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A genome-wide association study identifies a new ovarian cancer susceptibility locus on 9p22.2.

Song, Honglin and Ramus, Susan J and Tyrer, Jonathan and Bolton, Kelly L and Gentry-Maharaj, Aleksandra and Wozniak, Eva and Anton-Culver, Hoda and Chang-Claude, Jenny and Cramer, Daniel W and DiCioccio, Richard and Dörk, Thilo and Goode, Ellen L and Goodman, Marc T and Schildkraut, Joellen M and Sellers, Thomas and Baglietto, Laura and Beckmann, Matthias W and Beesley, Jonathan and Blaakaer, Jan and Carney, Michael E and Chanock, Stephen and Chen, Zhihua and Cunningham, Julie M and Dicks, Ed and Doherty, Jennifer A and Dürst, Matthias and Ekici, Arif B and Fenstermacher, David and Fridley, Brooke L and Giles, Graham and Gore, Martin E and De Vivo, Immaculata and Hillemanns, Peter and Hogdall, Claus and Hogdall, Estrid and Iversen, Edwin S and Jacobs, Ian J and Jakubowska, Anna and Li, Dong and Lissowska, Jolanta and Lubiński, Jan and Lurie, Galina and McGuire, Valerie and McLaughlin, John and Medrek, Krzysztof and Moorman, Patricia G and Moysich, Kirsten and Narod, Steven and Phelan, Catherine and Pye, Carole and Risch, Harvey and Runnebaum, Ingo B and Severi, Gianluca and Southey, Melissa and Stram, Daniel O and Thiel, Falk C and Terry, Kathryn L and Tsai, Ya-Yu and Tworoger, Shelley S and Van Den Berg, David J and Vierkant, Robert A and Wang-Gohrke, Shan and Webb, Penelope M and Wilkens, Lynne R and Wu, Anna H and Yang, Hannah and Brewster, Wendy and Ziogas, Argyrios and Houlston, Richard and Tomlinson, Ian and Whittemore, Alice S and Rossing, Mary Anne and Ponder, Bruce A J and Pearce, Celeste Leigh and Ness, Roberta B and Menon, Usha and Kjaer, Susanne Krüger and Gronwald, Jacek and Garcia-Closas, Montserrat and Fasching, Peter A and Easton, Douglas F and Chenevix-Trench, Georgia and Berchuck, Andrew and Pharoah, Paul D P and Gayther, Simon A (2009) A genome-wide association study identifies a new ovarian cancer susceptibility locus on 9p22.2. Nature genetics, 41 (9). pp. 996-1000. ISSN 1546-1718

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Article URL: http://www.nature.com/ng/journal/v41/n9/abs/ng.424...

Abstract

Epithelial ovarian cancer has a major heritable component, but the known susceptibility genes explain less than half the excess familial risk. We performed a genome-wide association study (GWAS) to identify common ovarian cancer susceptibility alleles. We evaluated 507,094 SNPs genotyped in 1,817 cases and 2,353 controls from the UK and approximately 2 million imputed SNPs. We genotyped the 22,790 top ranked SNPs in 4,274 cases and 4,809 controls of European ancestry from Europe, USA and Australia. We identified 12 SNPs at 9p22 associated with disease risk (P < 10(-8)). The most significant SNP (rs3814113; P = 2.5 x 10(-17)) was genotyped in a further 2,670 ovarian cancer cases and 4,668 controls, confirming its association (combined data odds ratio (OR) = 0.82, 95% confidence interval (CI) 0.79-0.86, P(trend) = 5.1 x 10(-19)). The association differs by histological subtype, being strongest for serous ovarian cancers (OR 0.77, 95% CI 0.73-0.81, P(trend) = 4.1 x 10(-21)).

Item Type: Article
Additional Information: This article is available to subscribers only via the URL above.
DOI: 10.1038/ng.424
PubMed ID: 19648919
NIHMSID: NIHMS146644
PMCID: PMC2844110
Grant Numbers: P30 CA016056-33, R01 CA122443-02, P50 CA105009-05, R01 CA054419-15, R01 CA114343-03, R01 CA087538-05, R01 CA112523-04, N01 PC035137, R01 CA058598-10, R01 CA058860-14, K07 CA092044-04
Keywords or MeSH Headings: * Alleles * Australia * Base Sequence * Case-Control Studies * Chromosome Mapping * Chromosomes, Human, Pair 9* * Confidence Intervals * Europe * European Continental Ancestry Group/genetics * European Continental Ancestry Group/statistics & numerical data * Female * Gene Frequency * Genetic Predisposition to Disease* * Genome-Wide Association Study* * Genotype * Haplotypes * Heterozygote * Homozygote * Humans * Linkage Disequilibrium * Molecular Sequence Data * Odds Ratio * Ovarian Neoplasms/genetics* * Ovarian Neoplasms/pathology * Polymorphism, Single Nucleotide * Risk Factors * United States
Subjects: Diseases > Solid tumors > Ovarian cancer
Research Methodologies > Genomics > Gene mapping
Research Methodologies > Epidemiology > Risk assessment
Depositing User: Library Staff
Date Deposited: 17 Sep 2009 18:26
Last Modified: 14 Feb 2012 14:42
URI: http://authors.fhcrc.org/id/eprint/335

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