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Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers

Antoniou, Antonis C.; Kartsonaki, Christiana; Sinilnikova, Olga M.; Soucy, Penny; McGuffog, Lesley; Healey, Sue; Lee, Andrew; Peterlongo, Paolo; Manoukian, Siranoush and Peissel, Bernard, et al. (2011) In Human Molecular Genetics 20(16). p.3304-3321
Abstract
Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs11249433 at 1p11.2 and rs999737 in RAD51L1 at 14q24.1. Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of... (More)
Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs11249433 at 1p11.2 and rs999737 in RAD51L1 at 14q24.1. Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of Investigators of Modifiers of BRCA1/2. In the analysis of 14 123 BRCA1 and 8053 BRCA2 mutation carriers of European ancestry, the 6q25.1 SNPs (r(2) = 0.14) were independently associated with the risk of breast cancer for BRCA1 mutation carriers [ hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.11-1.23, P-trend = 4.5 x 10(-9) for rs2046210; HR = 1.28, 95% CI: 1.18-1.40, P-trend = 1.3 x 10(-8) for rs9397435], but only rs9397435 was associated with the risk for BRCA2 carriers (HR = 1.14, 95% CI: 1.01-1.28, P-trend = 0.031). SNP rs11249433 (1p11.2) was associated with the risk of breast cancer for BRCA2 mutation carriers (HR = 1.09, 95% CI: 1.02-1.17, P-trend = 0.015), but was not associated with breast cancer risk for BRCA1 mutation carriers (HR = 0.97, 95% CI: 0.92-1.02, P-trend = 0.20). SNP rs999737 (RAD51L1) was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers (P-trend = 0.27 and 0.30, respectively). The identification of SNPs at 6q25.1 associated with breast cancer risk for BRCA1 mutation carriers will lead to a better understanding of the biology of tumour development in these women. (Less)
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Genetic Predisposition to Disease, Female, Pair 6, Pair 1, Human, Chromosomes, Breast Neoplasms, BRCA2 Protein, BRCA1 Protein, Alleles, Adult, Aged, Heterozygote, Humans, Middle Aged, Mutation, Polymorphism, Single Nucleotide, Risk Factors
in
Human Molecular Genetics
volume
20
issue
16
pages
3304 - 3321
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Oxford University Press
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  • wos:000293027100017
  • scopus:79960819760
ISSN
0964-6906
DOI
10.1093/hmg/ddr226
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English
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yes
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39d7324c-c993-4e43-8c53-4ed4938e0a3f (old id 2072146)
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http://dx.doi.org/10.1093/hmg/ddr226
http://www.ncbi.nlm.nih.gov/pubmed/21593217
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2011-09-02 08:30:56
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2017-06-11 03:09:20
@article{39d7324c-c993-4e43-8c53-4ed4938e0a3f,
  abstract     = {Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs11249433 at 1p11.2 and rs999737 in RAD51L1 at 14q24.1. Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of Investigators of Modifiers of BRCA1/2. In the analysis of 14 123 BRCA1 and 8053 BRCA2 mutation carriers of European ancestry, the 6q25.1 SNPs (r(2) = 0.14) were independently associated with the risk of breast cancer for BRCA1 mutation carriers [ hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.11-1.23, P-trend = 4.5 x 10(-9) for rs2046210; HR = 1.28, 95% CI: 1.18-1.40, P-trend = 1.3 x 10(-8) for rs9397435], but only rs9397435 was associated with the risk for BRCA2 carriers (HR = 1.14, 95% CI: 1.01-1.28, P-trend = 0.031). SNP rs11249433 (1p11.2) was associated with the risk of breast cancer for BRCA2 mutation carriers (HR = 1.09, 95% CI: 1.02-1.17, P-trend = 0.015), but was not associated with breast cancer risk for BRCA1 mutation carriers (HR = 0.97, 95% CI: 0.92-1.02, P-trend = 0.20). SNP rs999737 (RAD51L1) was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers (P-trend = 0.27 and 0.30, respectively). The identification of SNPs at 6q25.1 associated with breast cancer risk for BRCA1 mutation carriers will lead to a better understanding of the biology of tumour development in these women.},
