Clin Gastroenterol Hepatol. 2019 Nov 19;S1542-3565(19)31317-5. doi: 10.1016/j.cgh.2019.11.030. Online ahead of print.

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.