Amant, Frederic

Bafligil, Cemsel

Crosbie, Emma J.

Dörk, Thilo

Evans, D. Gareth

Glubb, Dylan M.

Goode, Ellen L.

Kho, Pik Fang

O'Mara, Tracy A.

Ramachandran, Dhanya

Scott, Rodney J

Spurdle, Amanda B

Tomlinson, Ian

Wang, Xuemin

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. </p

Goode, Ellen L

Evans, D Gareth

Crosbie, Emma J

Glubb, Dylan M

O'Mara, Tracy A

The University of Manchester - Institutional Repository

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

Multi-trait GWAS identifies a novel endometrial cancer risk locus that associates with testosterone levels

Multi-trait GWAS identifies a novel endometrial cancer risk locus that associates with testosterone levels

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The University of Manchester - Institutional Repository