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Genome-wide association study identifies a possible susceptibility locus for endometrial cancer.


ABSTRACT: 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.

SUBMITTER: Long J 

PROVIDER: S-EPMC3372671 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Genome-wide association study identifies a possible susceptibility locus for endometrial cancer.

Long Jirong J   Zheng Wei W   Xiang Yong-Bing YB   Lose Felicity F   Thompson Deborah D   Tomlinson Ian I   Yu Herbert H   Wentzensen Nicolas N   Lambrechts Diether D   Dörk Thilo T   Dubrowinskaja Natalia N   Goodman Marc T MT   Salvesen Helga B HB   Fasching Peter A PA   Scott Rodney J RJ   Delahanty Ryan R   Zheng Ying Y   O'Mara Tracy T   Healey Catherine S CS   Hodgson Shirley S   Risch Harvey H   Yang Hannah P HP   Amant Frederic F   Turmanov Nurzhan N   Schwake Anita A   Lurie Galina G   Trovik Jone J   Beckmann Matthias W MW   Ashton Katie K   Ji Bu-Tian BT   Bao Ping-Ping PP   Howarth Kimberly K   Lu Lingeng L   Lissowska Jolanta J   Coenegrachts Lieve L   Kaidarova Dilyara D   Dürst Matthias M   Thompson Pamela J PJ   Krakstad Camilla C   Ekici Arif B AB   Otton Geoffrey G   Shi Jiajun J   Zhang Ben B   Gorman Maggie M   Brinton Louise L   Coosemans An A   Matsuno Rayna K RK   Halle Mari K MK   Hein Alexander A   Proietto Anthony A   Cai Hui H   Lu Wei W   Dunning Alison A   Easton Douglas D   Gao Yu-Tang YT   Cai Qiuyin Q   Spurdle Amanda B AB   Shu Xiao-Ou XO  

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20120316 6


<h4>Background</h4>Genome-wide association studies (GWAS) have identified more than 100 genetic loci for various cancers. However, only one is for endometrial cancer.<h4>Methods</h4>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  ...[more]

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