Replication and Functional Genomic Analyses of the Breast Cancer Susceptibility Locus at 6q25.1 Generalize Its Importance in Women of Chinese, Japanese, and European Ancestry
- 14 February 2011
- journal article
- research article
- Published by American Association for Cancer Research (AACR) in Cancer Research
- Vol. 71 (4), 1344-1355
- https://doi.org/10.1158/0008-5472.can-10-2733
Abstract
We evaluated the generalizability of a single nucleotide polymorphism (SNP), rs2046210 (A/G allele), associated with breast cancer risk that was initially identified at 6q25.1 in a genome-wide association study conducted among Chinese women. In a pooled analysis of more than 31,000 women of East-Asian, European, and African ancestry, we found a positive association for rs2046210 and breast cancer risk in Chinese women [ORs (95% CI) = 1.30 (1.22–1.38) and 1.64 (1.50–1.80) for the AG and AA genotypes, respectively, P for trend = 1.54 × 10−30], Japanese women [ORs (95% CI) = 1.31 (1.13–1.52) and 1.37 (1.06–1.76), P for trend = 2.51 × 10−4], and European-ancestry American women [ORs (95% CI) = 1.07 (0.99–1.16) and 1.18 (1.04–1.34), P for trend = 0.0069]. No association with this SNP, however, was observed in African American women [ORs (95% CI) = 0.81 (0.63–1.06) and 0.85 (0.65–1.11) for the AG and AA genotypes, respectively, P for trend = 0.4027]. In vitro functional genomic studies identified a putative functional variant, rs6913578. This SNP is 1,440 bp downstream of rs2046210 and is in high linkage disequilibrium with rs2046210 in Chinese (r2 = 0.91) and European-ancestry (r2 = 0.83) populations, but not in Africans (r2 = 0.57). SNP rs6913578 was found to be associated with breast cancer risk in Chinese and European-ancestry American women. After adjusting for rs2046210, the association of rs6913578 with breast cancer risk in African Americans approached borderline significance. Results from this large consortium study confirmed the association of rs2046210 with breast cancer risk among women of Chinese, Japanese, and European ancestry. This association may be explained in part by a putatively functional variant (rs6913578) identified in the region. Cancer Res; 71(4); 1344–55. ©2011 AACR.Keywords
Other Versions
This publication has 28 references indexed in Scilit:
- Evaluation of Breast Cancer Susceptibility Loci in Chinese WomenCancer Epidemiology, Biomarkers & Prevention, 2010
- Ancestry-Shift Refinement Mapping of the C6orf97-ESR1 Breast Cancer Susceptibility LocusPLoS Genetics, 2010
- Genetic and Clinical Predictors for Breast Cancer Risk Assessment and Stratification Among Chinese WomenJNCI Journal of the National Cancer Institute, 2010
- Genome-wide association study identifies five new breast cancer susceptibility lociNature Genetics, 2010
- Evaluation of 11 Breast Cancer Susceptibility Loci in African-American WomenCancer Epidemiology, Biomarkers & Prevention, 2009
- Newly discovered breast cancer susceptibility loci on 3p24 and 17q23.2Nature Genetics, 2009
- Genome-wide association study identifies a new breast cancer susceptibility locus at 6q25.1Nature Genetics, 2009
- Screening and association testing of common coding variation in steroid hormone receptor co-activator and co-repressor genes in relation to breast cancer risk: the Multiethnic CohortBMC Cancer, 2009
- Functional polymorphisms in the BRCA1 promoter influence transcription and are associated with decreased risk for breast cancer in Chinese womenJournal of Medical Genetics, 2008
- Genome-wide association study identifies novel breast cancer susceptibility lociNature, 2007