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

doi:10.1158/1055-9965.EPI-11-1160

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

by Jirong Long, Wei Zheng, Yong-bing Xiang, Felicity A Lose, Deborah J Thompson, … Ian Tomlinson, Herbert Yu, Nicolas Wentzensen, Diether Lambrechts, Thilo Dork, Natalia Dubrowinskaja, Marc T Goodman, Helga Salvesen, Peter A Fasching, Rodney J Scott, Ryan Delahanty, Ying Zheng, Tracy A O'Mara, Catherine S Healey, Shirley V Hodgson, Harvey Risch, Hannah P Yang, Frederic Amant, Nurzhan Turmanov, Anita Schwake, Galina Lurie, Jone Trovik, Matthias W Beckmann, Katie A Ashton, Butian Ji, Ping-Ping Bao, Kimberley Howarth, Lingeng Lu, Jolanta Lissowska, Lieve Coenegrachts, Dilyara Kaidarova, Matthias Durst, Pamela J Thompson, Camilla Krakstad, Arif B Ekici, Geoffrey Otton, Jiajun Shi, Ben Zhang, Maggie Gorman, Louise A Brinton, An Coosemans, Rayna K Matsuno, Mari Halle, Alexander Hein, Anthony Proietto, Hui Cai, Wei Lu, Alison Dunning, Douglas F Easton, Yu-Tang Gao, Qiuyin Cai, Amanda B Spurdle, Xiao-Ou Shu show all authors

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Cancer Epidemiology Biomarkers Prevention (2012)

ISSN: 15387755
DOI: 10.1158/1055-9965.EPI-11-1160
PubMed: 22426144

Available from Cancer Epidemiology Biomarkers Prevention

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Abstract

BACKGROUND: Genome-wide association studies (GWAS) have identified over 100 genetic loci for various cancers. However, only one is for endometrial cancer. METHODS: We conducted a three-stage GWAS including 8,492 endometrial cancer cases and 16,596 controls. After analyzing 585,963 SNPs in 832 cases and 2,682 controls (Stage 1) 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 2). Nine SNPs showed results consistent in direction with Stage 1 with P<0.1. These 9 SNPs were investigated among 459 cases and 558 controls (Stage 3a) and 6 SNPs showed a direction of association consistent with Stages 1 and 2. These 6 SNPs, plus 2 additional SNPs selected based on linkage disequilibrium (LD) and P values in Stage 2, were investigated among 5,936 cases and 8,166 controls from an additional 11 studies (Stage 3b). RESULTS: SNP rs1202524, near the CAPN9 gene on chromosome 1q42.2, showed a consistent association with endometrial cancer risk across all three stages, with odds ratios (OR) of 1.09 (95% 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 x 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 x 10-5). CONCLUSIONS: Chromosome 1q42.2 may host an endometrial cancer susceptibility locus. IMPACT: This study identified a potential genetic locus for endometrial cancer risk.