Association Between Levels of Hormones and Risk of Esophageal Adenocarcinoma and Barrett's Esophagus
Shao-Hua Xie 1 , Rui Fang 2 , Mingtao Huang 2 , Juncheng Dai 3 , Aaron P Thrift 4 , Lesley A Anderson 5 , Wong-Ho Chow 6 , Leslie Bernstein 7 , Marilie D Gammon 8 , Harvey A Risch 9 , Nicholas J Shaheen 10 , Brian J Reid 11 , Anna H Wu 12 , Prasad G Iyer 13 , Geoffrey Liu 14 , Douglas A Corley 15 , David C Whiteman 16 , Carlos Caldas 17 , Paul D Pharoah 18 , Laura J Hardie 19 , Rebecca C Fitzgerald 20 , Hongbing Shen 3 , Thomas L Vaughan 11 , Jesper Lagergren 21
PMID: 31756444 DOI: 10.1016/j.cgh.2019.11.030
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).
Methods: 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.
Results: 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.
Conclusions: 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.
Keywords: Causality; Esophageal Neoplasms; Gonadal Steroid Hormones; Sex Difference.
Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.