GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer
Author(s)
Type
Journal Article
Abstract
Genome-wide association studies (GWAS) have identified four susceptibility loci for epithelial ovarian cancer (EOC), with another two suggestive loci reaching near genome-wide significance. We pooled data from a GWAS conducted in North America with another GWAS from the UK. We selected the top 24,551 SNPs for inclusion on the iCOGS custom genotyping array. We performed follow-up genotyping in 18,174 individuals with EOC (cases) and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. We validated the two loci at 3q25 and 17q21 that were previously found to have associations close to genome-wide significance and identified three loci newly associated with risk: two loci associated with all EOC subtypes at 8q21 (rs11782652, P = 5.5 × 10−9) and 10p12 (rs1243180, P = 1.8 × 10−8) and another locus specific to the serous subtype at 17q12 (rs757210, P = 8.1 × 10−10). An integrated molecular analysis of genes and regulatory regions at these loci provided evidence for functional mechanisms underlying susceptibility and implicated CHMP4C in the pathogenesis of ovarian cancer.
Date Issued
2013-03-27
Date Acceptance
2013-01-30
Citation
Nature Genetics, 2013, 45 (4), pp.362-370
ISSN
1546-1718
Publisher
Nature Publishing Group
Start Page
362
End Page
370
Journal / Book Title
Nature Genetics
Volume
45
Issue
4
Copyright Statement
© 2013 Nature America, Inc. All rights reserved.
Sponsor
Cancer Research UK
Grant Number
C536/A13086
Subjects
Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
GENETICS & HEREDITY
GENOME-WIDE ASSOCIATION
RISK
GENE
EXPRESSION
CARCINOMA
NEBULETTE
LEUKEMIA
CELLS
19P13
MYC
Case-Control Studies
Cooperative Behavior
Cystadenocarcinoma, Serous
Female
Gene-Environment Interaction
Genetic Loci
Genetic Predisposition to Disease
Genome-Wide Association Study
Genotype
Humans
Meta-Analysis as Topic
Neoplasm Invasiveness
Ovarian Neoplasms
Polymorphism, Single Nucleotide
Risk Factors
Australian Cancer Study
Australian Ovarian Cancer Study Group
Developmental Biology
11 Medical And Health Sciences
06 Biological Sciences
Publication Status
Published