A multistage genome-wide association study in breast cancer identifies two new risk alleles at 1p11.2 and 14q24.1 (RAD51L1).
A multistage genome-wide association study in breast cancer identifies two new risk alleles at 1p11.2 and 14q24.1 (RAD51L1).
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DOI：
10.1038/ng.353
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发表时间：
2009-05
期刊：
影响因子：
30.8
通讯作者：
Hunter, David J.
中科院分区：
文献类型：
--
作者：
Thomas, Gilles;Jacobs, Kevin B.;Kraft, Peter;Yeager, Meredith;Wacholder, Sholom;Cox, David G.;Hankinson, Susan E.;Hutchinson, Amy;Wang, Zhaoming;Yu, Kai;Chatterjee, Nilanjan;Garcia-Closas, Montserrat;Gonzalez-Bosquet, Jesus;Prokunina-Olsson, Ludmila;Orr, Nick;Willett, Walter C.;Colditz, Graham A.;Ziegler, Regina G.;Berg, Christine D.;Buys, Saundra S.;McCarty, Catherine A.;Feigelson, Heather Spencer;Calle, Eugenia E.;Thun, Michael J.;Diver, Ryan;Prentice, Ross;Jackson, Rebecca;Kooperberg, Charles;Chlebowski, Rowan;Lissowska, Jolanta;Peplonska, Beata;Brinton, Louise A.;Sigurdson, Alice;Doody, Michele;Bhatti, Parveen;Alexander, Bruce H.;Buring, Julie;Lee, I-Min;Vatten, Lars J.;Hveem, Kristian;Kumle, Merethe;Hayes, Richard B.;Tucker, Margaret;Gerhard, Daniela S.;Fraumeni, Joseph F., Jr.;Hoover, Robert N.;Chanock, Stephen J.;Hunter, David J.
癌症易感性遗传标志物（CGEMS）计划对9，770例乳腺癌病例和10，799例对照进行了三阶段全基因组关联研究（GWAS）。在第一阶段，我们对1,145例绝经后白色女性浸润性乳腺癌患者和1,142名对照者的528,173个单核苷酸多态性（SNP）进行了基因分型;在第二阶段，对4,547例患者和4,434名对照者的24,909个SNP进行了分析，这些SNP在第一阶段观察到的p值较低。在第3阶段，我们研究了4，078例病例和5，223例对照的21个基因座，其中第1阶段和第2阶段的p值较低。两个新的位点实现了全基因组意义。染色体1p11.2上的着丝粒周围SNP rs 11249433（p=6.74 × 10-10校正基因型检验，2个自由度）位于邻近NOTCH 2和FCGR 1B的连锁不平衡的大块中，并且主要与雌激素受体阳性乳腺癌相关。第二个SNP是染色体14q24.1上的rs 999737（p=1.74 × 10−7），定位于同源重组DNA修复途径中的基因RAD 51 L1，这是乳腺癌易感性的先前候选途径。我们证实了先前报道的染色体2 q35，5q11.2，5 p12，8 q24，10 q26和16q12.1上的标记。我们的研究结果强调了大规模复制在低突变率乳腺癌等位基因鉴定中的重要性。
The Cancer Genetic Markers of Susceptibility (CGEMS) initiative has conducted a three-stage genome-wide association study (GWAS) of breast cancer in 9,770 cases and 10,799 controls. In Stage 1, we genotyped 528,173 single nucleotide polymorphisms (SNPs) in 1,145 cases of invasive breast cancer among postmenopausal white women, and 1,142 controls; in Stage 2, 24,909 SNPs with low p values observed in Stage 1 were analyzed in 4,547 cases and 4,434 controls. In Stage 3 we investigated 21 loci in 4,078 cases and 5,223 controls with low p values from Stage 1 and 2 combined. Two novel loci achieved genome-wide significance. A pericentromeric SNP on chromosome 1p11.2, rs11249433, (p=6.74 × 10-10 adjusted genotype test with 2 degrees of freedom) resides in a large block of linkage disequilibrium neighboring NOTCH2 and FCGR1B and is predominantly associated with estrogen receptor-positive breast cancer. A second SNP, rs999737 on chromosome 14q24.1 (p=1.74 × 10−7), localizes to RAD51L1, a gene in the homologous recombination DNA repair pathway, a prior candidate pathway for breast cancer susceptibility. We confirmed previously reported markers on chromosome 2q35, 5q11.2, 5p12, 8q24, 10q26, and 16q12.1. Our results underscore the importance of large-scale replication in the identification of low penetrance breast cancer alleles.
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影响因子：
64.8
作者：
WOOSTER, R;BIGNELL, G;STRATTON, MR
通讯作者：
STRATTON, MR
影响因子：
3.7
作者：
Staiger, Harald;Machicao, Fausto;Kantartzis, Konstantinos;Schaefer, Silke A.;Kirchhoff, Kerstin;Guthoff, Martina;Silbernagel, Guenther;Stefan, Norbert;Fritsche, Andreas;Haering, Hans-Ulrich
通讯作者：
Haering, Hans-Ulrich
影响因子：
64.8
作者：
Erkko, Hannele;Xia, Bing;Winqvist, Robert
通讯作者：
Winqvist, Robert
影响因子：
30.8
作者：
Stacey, Simon N.;Manolescu, Andrei;Stefansson, Kari
通讯作者：
Stefansson, Kari
影响因子：
30.8
作者：
Skol, AD;Scott, LJ;Boehnke, M
通讯作者：
Boehnke, M