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

Abstract

BACKGROUND:

Genome-wide association studies (GWAS) have identified more than 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 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).

RESULTS:

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)).

CONCLUSIONS:

Chromosome 1q42.2 may host an endometrial cancer susceptibility locus.

IMPACT:

This study identified a potential genetic locus for endometrial cancer risk.

• Authors: Jirong Long, Wei Zheng, Yong-Bing Xiang, Felicity Lose, Deborah Thompson, Ian Tomlinson, Herbert Yu, Nicolas Wentzensen, Diether Lambrechts, Thilo Dörk, Natalia Dubrowinskaja, Marc T Goodman, Helga B Salvesen, Peter A Fasching, Rodney J Scott, Ryan Delahanty, Ying Zheng, Tracy O'Mara, Catherine S Healey, Shirley Hodgson, Harvey Risch, Hannah P Yang, Frederic Amant, Nurzhan Turmanov, Anita Schwake, Galina Lurie, Jone Trovik, Matthias W Beckmann, Katie Ashton, Bu-Tian Ji, Ping-Ping Bao, Kimberly Howarth, Lingeng Lu, Jolanta Lissowska, Lieve Coenegrachts, Dilyara Kaidarova, Matthias Dürst, Pamela J Thompson, Camilla Krakstad, Arif B Ekici, Geoffrey Otton, Jiajun Shi, Ben Zhang, Maggie Gorman, Louise Brinton, An Coosemans, Rayna K Matsuno, Mari K Halle, Alexander Hein, Anthony Proietto, Hui Cai, Wei Lu, Alison Dunning, Douglas Easton, Yu-Tang Gao, Qiuyin Cai, Amanda B Spurdle, Xiao-Ou Shu
• Journal: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology (Cancer Epidemiol Biomarkers Prev) Vol. 21 Issue 6 Pg. 980-7 (Jun 2012) ISSN: 1538-7755 [Electronic] United States
• PMID: 22426144 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Topics

• Case-Control Studies
• Chromosomes, Human, Pair 14
• Endometrial Neoplasms (genetics, pathology)
• Female
• Genetic Loci
• Genetic Predisposition to Disease
• Genome-Wide Association Study (methods)
• Humans
• Neoplasm Staging
• Polymorphism, Single Nucleotide
• Risk Factors