Journal Article

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

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-Mejía, Eliseo J. Pérez-Stable, Esteban González Burchard, Brian E. Henderson, Christopher A. Haiman and Elad Ziv

in Human Molecular Genetics

Volume 21, issue 8, pages 1907-1917
Published in print April 2012 | ISSN: 0964-6906
Published online January 2012 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddr617
Admixture mapping identifies a locus on 6q25 associated with breast cancer risk in US Latinas

Show Summary Details

Preview

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

Journal Article.  6590 words.  Illustrated.

Subjects: Genetics and Genomics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.