一项全基因组关联研究在9号染色体短臂22.2区域发现了一个新的卵巢癌易感位点。
A genome-wide association study identifies a new ovarian cancer susceptibility locus on 9p22.2.
作者信息
Song Honglin, Ramus Susan J, Tyrer Jonathan, Bolton Kelly L, Gentry-Maharaj Aleksandra, Wozniak Eva, Anton-Culver Hoda, Chang-Claude Jenny, Cramer Daniel W, DiCioccio Richard, Dörk Thilo, Goode Ellen L, Goodman Marc T, Schildkraut Joellen M, Sellers Thomas, Baglietto Laura, Beckmann Matthias W, Beesley Jonathan, Blaakaer Jan, Carney Michael E, Chanock Stephen, Chen Zhihua, Cunningham Julie M, Dicks Ed, Doherty Jennifer A, Dürst Matthias, Ekici Arif B, Fenstermacher David, Fridley Brooke L, Giles Graham, Gore Martin E, De Vivo Immaculata, Hillemanns Peter, Hogdall Claus, Hogdall Estrid, Iversen Edwin S, Jacobs Ian J, Jakubowska Anna, Li Dong, Lissowska Jolanta, Lubiński Jan, Lurie Galina, McGuire Valerie, McLaughlin John, Medrek Krzysztof, Moorman Patricia G, Moysich Kirsten, Narod Steven, Phelan Catherine, Pye Carole, Risch Harvey, Runnebaum Ingo B, Severi Gianluca, Southey Melissa, Stram Daniel O, Thiel Falk C, Terry Kathryn L, Tsai Ya-Yu, Tworoger Shelley S, Van Den Berg David J, Vierkant Robert A, Wang-Gohrke Shan, Webb Penelope M, Wilkens Lynne R, Wu Anna H, Yang Hannah, Brewster Wendy, Ziogas Argyrios, Houlston Richard, Tomlinson Ian, Whittemore Alice S, Rossing Mary Anne, Ponder Bruce A J, Pearce Celeste Leigh, Ness Roberta B, Menon Usha, Kjaer Susanne Krüger, Gronwald Jacek, Garcia-Closas Montserrat, Fasching Peter A, Easton Douglas F, Chenevix-Trench Georgia, Berchuck Andrew, Pharoah Paul D P, Gayther Simon A
机构信息
Cancer Research UK Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK.
出版信息
Nat Genet. 2009 Sep;41(9):996-1000. doi: 10.1038/ng.424. Epub 2009 Aug 2.
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)).
上皮性卵巢癌具有主要的遗传成分，但已知的易感基因所解释的家族性额外风险不到一半。我们进行了一项全基因组关联研究（GWAS）以鉴定常见的卵巢癌易感等位基因。我们评估了在来自英国的1817例病例和2353例对照中进行基因分型的507,094个单核苷酸多态性（SNP）以及约200万个推算SNP。我们在来自欧洲、美国和澳大利亚的4274例欧洲血统病例和4809例对照中对排名前22,790的SNP进行了基因分型。我们在9p22处鉴定出12个与疾病风险相关的SNP（P < 10^(-8)）。在另外2670例卵巢癌病例和4668例对照中对最显著的SNP（rs3814113；P = 2.5 x 10^(-17)）进行了基因分型，证实了其关联性（合并数据比值比（OR） = 0.82，95%置信区间（CI）0.79 - 0.86，P（趋势） = 5.1 x 10^(-19)）。该关联性在组织学亚型上存在差异，对浆液性卵巢癌最强（OR 0.77，95% CI 0.73 - 0.81，P（趋势） = 4.1 x 10^(-21)）。
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