Putative linkage signals identified for breast cancer in African American families

Abstract

Background: Genome-wide association studies have identified polymorphisms associated with breast cancer subtypes and across multiple population subgroups; however, few studies to date have applied linkage analysis to other population groups.

Methods: We performed the first genome-wide breast cancer linkage analysis in 106 African American families (comprising 179 affected and 79 unaffected members) not known to be segregating BRCA mutations to search for novel breast cancer loci. We performed regression-based model-free multipoint linkage analyses of the sibling pairs using SIBPAL, and two-level Haseman-Elston linkage analyses of affected relative pairs using RELPAL.

Results: We identified -log10 P values that exceed 4 on chromosomes 3q and 12q, as well as a region near BRCA1 on chromosome 17 (-log10 P values in the range of 3.0-3.2) using both sibling-based and relative-based methods; the latter observation may suggest that undetected BRCA1 mutations or other mutations nearby such as HOXB13 may be segregating in our sample.

Conclusions: In summary, these results suggest novel putative regions harboring risk alleles in African Americans that deserve further study.

Impact: We hope that our study will spur further family-based investigation into specific mechanisms for breast cancer disparities.

©2014 American Association for Cancer Research.

Figures

Figure 1

Selection of SNPs for linkage.

Figure 2

Genome-wide model-free multi-point linkage by SIBPAL, P-values based on up to 1,000,000 permutations (Haseman-Elston regression), without adjustment for any covariates.

Figure 3

Model-free multi-point linkage by RELPAL using all affected relative pairs and the IBD variance, adjusting for date of birth and global ancestry at the individual level. P-values evaluated on the basis of up to 1,000,000 permutations.