Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers Journal Article

   

Authors:	Antoniou, A. C.; Kuchenbaecker, K. B.; Soucy, P.; Beesley, J.; Chen, X.; McGuffog, L.; Lee, A.; Barrowdale, D.; Healey, S.; Sinilnikova, O. M.; Caligo, M. A.; Loman, N.; Harbst, K.; Lindblom, A.; Arver, B.; Rosenquist, R.; Karlsson, P.; Nathanson, K.; Domchek, S.; Rebbeck, T.; Joseph, V.; Dutra Clarke, A.; Offit, K.
Article Title:	Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers
Abstract:	Introduction: Several common alleles have been shown to be associated with breast and/or ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Recent genome-wide association studies of breast cancer have identified eight additional breast cancer susceptibility loci: rs1011970 (9p21, CDKN2A/B), rs10995190 (ZNF365), rs704010 (ZMIZ1), rs2380205 (10p15), rs614367 (11q13), rs1292011 (12q24), rs10771399 (12p11 near PTHLH) and rs865686 (9q31.2).Methods: To evaluate whether these single nucleotide polymorphisms (SNPs) are associated with breast cancer risk for BRCA1 and BRCA2 carriers, we genotyped these SNPs in 12,599 BRCA1 and 7,132 BRCA2 mutation carriers and analysed the associations with breast cancer risk within a retrospective likelihood framework.Results: Only SNP rs10771399 near PTHLH was associated with breast cancer risk for BRCA1 mutation carriers (per-allele hazard ratio (HR) = 0.87, 95% CI: 0.81 to 0.94, P-trend = 3 × 10 -4). The association was restricted to mutations proven or predicted to lead to absence of protein expression (HR = 0.82, 95% CI: 0.74 to 0.90, P-trend = 3.1 × 10 -5, P-difference = 0.03). Four SNPs were associated with the risk of breast cancer for BRCA2 mutation carriers: rs10995190, P-trend = 0.015; rs1011970, P-trend = 0.048; rs865686, 2df-P = 0.007; rs1292011 2df-P = 0.03. rs10771399 (PTHLH) was predominantly associated with estrogen receptor (ER)-negative breast cancer for BRCA1 mutation carriers (HR = 0.81, 95% CI: 0.74 to 0.90, P-trend = 4 × 10 -5) and there was marginal evidence of association with ER-negative breast cancer for BRCA2 mutation carriers (HR = 0.78, 95% CI: 0.62 to 1.00, P-trend = 0.049).Conclusions: The present findings, in combination with previously identified modifiers of risk, will ultimately lead to more accurate risk prediction and an improved understanding of the disease etiology in BRCA1 and BRCA2 mutation carriers. © 2012 Antoniou et al.; licensee BioMed Central Ltd.
Keywords:	adult; protein expression; aged; unclassified drug; gene mutation; single nucleotide polymorphism; cancer risk; allele; disease association; breast cancer; protein; chromosome 9p; gene locus; genetic variability; genotype; brca1 protein; brca2 protein; cyclin dependent kinase inhibitor 2a; estrogen receptor; chromosome 12q; chromosome 11q; chromosome 12p; chromosome 9q; cyclin dependent kinase inhibitor 2b; pthlh protein; zmiz1 protein; znf365 protein; chromosome 10p
Journal Title:	Breast Cancer Research
Volume:	14
Issue:	1
ISSN:	1465-5411
Publisher:	Biomed Central Ltd
Date Published:	2012-01-01
Start Page:	R33
Language:	English
DOI:	10.1186/bcr3121
PROVIDER:	scopus
PMCID:	PMC3496151
PUBMED:	22348646
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84862821318&partnerID=40&md5=839300595227b6de7dcb1b22fa782ff9
Notes:	--- - "Cited By (since 1996): 3" - "Export Date: 28 January 2013" - "CODEN: BCRRC" - "Source: Scopus"

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