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RISS 인기검색어
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- 저자 : Struewing, Jeffery P. (검색결과 2 건)
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Udler, Miriam S,Meyer, Kerstin B,Pooley, Karen A,Karlins, Eric,Struewing, Jeffery P,Zhang, Jinghui,Doody, David R,MacArthur, Stewart,Tyrer, Jonathan,Pharoah, Paul D,Luben, Robert,Bernstein, Leslie,Kol IRL Press ; Oxford University Press 2009 Human Molecular Genetics Vol.18 No.9
<P>Genome-wide association studies have identified FGFR2 as a breast cancer (BC) susceptibility gene in populations of European and Asian descent, but a causative variant has not yet been conclusively identified. We hypothesized that the weaker linkage disequilibrium across this associated region in populations of African ancestry might help refine the set of candidate-causal single nucleotide polymorphisms (SNPs) previously identified by our group. Eight candidate-causal SNPs were evaluated in 1253 African American invasive BC cases and 1245 controls. A significant association with BC risk was found with SNP rs2981578 (unadjusted per-allele odds ratio = 1.20, 95% confidence interval 1.03-1.41, P(trend) = 0.02), with the odds ratio estimate similar to that reported in European and Asian subjects. To extend the fine-mapping, genotype data from the African American studies were analyzed jointly with data from European (n = 7196 cases, 7275 controls) and Asian (n = 3901 cases, 3205 controls) studies. In the combined analysis, SNP rs2981578 was the most strongly associated. Five other SNPs were too strongly correlated to be excluded at a likelihood ratio of < 1/100 relative to rs2981578. Analysis of DNase I hypersensitive sites indicated that only two of these map to highly accessible chromatin, one of which, SNP rs2981578, has previously been implicated in up-regulating FGFR2 expression. Our results demonstrate that the association of SNPs in FGFR2 with BC risk extends to women of African American ethnicity, and illustrate the utility of combining association analysis in datasets of diverse ethnic groups with functional experiments to identify disease susceptibility variants.</P>
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Genome-wide association study identifies novel breast cancer susceptibility loci
Easton, Douglas F.,Pooley, Karen A.,Dunning, Alison M.,Pharoah, Paul D. P.,Thompson, Deborah,Ballinger, Dennis G.,Struewing, Jeffery P.,Morrison, Jonathan,Field, Helen,Luben, Robert,Wareham, Nicholas Nature Publishing Group 2007 Nature Vol.447 No.7148
Breast cancer exhibits familial aggregation, consistent with variation in genetic susceptibility to the disease. Known susceptibility genes account for less than 25% of the familial risk of breast cancer, and the residual genetic variance is likely to be due to variants conferring more moderate risks. To identify further susceptibility alleles, we conducted a two-stage genome-wide association study in 4,398 breast cancer cases and 4,316 controls, followed by a third stage in which 30 single nucleotide polymorphisms (SNPs) were tested for confirmation in 21,860 cases and 22,578 controls from 22 studies. We used 227,876 SNPs that were estimated to correlate with 77% of known common SNPs in Europeans at r<SUP>2</SUP> > 0.5. SNPs in five novel independent loci exhibited strong and consistent evidence of association with breast cancer (P < 10<SUP>-7</SUP>). Four of these contain plausible causative genes (FGFR2, TNRC9, MAP3K1 and LSP1). At the second stage, 1,792 SNPs were significant at the P < 0.05 level compared with an estimated 1,343 that would be expected by chance, indicating that many additional common susceptibility alleles may be identifiable by this approach.
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