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


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)).

SUBMITTER: Song H 

PROVIDER: S-EPMC2844110 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

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

Song Honglin H   Ramus Susan J SJ   Tyrer Jonathan J   Bolton Kelly L KL   Gentry-Maharaj Aleksandra A   Wozniak Eva E   Anton-Culver Hoda H   Chang-Claude Jenny J   Cramer Daniel W DW   DiCioccio Richard R   Dörk Thilo T   Goode Ellen L EL   Goodman Marc T MT   Schildkraut Joellen M JM   Sellers Thomas T   Baglietto Laura L   Beckmann Matthias W MW   Beesley Jonathan J   Blaakaer Jan J   Carney Michael E ME   Chanock Stephen S   Chen Zhihua Z   Cunningham Julie M JM   Dicks Ed E   Doherty Jennifer A JA   Dürst Matthias M   Ekici Arif B AB   Fenstermacher David D   Fridley Brooke L BL   Giles Graham G   Gore Martin E ME   De Vivo Immaculata I   Hillemanns Peter P   Hogdall Claus C   Hogdall Estrid E   Iversen Edwin S ES   Jacobs Ian J IJ   Jakubowska Anna A   Li Dong D   Lissowska Jolanta J   Lubiński Jan J   Lurie Galina G   McGuire Valerie V   McLaughlin John J   Medrek Krzysztof K   Moorman Patricia G PG   Moysich Kirsten K   Narod Steven S   Phelan Catherine C   Pye Carole C   Risch Harvey H   Runnebaum Ingo B IB   Severi Gianluca G   Southey Melissa M   Stram Daniel O DO   Thiel Falk C FC   Terry Kathryn L KL   Tsai Ya-Yu YY   Tworoger Shelley S SS   Van Den Berg David J DJ   Vierkant Robert A RA   Wang-Gohrke Shan S   Webb Penelope M PM   Wilkens Lynne R LR   Wu Anna H AH   Yang Hannah H   Brewster Wendy W   Ziogas Argyrios A   Houlston Richard R   Tomlinson Ian I   Whittemore Alice S AS   Rossing Mary Anne MA   Ponder Bruce A J BA   Pearce Celeste Leigh CL   Ness Roberta B RB   Menon Usha U   Kjaer Susanne Krüger SK   Gronwald Jacek J   Garcia-Closas Montserrat M   Fasching Peter A PA   Easton Douglas F DF   Chenevix-Trench Georgia G   Berchuck Andrew A   Pharoah Paul D P PD   Gayther Simon A SA  

Nature genetics 20090802 9


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 Austral  ...[more]

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