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Association between Common Germline Genetic Variation in 84 Candidate Genes/Regions and Risks of Ovarian Cancer.

Quaye, L; Tyrer, J; Ramus, SJ; Song, H; Wozniak, E; DiCioccio, RA; McGuire, V; ... Pharoah, PDP; + view all (2009) Association between Common Germline Genetic Variation in 84 Candidate Genes/Regions and Risks of Ovarian Cancer. PLoS One , 4 (6) , Article e5983. 10.1371/journal.pone.0005983. Green open access

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Abstract

Background: Recent studies have identified several single nucleotide polymorphisms (SNPs) in the population that are associated with variations in the risks of many different diseases including cancers such as breast, prostate and colorectal. For ovarian cancer, the known highly penetrant susceptibility genes (BRCA1 and BRCA2) are probably responsible for only 40% of the excess familial ovarian cancer risks, suggesting that other susceptibility genes of lower penetrance exist. Methods: We have taken a candidate approach to identifying moderate risk susceptibility alleles for ovarian cancer. To date, we have genotyped 340 SNPs from 94 candidate genes or regions, in up to 1,491 invasive epithelial ovarian cancer cases and 3,145 unaffected controls from three different population based studies from the UK, Denmark and USA. Results: After adjusting for population stratification by genomic control, 18 SNPs (5.3%) were significant at the 5% level, and 5 SNPs (1.5%) were significant at the 1% level. The most significant association was for the SNP rs2107425, located on chromosome 11p15.5, which has previously been identified as a susceptibility allele for breast cancer from a genome wide association study (P-trend = 0.0012). When SNPs/genes were stratified into 7 different pathways or groups of validation SNPs, the breast cancer associated SNPs were the only group of SNPs that were significantly associated with ovarian cancer risk (P-heterogeneity = 0.0003; P-trend = 0.0028; adjusted (for population stratification) P-trend = 0.006). We did not find statistically significant associations when the combined data for all SNPs were analysed using an admixture maximum likelihood (AML) experiment-wise test for association (P-heterogeneity = 0.051; P-trend = 0.068). Conclusion: These data suggest that a proportion of the SNPs we evaluated were associated with ovarian cancer risk, but that the effect sizes were too small to detect associations with individual SNPs.

Type: Article
Title: Association between Common Germline Genetic Variation in 84 Candidate Genes/Regions and Risks of Ovarian Cancer.
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0005983
Publisher version: http://dx.doi.org/10.1371/journal.pone.0005983
Language: English
Additional information: © 2009 Quaye et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: LQ is funded by the MRC. SJR is funded by the Mermaid component of the Eve Appeal, HS is funded by a grant from WellBeing of Women, DFE is a Principal Research Fellow of Cancer Research UK, PDPP is a Senior Clinical Research Fellow. The research was funded by a Cancer Research UK project grant (no. C8804/A7058). Additional support was provided by the Roswell Park Alliance and the National Cancer Institute (CA71766 and Core Grant CA16056). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Keywords: PlosOne
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health > Womens Cancer
URI: https://discovery.ucl.ac.uk/id/eprint/189242
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