Identification of nine new susceptibility loci for endometrial cancer.
Nature communications 2017 ; 9: 3166.
O'Mara TA, Attia J, Auer PL, Beckmann MW, Bolla MK, Brauch H, Brenner H, Burwinkel B, Chang-Claude J, Chanock SJ, Chen C, Couch FJ, Czene K, Dennis J, Dörk T, Fasching PA, García-Closas M, Giles GG, Haiman CA, Hall P, Holliday EG, Hopper JL, Hunter DJ, Kristensen VN, Lambrechts D, Marchand LL, Long J, Lu L, McEvoy M, Meindl A, Michailidou K, Milne RL, Montgomery GW, Orlow I, Perry JR, Peto J, Risch HA, Sacerdote C, Scott RJ, Shah M, Shu XO, Southey MC, Turman C, Tyrer JP, Wang Z, Wentzensen N, Xiang YB, Zheng W, Pharoah PDP, Dunning AM, Kraft P, De Vivo I, Tomlinson I, Easton DF, Spurdle AB, and Thompson DJ
PubMed ID : 30093612
PMCID : PMC6085317
Endometrial cancer is the most commonly diagnosed cancer of the female reproductive tract in developed countries. Through genome-wide association studies (GWAS), we have previously identified eight risk loci for endometrial cancer. Here, we present an expanded meta-analysis of 12,906 endometrial cancer cases and 108,979 controls (including new genotype data for 5624 cases) and identify nine novel genome-wide significant loci, including a locus on 12q24.12 previously identified by meta-GWAS of endometrial and colorectal cancer. At five loci, expression quantitative trait locus (eQTL) analyses identify candidate causal genes; risk alleles at two of these loci associate with decreased expression of genes, which encode negative regulators of oncogenic signal transduction proteins (SH2B3 (12q24.12) and NF1 (17q11.2)). In summary, this study has doubled the number of known endometrial cancer risk loci and revealed candidate causal genes for future study.