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JIRONG LONG; WEI ZHENG; DUBROWINSKAJA, Natalia; GOODMAN, MarcT; SALVESEN, Helga B; FASCHING, Peter A; SCOTT, Rodney J; DELAHANTY, Ryan; YING ZHENG; O'MARA, Tracy; HEALEY, Catherine S; HODGSON, Shirley; XIANG, Yong-Bing; RISCH, Harvey; YANG, Hannah P; AMANT, Frederic; TURMANOV, Nurzhan; SCHWAKE, Anita; LURIE, Galina; TROVIK, Jone; BECKMANN, Matthias W; ASHTON, Katie; JI, Bu-Tian; LOSE, Felicity; BAO, Ping-Ping; HOWARTH, Kimberly; LINGENG LU; LISSOWSKA, Jolanta; COENEGRACHTS, Lieve; KAIDAROVA, Dilyara; DÜRST, Matthias; THOMPSON, Pamela J; KRAKSTAD, Camilla; EKICI, Arif B; THOMPSON, Deborah; OTTON, Geoffrey; JIAJUN SHI; BEN ZHANG; GORMAN, Maggie; BRINTON, Louise; COOSEMANS, An; MATSUNO, Rayna K; HALLE, Mari K; HEIN, Alexander; PROIETTO, Anthony; TOMLINSON, Ian; HUI CAI; WEI LU; DUNNING, Alison; EASTON, Douglas; GAO, Yu-Tang; QIUYIN CAI; SPURDLE, Amanda B; SHU, Xiao-Ou; YU, Herbert; WENTZENSEN, Nicolas; LAMBRECHT, Diether; DÖRK, Thilo
Cancer epidemiology, biomarkers & prevention, 06/2012, Letnik: 21, Številka: 6Journal Article
Genome-wide association studies (GWAS) have identified more than 100 genetic loci for various cancers. However, only one is for endometrial cancer. We conducted a three-stage GWAS including 8,492 endometrial cancer cases and 16,596 controls. After analyzing 585,963 single-nucleotide polymorphisms (SNP) in 832 cases and 2,682 controls (stage I) from the Shanghai Endometrial Cancer Genetics Study, we selected the top 106 SNPs for in silico replication among 1,265 cases and 5,190 controls from the Australian/British Endometrial Cancer GWAS (stage II). Nine SNPs showed results consistent in direction with stage I with P < 0.1. These nine SNPs were investigated among 459 cases and 558 controls (stage IIIa) and six SNPs showed a direction of association consistent with stages I and II. These six SNPs, plus two additional SNPs selected on the basis of linkage disequilibrium and P values in stage II, were investigated among 5,936 cases and 8,166 controls from an additional 11 studies (stage IIIb). SNP rs1202524, near the CAPN9 gene on chromosome 1q42.2, showed a consistent association with endometrial cancer risk across all three stages, with ORs of 1.09 95% confidence interval (CI), 1.03-1.16 for the A/G genotype and 1.17 (95% CI, 1.05-1.30) for the G/G genotype (P = 1.6 × 10(-4) in combined analyses of all samples). The association was stronger when limited to the endometrioid subtype, with ORs (95% CI) of 1.11 (1.04-1.18) and 1.21 (1.08-1.35), respectively (P = 2.4 × 10(-5)). Chromosome 1q42.2 may host an endometrial cancer susceptibility locus. This study identified a potential genetic locus for endometrial cancer risk.
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