  author       = {Antoniou, Antonis C. and Kartsonaki, Christiana and Sinilnikova, Olga M. and Soucy, Penny and McGuffog, Lesley and Healey, Sue and Lee, Andrew and Peterlongo, Paolo and Manoukian, Siranoush and Peissel, Bernard and Zaffaroni, Daniela and Cattaneo, Elisa and Barile, Monica and Pensotti, Valeria and Pasini, Barbara and Dolcetti, Riccardo and Giannini, Giuseppe and Putignano, Anna Laura and Varesco, Liliana and Radice, Paolo and Mai, Phuong L. and Greene, Mark H. and Andrulis, Irene L. and Glendon, Gord and Ozcelik, Hilmi and Thomassen, Mads and Gerdes, Anne-Marie and Kruse, Torben A. and Jensen, Uffe Birk and Crueger, Dorthe G. and Caligo, Maria A. and Laitman, Yael and Milgrom, Roni and Kaufman, Bella and Paluch-Shimon, Shani and Friedman, Eitan and Loman, Niklas and Harbst, Katja and Lindblom, Annika and Arver, Brita and Ehrencrona, Hans and Melin, Beatrice and Nathanson, Katherine L. and Domchek, Susan M. and Rebbeck, Timothy and Jakubowska, Ania and Lubinski, Jan and Gronwald, Jacek and Huzarski, Tomasz and Byrski, Tomasz and Cybulski, Cezary and Gorski, Bohdan and Osorio, Ana and Ramon y Cajal, Teresa and Fostira, Florentia and Andres, Raquel and Benitez, Javier and Hamann, Ute and Hogervorst, Frans B. and Rookus, Matti A. and Hooning, Maartje J. and Nelen, Marcel R. and van der Luijt, Rob B. and van Os, Theo A. M. and van Asperen, Christi J. and Devilee, Peter and Meijers-Heijboer, Hanne E. J. and Garcia, Encarna B. Gomez and Peock, Susan and Cook, Margaret and Frost, Debra and Platte, Radka and Leyland, Jean and Evans, D. Gareth and Lalloo, Fiona and Eeles, Ros and Izatt, Louise and Adlard, Julian and Davidson, Rosemarie and Eccles, Diana and Ong, Kai-ren and Cook, Jackie and Douglas, Fiona and Paterson, Joan and Kennedy, M. John and Miedzybrodzka, Zosia and Godwin, Andrew and Stoppa-Lyonnet, Dominique and Buecher, Bruno and Belotti, Muriel and Tirapo, Carole and Mazoyer, Sylvie and Barjhoux, Laure and Lasset, Christine and Leroux, Dominique and Faivre, Laurence and Bronner, Myriam and Prieur, Fabienne and Nogues, Catherine and Rouleau, Etienne and Pujol, Pascal and Coupier, Isabelle and Frenay, Marc and Hopper, John L. and Daly, Mary B. and Terry, Mary B. and John, Esther M. and Buys, Saundra S. and Yassin, Yosuf and Miron, Alexander and Goldgar, David and Singer, Christian F. and Tea, Muy-Kheng and Pfeiler, Georg and Dressler, Anne Catharina and Hansen, Thomas v. O. and Jonson, Lars and Ejlertsen, Bent and Barkardottir, Rosa Bjork and Kirchhoff, Tomas and Offit, Kenneth and Piedmonte, Marion and Rodriguez, Gustavo and Small, Laurie and Boggess, John and Blank, Stephanie and Basil, Jack and Azodi, Masoud and Toland, Amanda Ewart and Montagna, Marco and Tognazzo, Silvia and Agata, Simona and Imyanitov, Evgeny and Janavicius, Ramunas and Lazaro, Conxi and Blanco, Ignacio and Pharoah, Paul D. P. and Sucheston, Lara and Karlan, Beth Y. and Walsh, Christine S. and Olah, Edith and Bozsik, Aniko and Teo, Soo-Hwang and Seldon, Joyce L. and Beattie, Mary S. and van Rensburg, Elizabeth J. and Sluiter, Michelle D. and Diez, Orland and Schmutzler, Rita K. and Wappenschmidt, Barbara and Engel, Christoph and Meindl, Alfons and Ruehl, Ina and Varon-Mateeva, Raymonda and Kast, Karin and Deissler, Helmut and Niederacher, Dieter and Arnold, Norbert and Gadzicki, Dorothea and Schoenbuchner, Ines and Caldes, Trinidad and de la Hoya, Miguel and Nevanlinna, Heli and Aittomaki, Kristiina and Dumont, Martine and Chiquette, Jocelyne and Tischkowitz, Marc and Chen, Xiaoqing and Beesley, Jonathan and Spurdle, Amanda B. and Neuhausen, Susan L. and Ding, Yuan Chun and Fredericksen, Zachary and Wang, Xianshu and Pankratz, Vernon S. and Couch, Fergus and Simard, Jacques and Easton, Douglas F. and Chenevix-Trench, Georgia},
  issn         = {0964-6906},
  keyword      = {Genetic Predisposition to Disease,Female,Pair 6,Pair 1,Human,Chromosomes,Breast Neoplasms,BRCA2 Protein,BRCA1 Protein,Alleles,Adult,Aged,Heterozygote,Humans,Middle Aged,Mutation,Polymorphism,Single Nucleotide,Risk Factors},
  language     = {eng},
  number       = {16},
  pages        = {3304--3321},
  publisher    = {Oxford University Press},
  series       = {Human Molecular Genetics},
  title        = {Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers},
  url          = {http://dx.doi.org/10.1093/hmg/ddr226},
  volume       = {20},
  year         = {2011},
}