Admixture mapping identifies a locus on 6q25 associated with breast cancer risk in US Latinas

• DOI: 10.1093/hmg/ddr617
• Publication Date: 2012-01-07T02:16:41Z
• Authors: Laura Fejerman; Gary K. Chen; Celeste Eng; Scott Huntsman; Donglei Hu; Amy Williams; Bogdan Pasaniuc; Esther M. John; Marc Via; Christopher Gignoux; Sue Ingles; Kristine R. Monroe; Laurence N. Kolonel; Gabriela Torres-M...; Eliseo J. Pérez-S...; Esteban González ...; Brian E. Henderson; Christopher A. Ha...; Elad Ziv
• Keywords: Genetic genealogy; Ancestry-informative marker; Genetic admixture; Genome-wide Association Study; Concordance; SNP; Genetic Association

Among US Latinas and Mexican women, those with higher European ancestry have increased risk of breast cancer. We combined an admixture mapping genome-wide association approach to search for genomic regions that may explain this observation. Latina women cancer (n= 1497) controls 1272) were genotyped using Affymetrix Illumina arrays. inferred locus-specific genetic compared the between cases controls. also performed single nucleotide polymorphism (SNP) analyses in interest. Correction multiple-hypothesis testing was conducted permutations (P(corrected)). identified one region where significantly associated risk: 6q25 [odds ratio (OR) per Indigenous American chromosome 0.75, 95% confidence interval (CI): 0.65-0.85, P= 1.1 × 10(-5), P(corrected)= 0.02]. A second on 11p15 showed a trend towards (OR 0.77, CI: 0.68-0.87, 4.3 0.08). In both regions, decreased concordance observations made global ancestry. The peak signal includes estrogen receptor 1 (ESR1) gene 5' region, locus previously implicated Genome-wide analysis found multi-SNP model explained regions. Our results confirm is partly due differences populations Americans origin. Fine-mapping within possibly loci will lead discovery biologically functional variant/s behind association.