Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Department of Epidemiology and Biostatistics, International Joint Research Center on Environment and Human Health, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.
Clin Gastroenterol Hepatol. 2020 Nov;18(12):2701-2709.e3. doi: 10.1016/j.cgh.2019.11.030. Epub 2019 Nov 19.
BACKGROUND & AIMS: Esophageal adenocarcinoma (EAC) occurs most frequently in men. We performed a Mendelian randomization analysis to investigate whether genetic factors that regulate levels of sex hormones are associated with risk of EAC or Barrett's esophagus (BE).
We conducted a Mendelian randomization analysis using data from patients with EAC (n = 2488) or BE (n = 3247) and control participants (n = 2127), included in international consortia of genome-wide association studies in Australia, Europe, and North America. Genetic risk scores or single-nucleotide variants were used as instrumental variables for 9 specific sex hormones. Logistic regression provided odds ratios (ORs) with 95% CIs.
Higher genetically predicted levels of follicle-stimulating hormones were associated with increased risks of EAC and/or BE in men (OR, 1.14 per allele increase; 95% CI, 1.01-1.27) and in women (OR, 1.28; 95% CI, 1.03-1.59). Higher predicted levels of luteinizing hormone were associated with a decreased risk of EAC in men (OR, 0.92 per SD increase; 95% CI, 0.87-0.99) and in women (OR, 0.93; 95% CI, 0.79-1.09), and decreased risks of BE (OR, 0.88; 95% CI, 0.77-0.99) and EAC and/or BE (OR, 0.89; 95% CI, 0.79-1.00) in women. We found no clear associations for other hormones studied, including sex hormone-binding globulin, dehydroepiandrosterone sulfate, testosterone, dihydrotestosterone, estradiol, progesterone, or free androgen index.
In a Mendelian randomization analysis of data from patients with EAC or BE, we found an association between genetically predicted levels of follicle-stimulating and luteinizing hormones and risk of BE and EAC.
食管腺癌（EAC）最常发生于男性。我们进行了一项孟德尔随机分析，以探究调节性激素水平的遗传因素是否与 EAC 或 Barrett 食管（BE）的风险相关。
我们使用来自澳大利亚、欧洲和北美的国际全基因组关联研究联盟中 EAC（n=2488）或 BE（n=3247）患者和对照参与者（n=2127）的数据进行了孟德尔随机分析。遗传风险评分或单核苷酸变异用作 9 种特定性激素的工具变量。逻辑回归提供比值比（OR）及其 95%置信区间（CI）。
较高的遗传预测卵泡刺激素水平与男性（OR，每增加一个等位基因 1.14；95%CI，1.01-1.27）和女性（OR，1.28；95%CI，1.03-1.59）中 EAC 和/或 BE 的风险增加相关。较高的预测黄体生成素水平与男性（OR，SD 每增加 0.92；95%CI，0.87-0.99）和女性（OR，0.93；95%CI，0.79-1.09）中 EAC 的风险降低以及 BE（OR，0.88；95%CI，0.77-0.99）和 EAC 和/或 BE（OR，0.89；95%CI，0.79-1.00）的风险降低相关。我们未发现其他研究的激素存在明显关联，包括性激素结合球蛋白、脱氢表雄酮硫酸酯、睾酮、二氢睾酮、雌二醇、孕酮或游离雄激素指数。
在 EAC 或 BE 患者数据的孟德尔随机分析中，我们发现遗传预测的卵泡刺激素和黄体生成素水平与 BE 和 EAC 的风险之间存在关联。
