Multi-trait genome-wide association study identifies a novel endometrial cancer risk locus that associates with testosterone levels.

Autor:	Wang X; Cancer Research Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia., Kho PF; Cancer Research Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia., Ramachandran D; Gynaecology Research Unit, Hannover Medical School, 30625 Hannover, Germany., Bafligil C; Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, St Mary's Hospital, Manchester M13 9WL, UK.; Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9WL, UK., Amant F; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University Hospitals KU Leuven, University of Leuven, 3000 Leuven, Belgium., Goode EL; Department of Quantitative Health Sciences, Division of Epidemiology, Mayo Clinic, Rochester, MN 55905, USA., Scott RJ; Division of Molecular Medicine, Pathology North, John Hunter Hospital, Newcastle, NSW 2305, Australia.; Discipline of Medical Genetics, School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle, Callaghan, NSW 2308, Australia.; Hunter Medical Research Institute, John Hunter Hospital, Newcastle, NSW 2305, Australia., Tomlinson I; Cancer Genetics and Evolution Laboratory, Cancer Research UK Edinburgh Centre, MRC Institute of Genetics & Molecular Medicine, The University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XR, UK., Evans DG; Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9WL, UK.; North West Genomics Laboratory Hub, Manchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9WL, UK., Crosbie EJ; Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, St Mary's Hospital, Manchester M13 9WL, UK.; Department of Obstetrics and Gynaecology, St Mary's Hospital, Manchester Academic Health Science Centre, Manchester University NHS Foundation Trust, Manchester M13 9WL, UK., Dörk T; Gynaecology Research Unit, Hannover Medical School, 30625 Hannover, Germany., Spurdle AB; Population Health Research Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia., Glubb DM; Cancer Research Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia.; School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia.; School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD 4000, Australia., O'Mara TA; Cancer Research Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia.; School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia.; School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD 4000, Australia.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2023 Apr 07; Vol. 26 (5), pp. 106590. Date of Electronic Publication: 2023 Apr 07 (Print Publication: 2023).
DOI:	10.1016/j.isci.2023.106590
Abstrakt:	To detect novel endometrial cancer risk variants, we leveraged information from endometrial cancer risk factors in a multi-trait GWAS analysis. We first assessed causal relationships between established and suspected endometrial cancer risk factors, and endometrial cancer using Mendelian randomization. Following multivariable analysis, five independent risk factors (waist circumference, testosterone levels, sex hormone binding globulin levels, age at menarche, and age at natural menopause) were included in a multi-trait Bayesian GWAS analysis. We identified three potentially novel loci that associate with endometrial cancer risk, one of which (7q22.1) replicated in an independent endometrial cancer GWAS dataset and was genome-wide significant in a meta-analysis. This locus may affect endometrial cancer risk through altered testosterone levels. Consistent with this, we observed colocalization between the signals for endometrial cancer risk and expression of CYP3A7 , a gene involved in testosterone metabolism. Thus, our findings suggest opportunities for hormone therapy to prevent or treat endometrial cancer. Competing Interests: The authors declare no competing interests. (© 2023 The Author(s).)
Databáze:	MEDLINE
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