Association Between Levels of Sex Hormones and Risk of Esophageal Adenocarcinoma and Barrett’s Esophagus

Shao-Hua Xie* (Corresponding Author), Rui Fang, Mingtao Huang, Juncheng Dai, Aaron Thrift, Lesley Anderson, Wong-Ho Chow, Leslie Bernstein, Marilie D Gammon, Harvey A Risch, Nicholas J Shaheen, Brian J Reid, Anna H Wu, Prasad G Iyer, Geoffrey Liu, Douglas A Corley, David C Whiteman, Carlos Caldas, Paul D. Pharoah, Laura J HardieRebecca C. Fitzgerald, Hongbing Shen, Thomas L Vaughan, Jesper Lagergren

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

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.
Original languageEnglish
JournalClinical Gastroenterology and Hepatology
Early online date19 Nov 2019
DOIs
Publication statusE-pub ahead of print - 19 Nov 2019

Keywords

  • Esophageal Neoplasms
  • Sex Difference
  • Gonadal Steroid
  • Hormones
  • Causality

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    Xie, S-H., Fang, R., Huang, M., Dai, J., Thrift, A., Anderson, L., Chow, W-H., Bernstein, L., Gammon, M. D., Risch, H. A., Shaheen, N. J., Reid, B. J., Wu, A. H., Iyer, P. G., Liu, G., Corley, D. A., Whiteman, D. C., Caldas, C., Pharoah, P. D., ... Lagergren, J. (2019). Association Between Levels of Sex Hormones and Risk of Esophageal Adenocarcinoma and Barrett’s Esophagus. Clinical Gastroenterology and Hepatology. https://doi.org/10.1016/j.cgh.2019.11.030