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Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers
Breast Cancer Res. 2012 ;14(1) :R33
PMID: 22348646    PMCID: PMCID:PMC3496151    URL: http://www.ncbi.nlm.nih.gov/pubmed/22348646
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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 x 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 x 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 x 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.
Notes
Antoniou, Antonis Cuno-Buecher-Curie-Net Bmc-Author-Email-Antoine-Depauw-Curie-Net Bmc-Author-Email-Sylvie-Mazoyer-Lyon-Unicancer-Fr Bmc-Author-Email-Carole-Verny-Lyon-Unicancer-Fr Bmc-Author-Email-Melanie-Leone-Lyon-Unicancer-Fr Bmc-Author-Email-Brigitte-Bressac-I Kuchenbaecker, Karoline Buno-Buecher-Curie-Net Bmc-Author-Email-Antoine-Depauw-Curie-Net Bmc-Author-Email-Sylvie-Mazoyer-Lyon-Unicancer-Fr Bmc-Author-Email-Carole-Verny-Lyon-Unicancer-Fr Bmc-Author-Email-Melanie-Leone-Lyon-Unicancer-Fr Bmc-Author-Email-Brigitte-Bressac- Soucy, Penny Beesley, Jonathan Chen, Xiaoqing McGuffog, Lesley Lee, Andrew Barrowdale, Daniel Healey, Sue Sinilnikova, Olga Muno-Buecher-Curie-Net Bmc-Author-Email-Antoine-Depauw-Curie-Net Bmc-Author-Email-Sylvie-Mazoyer-Lyon-Unicancer-Fr Bmc-Author-Email-Carole-Verny-Lyon-Unicancer-Fr Bmc-Author-Email-Melanie-Leone-Lyon-Unicancer-Fr Bmc-Author-Email-Brigitte-Bressac-Igr- Caligo, Maria Auno-Buecher-Curie-Net Bmc-Author-Email-Antoine-Depauw-Curie-Net 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Bmc-Author-Email-Melanie-Leone-Lyon-Unicancer-Fr Bmc-Author-Email-Brigitte-Bressac-Ig Chenevix-Trench, Georgia Couch, Fergus Juno-Buecher-Curie-Net Bmc-Author-Email-Antoine-Depauw-Curie-Net Bmc-Author-Email-Sylvie-Mazoyer-Lyon-Unicancer-Fr Bmc-Author-Email-Carole-Verny-Lyon-Unicancer-Fr Bmc-Author-Email-Melanie-Leone-Lyon-Unicancer-Fr Bmc-Author-Email-Brigitte-Bressac-Ig Simard, Jacques Easton, Douglas Funo-Buecher-Curie-Net Bmc-Author-Email-Antoine-Depauw-Curie-Net Bmc-Author-Email-Sylvie-Mazoyer-Lyon-Unicancer-Fr Bmc-Author-Email-Carole-Verny-Lyon-Unicancer-Fr Bmc-Author-Email-Melanie-Leone-Lyon-Unicancer-Fr Bmc-Author-Email-Brigitte-Bressac-I England Breast cancer research : BCR Breast Cancer Res. 2012 Feb 20;14(1):R33.