Genome and transcriptome analysis highlights the association of rs2180341 variant with breast cancer

Abstract In 2008, a breast cancer genetic variant rs2180341 in 6q22.33 was first identified in Ashkenazi Jews population with P=2.90E-08. However, other studies reported controversial findings. Here, we conducted a three-stage analysis. In stage 1, we used the genome-wide association study datasets and candidate gene study datasets to evaluate the potential association between rs2180341 and breast cancer. In stage 2, we conducted an expression quantitative trait loci (eQTLs) analysis to further evaluate whether rs2180341 is associated with the expression of nearby genes. In stage 3, we evaluated the potential different expression of these nearby genes using case-control gene expression dataset. Our findings showed significant heterogeneity in all these selected genome-wide association study datasets and candidate gene study datasets. The breast cancer variant rs2180341 identified in Ashkenazi Jews population may not be directly replicated in other populations. Meanwhile, eQTLs analysis provides strong evidence implicating rs2180341 as a risk variant regulating the expression of nearby genes involved in kinds of cancers. However, few nearby genes showed significant different expression in breast cancer cases and controls.