Replication of breast cancer susceptibility loci in whites and African Americans using a Bayesian approach.

Published

Journal Article

Genome-wide association studies (GWAS) and candidate gene analyses have led to the discovery of several dozen genetic polymorphisms associated with breast cancer susceptibility, many of which are considered well-established risk factors for the disease. Despite attempts to replicate these same variant-disease associations in African Americans, the evaluable populations are often too small to produce precise or consistent results. We estimated the associations between 83 previously identified single nucleotide polymorphisms (SNPs) and breast cancer among Carolina Breast Cancer Study (1993-2001) participants using maximum likelihood, Bayesian, and hierarchical methods. The selected SNPs were previous GWAS hits (n = 22), near-hits (n = 19), otherwise well-established risk loci (n = 5), or located in the same genes as selected variants (n = 37). We successfully replicated 18 GWAS-identified SNPs in whites (n = 2,352) and 10 in African Americans (n = 1,447). SNPs in the fibroblast growth factor receptor 2 gene (FGFR2) and the TOC high mobility group box family member 3 gene (TOX3) were strongly associated with breast cancer in both races. SNPs in the mitochondrial ribosomal protein S30 gene (MRPS30), mitogen-activated protein kinase kinase kinase 1 gene (MAP3K1), zinc finger, MIZ-type containing 1 gene (ZMIZ1), and H19, imprinted maternally expressed transcript gene (H19) were associated with breast cancer in whites, and SNPs in the estrogen receptor 1 gene (ESR1) and H19 gene were associated with breast cancer in African Americans. We provide precise and well-informed race-stratified odds ratios for key breast cancer-related SNPs. Our results demonstrate the utility of Bayesian methods in genetic epidemiology and provide support for their application in small, etiologically driven investigations.

Full Text

Duke Authors

Cited Authors

  • O'Brien, KM; Cole, SR; Poole, C; Bensen, JT; Herring, AH; Engel, LS; Millikan, RC

Published Date

  • February 2014

Published In

Volume / Issue

  • 179 / 3

Start / End Page

  • 382 - 394

PubMed ID

  • 24218030

Pubmed Central ID

  • 24218030

Electronic International Standard Serial Number (EISSN)

  • 1476-6256

International Standard Serial Number (ISSN)

  • 0002-9262

Digital Object Identifier (DOI)

  • 10.1093/aje/kwt258

Language

  • eng