A multi-stage genome-wide association in breast cancer identifies two novel risk alleles at 1p11.2 and 14q24.1 (RAD51L1)
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...
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| Veröffentlicht in: | Nature genetics 2009-03, Vol.41 (5), p.579-584 |
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| creator | 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. Hoover, Robert N. Chanock, Stephen J Hunter, David J. |
| description | 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. |
| doi_str_mv | 10.1038/ng.353 |
| format | Article |
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-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.</description><identifier>ISSN: 1061-4036</identifier><identifier>EISSN: 1546-1718</identifier><identifier>DOI: 10.1038/ng.353</identifier><identifier>PMID: 19330030</identifier><language>eng</language><ispartof>Nature genetics, 2009-03, Vol.41 (5), p.579-584</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids></links><search><creatorcontrib>Thomas, Gilles</creatorcontrib><creatorcontrib>Jacobs, Kevin B.</creatorcontrib><creatorcontrib>Kraft, Peter</creatorcontrib><creatorcontrib>Yeager, Meredith</creatorcontrib><creatorcontrib>Wacholder, Sholom</creatorcontrib><creatorcontrib>Cox, David G.</creatorcontrib><creatorcontrib>Hankinson, Susan E.</creatorcontrib><creatorcontrib>Hutchinson, Amy</creatorcontrib><creatorcontrib>Wang, Zhaoming</creatorcontrib><creatorcontrib>Yu, Kai</creatorcontrib><creatorcontrib>Chatterjee, Nilanjan</creatorcontrib><creatorcontrib>Garcia-Closas, Montserrat</creatorcontrib><creatorcontrib>Gonzalez-Bosquet, Jesus</creatorcontrib><creatorcontrib>Prokunina-Olsson, Ludmila</creatorcontrib><creatorcontrib>Orr, Nick</creatorcontrib><creatorcontrib>Willett, Walter C.</creatorcontrib><creatorcontrib>Colditz, Graham A.</creatorcontrib><creatorcontrib>Ziegler, Regina G.</creatorcontrib><creatorcontrib>Berg, Christine D.</creatorcontrib><creatorcontrib>Buys, Saundra S.</creatorcontrib><creatorcontrib>McCarty, Catherine A.</creatorcontrib><creatorcontrib>Feigelson, Heather Spencer</creatorcontrib><creatorcontrib>Calle, Eugenia E.</creatorcontrib><creatorcontrib>Thun, Michael J.</creatorcontrib><creatorcontrib>Diver, Ryan</creatorcontrib><creatorcontrib>Prentice, Ross</creatorcontrib><creatorcontrib>Jackson, Rebecca</creatorcontrib><creatorcontrib>Kooperberg, Charles</creatorcontrib><creatorcontrib>Chlebowski, Rowan</creatorcontrib><creatorcontrib>Lissowska, Jolanta</creatorcontrib><creatorcontrib>Peplonska, Beata</creatorcontrib><creatorcontrib>Brinton, Louise A.</creatorcontrib><creatorcontrib>Sigurdson, Alice</creatorcontrib><creatorcontrib>Doody, Michele</creatorcontrib><creatorcontrib>Bhatti, Parveen</creatorcontrib><creatorcontrib>Alexander, Bruce H.</creatorcontrib><creatorcontrib>Buring, Julie</creatorcontrib><creatorcontrib>Lee, I-Min</creatorcontrib><creatorcontrib>Vatten, Lars J</creatorcontrib><creatorcontrib>Hveem, Kristian</creatorcontrib><creatorcontrib>Kumle, Merethe</creatorcontrib><creatorcontrib>Hayes, Richard B.</creatorcontrib><creatorcontrib>Tucker, Margaret</creatorcontrib><creatorcontrib>Gerhard, Daniela S.</creatorcontrib><creatorcontrib>Fraumeni, Joseph F.</creatorcontrib><creatorcontrib>Hoover, Robert N.</creatorcontrib><creatorcontrib>Chanock, Stephen J</creatorcontrib><creatorcontrib>Hunter, David J.</creatorcontrib><title>A multi-stage genome-wide association in breast cancer identifies two novel risk alleles at 1p11.2 and 14q24.1 (RAD51L1)</title><title>Nature genetics</title><description>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. 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genetics</jtitle><date>2009-03-29</date><risdate>2009</risdate><volume>41</volume><issue>5</issue><spage>579</spage><epage>584</epage><pages>579-584</pages><issn>1061-4036</issn><eissn>1546-1718</eissn><abstract>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.</abstract><pmid>19330030</pmid><doi>10.1038/ng.353</doi></addata></record> |
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| source | Nature; SpringerLink Journals - AutoHoldings |
| title | A multi-stage genome-wide association in breast cancer identifies two novel risk alleles at 1p11.2 and 14q24.1 (RAD51L1) |
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