A novel variant on chromosome 6p21.1 is associated with the risk of developing colorectal cancer: a two-stage case-control study in Han Chinese.

ABSTRACT: Genes in inflammatory pathways play a pivotal role in the development of colorectal cancer. We conducted a two-stage case-control study and aimed at screening the colorectal cancer-associated genetic variations in inflammatory genes.Twenty-three candidate variants were genotyped in 952 primary colorectal cancer cases and 875 cancer-free controls from eastern China. Promising single nucleotide polymorphisms were further genotyped in 518 cases and 554 controls from middle China. Expression quantitative trait loci and differential gene expression analyses were performed for the associated gene.rs2282151 presented consistently significant associations with the risk of colorectal cancer in both stages (odds ratio (95 % confidence interval)?=?1.30 (1.16-1.46), risk allele?=?C, P combined?=?8.9E-6). Gene expression quantitative trait loci analyzes uncovered consistent cis-regulatory signals which showed that the C allele of rs2282151 was associated with increased expression level of heat shock protein 90 alpha family class B member 1 (HSP90AB1). Then we found that the mRNA expression levels of HSP90AB1 were significantly higher in tumor tissues than normal tissues (fold-change?=?1.83) in 28 pairs of colorectal tissue samples. The expression difference was consistent with data from online datasets. Additionally, we observed notable peaks of H3K27ac and H3K4me3 near the first intron of HSP90AB1 using ChIP-seq data from multiple cell lines (including HCT116).Our findings indicate that the C allele of the novel colorectal cancer-associated variant rs2282151 is associated with increased expression levels of HSP90AB1, which is expressed higher in colorectal tumor tissues than in normal tissues.

SUBMITTER: Xu C 

PROVIDER: S-EPMC5069896 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature