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A multistage genome-wide association study in breast cancer identifies two new risk alleles at 1p11.2 and 14q24.1 (RAD51L1).

ABSTRACT: We conducted a three-stage genome-wide association study (GWAS) of breast cancer in 9,770 cases and 10,799 controls in the Cancer Genetic Markers of Susceptibility (CGEMS) initiative. In stage 1, we genotyped 528,173 SNPs in 1,145 cases of invasive breast cancer and 1,142 controls. In stage 2, we analyzed 24,909 top SNPs in 4,547 cases and 4,434 controls. In stage 3, we investigated 21 loci in 4,078 cases and 5,223 controls. Two new loci achieved genome-wide significance. A pericentromeric SNP on chromosome 1p11.2 (rs11249433; P = 6.74 x 10(-10) adjusted genotype test, 2 degrees of freedom) resides in a large linkage disequilibrium block neighboring NOTCH2 and FCGR1B; this signal was stronger for estrogen-receptor-positive tumors. A second SNP on chromosome 14q24.1 (rs999737; P = 1.74 x 10(-7)) localizes to RAD51L1, a gene in the homologous recombination DNA repair pathway. We also confirmed associations with loci on chromosomes 2q35, 5p12, 5q11.2, 8q24, 10q26 and 16q12.1.

SUBMITTER: Thomas G 

PROVIDER: S-EPMC2928646 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

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A multistage genome-wide association study in breast cancer identifies two new risk alleles at 1p11.2 and 14q24.1 (RAD51L1).

Thomas Gilles G   Jacobs Kevin B KB   Kraft Peter P   Yeager Meredith M   Wacholder Sholom S   Cox David G DG   Hankinson Susan E SE   Hutchinson Amy A   Wang Zhaoming Z   Yu Kai K   Chatterjee Nilanjan N   Garcia-Closas Montserrat M   Gonzalez-Bosquet Jesus J   Prokunina-Olsson Ludmila L   Orr Nick N   Willett Walter C WC   Colditz Graham A GA   Ziegler Regina G RG   Berg Christine D CD   Buys Saundra S SS   McCarty Catherine A CA   Feigelson Heather Spencer HS   Calle Eugenia E EE   Thun Michael J MJ   Diver Ryan R   Prentice Ross R   Jackson Rebecca R   Kooperberg Charles C   Chlebowski Rowan R   Lissowska Jolanta J   Peplonska Beata B   Brinton Louise A LA   Sigurdson Alice A   Doody Michele M   Bhatti Parveen P   Alexander Bruce H BH   Buring Julie J   Lee I-Min IM   Vatten Lars J LJ   Hveem Kristian K   Kumle Merethe M   Hayes Richard B RB   Tucker Margaret M   Gerhard Daniela S DS   Fraumeni Joseph F JF   Hoover Robert N RN   Chanock Stephen J SJ   Hunter David J DJ  

Nature genetics 20090329 5

We conducted a three-stage genome-wide association study (GWAS) of breast cancer in 9,770 cases and 10,799 controls in the Cancer Genetic Markers of Susceptibility (CGEMS) initiative. In stage 1, we genotyped 528,173 SNPs in 1,145 cases of invasive breast cancer and 1,142 controls. In stage 2, we analyzed 24,909 top SNPs in 4,547 cases and 4,434 controls. In stage 3, we investigated 21 loci in 4,078 cases and 5,223 controls. Two new loci achieved genome-wide significance. A pericentromeric SNP o  ...[more]

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