Replication of breast cancer susceptibility loci in whites and African Americans using a Bayesian approach.
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.
["O'Brien|Katie M|KM|", 'Cole|Stephen R|SR|', 'Poole|Charles|C|', 'Bensen|Jeannette T|JT|', 'Herring|Amy H|AH|', 'Engel|Lawrence S|LS|', 'Millikan|Robert C|RC|']
D000328:Adult D001741:African Americans D000368:Aged D001499:Bayes Theorem D014408:Biomarkers, Tumor D001943:Breast Neoplasms D016022:Case-Control Studies D005260:Female D005819:Genetic Markers D055106:Genome-Wide Association Study D006801:Humans D016013:Likelihood Functions D016015:Logistic Models D008875:Middle Aged D009657:North Carolina D016017:Odds Ratio D020641:Polymorphism, Single Nucleotide D012042:Registries D012307:Risk Factors D044465:Whites
breast cancer genome-wide association studies genetics single nucleotide polymorphisms race Bayesian analysis GWAS replication