial cancers originating in or near the gastroesophageal junction. Additionally, EA/GCA incidence in males is approximately 7 times higher than in females. It has been shown that these sex differences are not due solely to established risk factors, such as smoking and obesity. Sex hormones have been hypothesized to potentially account for this sex disparity, but no epidemiological study has been conducted. Previously, members of this study team have employed a strategy to assess sex steroid hormones in relation to Barrett’s esophagus—the pre-neoplastic metaplasia of EA. We found that free testosterone and free dihydrotestosterone were strongly positively associated with Barrett’s esophagus. Testosterone and dihydrotestosterone have been shown to be inversely associated with wound healing, and in the esophagus, this could potentially expand the interval for opportunistic metaplastic re-population.

Given the recognized sex differences of circulating sex steroid hormone concentrations and the fact that so few female cases have accrued in large, mature cohorts, we propose to assess the importance of these hormones in a male-only population. The proposed study will utilize pre-diagnostic serum samples from EA/GCA cases (n=210) and matched controls (n=210) from two prospective studies, the PLCO Trial and the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. We will apply mass spectrometry technologies to quantitate circulating concentrations of androgen and estrogen metabolites. We will use 600 microliters of serum and 10% quality controls to conduct the laboratory analysis.

Odds ratios and 95% confidence intervals will be estimated using conditional logistic regression for associations between EA/GCA and individual sex steroid hormones. This study combines state-of-the-art technology and strong provisional evidence to further elucidate the association between sex steroid hormones and EA/GCA.