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

Shao Hua Xie, Rui Fang, Mingtao Huang, Juncheng Dai, Aaron P. Thrift, Lesley A. 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

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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 (US)
Pages (from-to)2701-2709.e3
JournalClinical Gastroenterology and Hepatology
Volume18
Issue number12
DOIs
StatePublished - Nov 2020

Keywords

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

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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