Abstract
Abstract Genome-wide association studies (GWAS) have identified approximately 107 common single nucleotide polymorphisms (index SNPs) for breast cancer risk. The target genes and underlying mechanisms for the large majority of the identified associations remain unknown. We conducted a cis-expression quantitative trait loci (cis-eQTL) analysis using transcriptome data from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) (N = 1,981), The Cancer Genome Atlas (TCGA) (N = 458), and the Genotype-Tissue Expression (GTEx) project (N = 183). We identified a total of 58 genes including SSBP4 at Benjamini-Hochberg adjusted P < 0.05 in at least one dataset and another gene, PAX9, at P < 0.05 with consistent association directions in all three datasets. Using data from the Encyclopedia of DNA Elements (ENCODE), we selected functional SNPs and showed that some alternative alleles could significantly change promoter activities of their target genes compared to reference alleles using luciferase reporter assays. The effects of target gene expression for those alleles were in line with eQTL observations. In addition, we validated the genes SETD9 and SSBP4 using Sequenom allelotype technique from 235 adjacent normal breast tissues and observed the allelic-specific expression associated with their index SNPs. This study revealed novel biological mechanisms for associations of genetic susceptibility risk loci for breast cancer. Citation Format: Xingyi Guo, Weiqiang Lin, Qiuyin Cai, Jiajun Shi, Yaqiong Sun, Xiao Pan, Mi-Ryung Han, Wanqing Wen, Bingshan Li, Jirong Long, Jianghua Chen, Wei Zheng. A comprehensive cis-eQTL analysis revealed target genes in breast cancer susceptibility loci identified in genome-wide association studies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1441. doi:10.1158/1538-7445.AM2017-1441
Published Version
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