Association between levels of sex hormones and risk of esophageal adenocarcinoma and Barrett’s esophagus
Author: Xie, Shao-Hua; Fang, Rui; Huang, Mingtao; Dai, Juncheng; Thrift, Aaron P; Anderson, Lesley A; Chow, Wong-Ho; Bernstein, Leslie; Gammon, Marilie D; Risch, Harvey A; Shaheen, Nicholas J; Reid, Brian J; Wu, Anna H; Iyer, Prasad G; Liu, Geoffrey; Corley, Douglas A; Whiteman, David C; Caldas, Carlos; Pharoah, Paul; Hardie, Laura J; Fitzgerald, Rebecca C; Shen, Hongbing; Vaughan, Thomas L; Lagergren, Jesper
Department: Inst för molekylär medicin och kirurgi / Dept of Molecular Medicine and Surgery
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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 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 standard deviation 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 sulphate, 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.
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 standard deviation 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 sulphate, 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.
Institution:
- Upper Gastrointestinal Surgery, Department of Molecular medicine and Surgery, Karolinska Institutet, 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
- Jiangsu Key Lab of Cancer Biomarkers, Prevention, and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, China
- Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA
- Section of Epidemiology and Population Sciences, Department of Medicine, Baylor College of Medicine, Houston, TX, USA
- Centre for Public Health, Queen's University Belfast, Belfast, UK
- Department of Epidemiology, MD Anderson Cancer Center, Houston, TX, USA
- Department of Population Sciences, Beckman Research Institute and City of Hope Comprehensive Cancer Center, Duarte, CA, USA
- Department of Epidemiology, University of North Carolina Gillings School of Global Public Health, Chapel Hill, NC, USA
- Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA
- Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC, USA
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- Department of Preventive Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
- Pharmacogenomic Epidemiology, Ontario Cancer Institute, Toronto, Ontario, Canada
- Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA
- Cancer Control, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia
- Cancer Research UK, Cambridge Institute, Cambridge, UK
- Department of Oncology, University of Cambridge, Cambridge, UK
- Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
- Division of Epidemiology, Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, Leeds, UK
- Medical Research Council Cancer Unit, Hutchison-Medical Research Council Research Centre, University of Cambridge, Cambridge, UK
- School of Cancer and Pharmaceutical Sciences, King's College London, UK
Citation: Clin Gastroenterol Hepatol. 2020 Nov;18(12):2701-2709.e3.
Citation DOI: 10.1016/j.cgh.2019.11.030
Citation PMID: 31756444
Citation ISI: 000580660700018
Publishing journal: Clinical Gastroenterology and Hepatology
Eprint status: Peer Reviewed
Version: Accepted
Issue date: 2020-03-18
Sponsorship:
- Bengt Ihres Foundation, SLS-78016
- Ruth and Richard Julin Foundation, 2018-00137
- Swedish Research Council, 521-2014-2536, 2015-06275
- Swedish Cancer Society, CAN 2015/460
- National Natural Science Foundation of China, 8151101160
Rights:
CC-BY-NC-ND 4.0
Publication year: 2019
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