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Comparative Study
. 2011 Oct;130(4):529-37.
doi: 10.1007/s00439-011-0973-1. Epub 2011 Mar 19.

Potential Novel Candidate Polymorphisms Identified in Genome-Wide Association Study for Breast Cancer Susceptibility

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Free PMC article
Comparative Study

Potential Novel Candidate Polymorphisms Identified in Genome-Wide Association Study for Breast Cancer Susceptibility

Badan Sehrawat et al. Hum Genet. .
Free PMC article

Abstract

Previous genome-wide association studies (GWAS) have shown several risk alleles to be associated with breast cancer. However, the variants identified so far contribute to only a small proportion of disease risk. The objective of our GWAS was to identify additional novel breast cancer susceptibility variants and to replicate these findings in an independent cohort. We performed a two-stage association study in a cohort of 3,064 women from Alberta, Canada. In Stage I, we interrogated 906,600 single nucleotide polymorphisms (SNPs) on Affymetrix SNP 6.0 arrays using 348 breast cancer cases and 348 controls. We used single-locus association tests to determine statistical significance for the observed differences in allele frequencies between cases and controls. In Stage II, we attempted to replicate 35 significant markers identified in Stage I in an independent study of 1,153 cases and 1,215 controls. Genotyping of Stage II samples was done using Sequenom Mass-ARRAY iPlex platform. Six loci from four different gene regions (chromosomes 4, 5, 16 and 19) showed statistically significant differences between cases and controls in both Stage I and Stage II testing, and also in joint analysis. The identified variants were from EDNRA, ROPN1L, C16orf61 and ZNF577 gene regions. The presented joint analyses from the two-stage study design were not significant after genome-wide correction. The SNPs identified in this study may serve as potential candidate loci for breast cancer risk in a further replication study in Stage III from Alberta population or independent validation in Caucasian cohorts elsewhere.

Figures

Fig. 1
Fig. 1
Manhattan plot for Stage I association study showing 35,589 markers (p < 0.05) distributed across chromosomes. This graph is plotted against allelic χ2p values on –log10 scale to indicate polygenic nature of breast cancer susceptibility

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