Petrick Jessica L, Falk Roni T, Hyland Paula L, Caron Patrick, Pfeiffer Ruth M, Wood Shannon N, Dawsey Sanford M, Abnet Christian C, Taylor Philip R, Guillemette Chantal, Murray Liam J, Anderson Lesley A, Cook Michael B
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland, United States of America.
Pharmacogenomics Laboratory, Centre Hospitalier de l'Université Laval de Québec (CHU de Québec) Research Center and Faculty of Pharmacy, Laval University, Québec City, Québec, Canada.
PLoS One. 2018 Jan 17;13(1):e0190325. doi: 10.1371/journal.pone.0190325. eCollection 2018.
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.
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.
Higher androgen:estrogen ratio metrics were associated with increased odds of EA (e.g., testosterone:estradiol ratio ORQ4 v. Q1 = 2.58, 95%CI = 1.23-5.43; Ptrend = 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.
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.
食管腺癌(EA)具有明显的男性优势。有假说认为性类固醇激素是这种性别差异的基础,但迄今为止尚无基于人群的研究探讨这种潜在关联。
在北爱尔兰和爱尔兰进行的一项病例对照研究——影响巴雷特食管/腺癌关系的因素(FINBAR)研究中,我们分别使用质谱分析法和酶联免疫吸附测定法(ELISA)对172例EA男性病例和185例对照男性的血浆中性类固醇激素和性激素结合球蛋白进行了定量分析。采用多变量调整逻辑回归计算循环激素与EA之间关联的比值比(OR)和95%置信区间(CI)。
较高的雄激素:雌激素比值指标与EA发病几率增加相关(例如,睾酮:雌二醇比值,四分位数4对比四分位数1,OR = 2.58,95%CI = 1.23 - 5.43;P趋势 = 0.009)。所有雌激素和雄激素均与EA发病几率显著降低相关。当仅限于体重指数降低极少或未降低的个体时,雄激素:雌激素比值的关联大小变化不大。
这项关于性类固醇激素与EA的首次研究提供了初步证据,表明雄激素:雌激素平衡可能是与EA相关的一个因素。需要在前瞻性研究中重复这些发现,以增强对这种效应因果关系的信心。