Multi-trait genome-wide association study identifies an endometrial cancer risk locus at 7q22.1 that is associated with female testosterone levels

Xuemin Wang, Pik Fang Kho, Dhanya Ramachandran, Cemsel Bafligil, Frederic Amant, Ellen L. Goode, Rodney J. Scott, Ian Tomlinson, D. Gareth Evans, Emma J. Crosbie, Thilo Dörk, Amanda B Spurdle, Dylan M. Glubb, Tracy A. O’mara

Research output: Contribution to journalArticlepeer-review

Abstract

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 randomisation. Following multivariable analysis, five independent risk factors (waist circumference, testosterone levels, sex hormone binding globulin levels, age of menarche and age of 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.
Original languageEnglish
JournaliScience
Publication statusAccepted/In press - 14 Mar 2023

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre

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