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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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keywords
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
publisher
Oxford University Press
external identifiers
  • wos:000293027100017
  • scopus:79960819760
  • pmid:21593217
ISSN
0964-6906
DOI
10.1093/hmg/ddr226
language
English
LU publication?
yes
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39d7324c-c993-4e43-8c53-4ed4938e0a3f (old id 2072146)
alternative location
http://dx.doi.org/10.1093/hmg/ddr226
http://www.ncbi.nlm.nih.gov/pubmed/21593217
date added to LUP
2016-04-01 10:20:30
date last changed
2026-08-13 08:35:02
@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}},
  issn         = {{0964-6906}},
  keywords     = {{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}},
  doi          = {{10.1093/hmg/ddr226}},
  volume       = {{20}},
  year         = {{2011}},
}