TY - JOUR
T1 - Associations of common variants at 1p11.2 and 14q24.1 (RAD51L1) with breast cancer risk and heterogeneity by tumor subtype
T2 - findings from the Breast Cancer Association Consortium
AU - Figueroa, Jonine D
AU - Garcia-Closas, Montserrat
AU - Humphreys, Manjeet
AU - Platte, Radka
AU - Hopper, John L
AU - Southey, Melissa C
AU - Apicella, Carmel
AU - Hammet, Fleur
AU - Schmidt, Marjanka K
AU - Broeks, Annegien
AU - Tollenaar, Rob A E M
AU - Van't Veer, Laura J
AU - Fasching, Peter A
AU - Beckmann, Matthias W
AU - Ekici, Arif B
AU - Strick, Reiner
AU - Peto, Julian
AU - dos Santos Silva, Isabel
AU - Fletcher, Olivia
AU - Johnson, Nichola
AU - Sawyer, Elinor
AU - Tomlinson, Ian
AU - Kerin, Michael
AU - Burwinkel, Barbara
AU - Marme, Federik
AU - Schneeweiss, Andreas
AU - Sohn, Christof
AU - Bojesen, Stig
AU - Flyger, Henrik
AU - Nordestgaard, Børge G
AU - Benítez, Javier
AU - Milne, Roger L
AU - Ignacio Arias, Jose
AU - Zamora, M Pilar
AU - Brenner, Hermann
AU - Müller, Heiko
AU - Arndt, Volker
AU - Rahman, Nazneen
AU - Turnbull, Clare
AU - Seal, Sheila
AU - Renwick, Anthony
AU - Brauch, Hiltrud
AU - Justenhoven, Christina
AU - Brüning, Thomas
AU - Chang-Claude, Jenny
AU - Hein, Rebecca
AU - Wang-Gohrke, Shan
AU - Dörk, Thilo
AU - Schürmann, Peter
AU - Bremer, Michael
AU - GENICA Network
PY - 2011
Y1 - 2011
N2 - A genome-wide association study (GWAS) identified single-nucleotide polymorphisms (SNPs) at 1p11.2 and 14q24.1 (RAD51L1) as breast cancer susceptibility loci. The initial GWAS suggested stronger effects for both loci for estrogen receptor (ER)-positive tumors. Using data from the Breast Cancer Association Consortium (BCAC), we sought to determine whether risks differ by ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), grade, node status, tumor size, and ductal or lobular morphology. We genotyped rs11249433 at 1p.11.2, and two highly correlated SNPs rs999737 and rs10483813 (r(2)= 0.98) at 14q24.1 (RAD51L1), for up to 46 036 invasive breast cancer cases and 46 930 controls from 39 studies. Analyses by tumor characteristics focused on subjects reporting to be white women of European ancestry and were based on 25 458 cases, of which 87% had ER data. The SNP at 1p11.2 showed significantly stronger associations with ER-positive tumors [per-allele odds ratio (OR) for ER-positive tumors was 1.13, 95% CI = 1.10-1.16 and, for ER-negative tumors, OR was 1.03, 95% CI = 0.98-1.07, case-only P-heterogeneity = 7.6 × 10(-5)]. The association with ER-positive tumors was stronger for tumors of lower grade (case-only P= 6.7 × 10(-3)) and lobular histology (case-only P= 0.01). SNPs at 14q24.1 were associated with risk for most tumor subtypes evaluated, including triple-negative breast cancers, which has not been described previously. Our results underscore the need for large pooling efforts with tumor pathology data to help refine risk estimates for SNP associations with susceptibility to different subtypes of breast cancer.
AB - A genome-wide association study (GWAS) identified single-nucleotide polymorphisms (SNPs) at 1p11.2 and 14q24.1 (RAD51L1) as breast cancer susceptibility loci. The initial GWAS suggested stronger effects for both loci for estrogen receptor (ER)-positive tumors. Using data from the Breast Cancer Association Consortium (BCAC), we sought to determine whether risks differ by ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), grade, node status, tumor size, and ductal or lobular morphology. We genotyped rs11249433 at 1p.11.2, and two highly correlated SNPs rs999737 and rs10483813 (r(2)= 0.98) at 14q24.1 (RAD51L1), for up to 46 036 invasive breast cancer cases and 46 930 controls from 39 studies. Analyses by tumor characteristics focused on subjects reporting to be white women of European ancestry and were based on 25 458 cases, of which 87% had ER data. The SNP at 1p11.2 showed significantly stronger associations with ER-positive tumors [per-allele odds ratio (OR) for ER-positive tumors was 1.13, 95% CI = 1.10-1.16 and, for ER-negative tumors, OR was 1.03, 95% CI = 0.98-1.07, case-only P-heterogeneity = 7.6 × 10(-5)]. The association with ER-positive tumors was stronger for tumors of lower grade (case-only P= 6.7 × 10(-3)) and lobular histology (case-only P= 0.01). SNPs at 14q24.1 were associated with risk for most tumor subtypes evaluated, including triple-negative breast cancers, which has not been described previously. Our results underscore the need for large pooling efforts with tumor pathology data to help refine risk estimates for SNP associations with susceptibility to different subtypes of breast cancer.
U2 - http://dx.doi.org/10.1093/hmg/ddr368
DO - http://dx.doi.org/10.1093/hmg/ddr368
M3 - Journal article
VL - 20
SP - 4693
EP - 4706
JO - Human Molecular Genetics
JF - Human Molecular Genetics
SN - 0964-6906
IS - 23
ER -