Cook M B, Wood S, Hyland P L, Caron P, Drahos J, Falk R T, Pfeiffer R M, Dawsey S M, Abnet C C, Taylor P R, Guillemette C, Murray L J, Anderson L A
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA.
Pharmacogenomics Laboratory, Centre Hospitalier de l'Université Laval de Québec (CHU de Québec) Research Center and Faculty of Pharmacy, Laval University, Quebec City, QC, Canada.
Andrology. 2017 Mar;5(2):240-247. doi: 10.1111/andr.12314. Epub 2017 Feb 27.
Previously, we observed strong positive associations between circulating concentrations of free testosterone and free dihydrotestosterone (DHT) in relation to Barrett's esophagus in a US male military population. To replicate these findings, we conducted a second study of sex steroid hormones and Barrett's esophagus in the Factors Influencing the Barrett/Adenocarcinoma Relationship (FINBAR) Study based in Northern Ireland and Ireland. We used mass spectrometry to quantitate EDTA plasma concentrations of nine sex steroid hormones and ELISA to quantitate sex hormone-binding globulin in 177 male Barrett's esophagus cases and 185 male general population controls within the FINBAR Study. Free testosterone, free DHT, and free estradiol were estimated using standard formulas. Multivariable logistic regression estimated odds ratios (OR) and 95% confidence intervals (95%CI) of associations between exposures and Barrett's esophagus. While plasma hormone and sex hormone-binding globulin concentrations were not associated with all cases of Barrett's esophagus, we did observe positive associations with estrogens in younger men (e.g. estrone + estradiol OR = 2.92, 95%CI:1.08, 7.89), and free androgens in men with higher waist-to-hip ratios (e.g. free testosterone OR = 2.71, 95%CI:1.06, 6.92). Stratification by body mass index, antireflux medications, and geographic location did not materially affect the results. This study found evidence for associations between circulating sex steroid hormones and Barrett's esophagus in younger men and men with higher waist-to-hip ratios. Further studies are necessary to elucidate whether sex steroid hormones are consistently associated with esophageal adenocarcinogenesis.
此前,我们在美国男性军人人群中观察到,游离睾酮和游离双氢睾酮(DHT)的循环浓度与巴雷特食管之间存在很强的正相关。为了重复这些发现,我们在北爱尔兰和爱尔兰开展的影响巴雷特食管/腺癌关系的因素(FINBAR)研究中,进行了第二项关于性类固醇激素与巴雷特食管的研究。我们使用质谱法定量分析了177例男性巴雷特食管病例和185例男性普通人群对照的乙二胺四乙酸(EDTA)血浆中9种性类固醇激素的浓度,并使用酶联免疫吸附测定法(ELISA)定量分析了性激素结合球蛋白。游离睾酮、游离DHT和游离雌二醇通过标准公式估算。多变量逻辑回归分析估计了暴露因素与巴雷特食管之间关联的比值比(OR)和95%置信区间(95%CI)。虽然血浆激素和性激素结合球蛋白浓度与所有巴雷特食管病例均无关联,但我们确实观察到,在年轻男性中,雌激素与之存在正相关(例如,雌酮+雌二醇OR = 2.92,95%CI:1.08,7.89),在腰臀比更高的男性中,游离雄激素与之存在正相关(例如,游离睾酮OR = 2.71,95%CI:1.06,6.92)。按体重指数、抗反流药物和地理位置分层并未对结果产生实质性影响。本研究发现,循环性类固醇激素与年轻男性及腰臀比更高的男性的巴雷特食管之间存在关联。有必要进一步开展研究,以阐明性类固醇激素是否始终与食管腺癌发生相关。