Journal
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
Volume 21, Issue 6, Pages 980-987Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1055-9965.EPI-11-1160
Keywords
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Funding
- U.S. PHS [R01 CA092585, R01 CA064277, R01 CA090899, R37 CA070867]
- National Health and Medical Research Council [552402]
- Wellcome Trust
- Cancer Research UK [C1287/A10118, C490/A1021, C8197/A10865, C8197/A10123, C490/A10124]
- Australian Postgraduate Award
- Institute of Health and Biomedical Innovation
- Qld Government Smart State
- Joseph Mitchell Trust
- Oxford Comprehensive Biomedical Research Centre
- Medical Research Council [G0000934]
- Wellcome Trust [068545/Z/02, 085475]
- Deutsche Krebshilfe (German Cancer Aid)
- National Health and Medical Research Council of Australia [339435]
- Cancer Council Queensland [4196615]
- Cancer Council Tasmania [403031, 457636]
- ELAN of the University of Erlangen
- Verelst Foundation for endometrial cancer
- Helse Vest Grant
- University of Bergen
- Melzer Foundation
- Norwegian Cancer Society (Harald Andersens legat)
- Research Council of Norway
- Haukeland University Hospital
- U.S. National Cancer Institute, Division of Cancer Epidemiology and Genetics in the Hormonal and Reproductive Epidemiology Branch
- [075491/Z/04]
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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 silica 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 land H. 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 (Cl), 1.03-1.16] for the A/G genotype and 1.17(95% Cl, 1.05-1.30) for the GIG 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% Cl) 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. Cancer Epidemiol Biomarkers Prev; 21(6); 980-7. (C) 2012 AACR.
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