TY - JOUR
T1 - Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers
AU - Evans, Gareth
AU - Antoniou, Antonis C.
AU - Kuchenbaecker, Karoline B.
AU - Soucy, Penny
AU - Beesley, Jonathan
AU - Chen, Xiaoqing
AU - McGuffog, Lesley
AU - Lee, Andrew
AU - Barrowdale, Daniel
AU - Healey, Sue
AU - Sinilnikova, Olga M.
AU - Caligo, Maria A.
AU - Loman, Niklas
AU - Harbst, Katja
AU - Lindblom, Annika
AU - Arver, Brita
AU - Rosenquist, Richard
AU - Karlsson, Per
AU - Nathanson, Kate
AU - Domchek, Susan
AU - Rebbeck, Tim
N1 - C12292/A11174, Cancer Research UK, United KingdomC1287/A10118, Cancer Research UK, United KingdomC1287/A11990, Cancer Research UK, United KingdomC5047/A8385, Cancer Research UK, United KingdomCA- 06-503, NCI NIH HHS, United StatesCA116201, NCI NIH HHS, United StatesCA128978, NCI NIH HHS, United StatesP30-CA051008, NCI NIH HHS, United StatesP50 CA116201, NCI NIH HHS, United StatesR01 CA128978, NCI NIH HHS, United StatesR01 CA74415, NCI NIH HHS, United StatesRFA-CA-06-503, NCI NIH HHS, United StatesU01 CA69398, NCI NIH HHS, United StatesU01 CA69417, NCI NIH HHS, United StatesU01 CA69446, NCI NIH HHS, United StatesU01 CA69467, NCI NIH HHS, United StatesU01 CA69631, NCI NIH HHS, United StatesU01 CA69638, NCI NIH HHS, United States
PY - 2012/2/20
Y1 - 2012/2/20
N2 - 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.
AB - 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.
U2 - 10.1186/bcr3121
DO - 10.1186/bcr3121
M3 - Article
C2 - 22348646
SN - 1465-5411
VL - 14
JO - Breast Cancer Research
JF - Breast Cancer Research
IS - 1
M1 - R33
ER -
