Putative linkage signals identified for breast cancer in African American families

Cancer Epidemiol Biomarkers Prev. 2015 Feb;24(2):442-7. doi: 10.1158/1055-9965.EPI-14-1131. Epub 2014 Dec 4.

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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • BRCA1 Protein / genetics
  • Black or African American / genetics*
  • Breast Neoplasms / genetics*
  • Chromosomes, Human, Pair 12 / genetics
  • Chromosomes, Human, Pair 17 / genetics
  • Chromosomes, Human, Pair 3 / genetics
  • Female
  • Genetic Linkage / genetics*
  • Genetic Predisposition to Disease / genetics*
  • Genome-Wide Association Study
  • Homeodomain Proteins / genetics
  • Humans
  • Middle Aged

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • HOXB13 protein, human
  • Homeodomain Proteins