Abstract
BackgroundGenes 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.MethodsTwenty-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.Resultsrs2282151 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).ConclusionsOur 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2843-7) contains supplementary material, which is available to authorized users.
Highlights
Genes in inflammatory pathways play a pivotal role in the development of colorectal cancer
We mainly focused on the polymorphism of the candidate genes including NFKBIA, NFKBIB, NFKBIE, IL6, STAT3, and CXCL12
Associations of candidate tagSNPs with Colorectal cancer (CRC) All the 23 candidate Single nucleotide polymorphism (SNP) in this study population were consistent with HWE (P > 0.05) in the controls in both stages
Summary
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. Previous studies have shown that inflammatory processes played an important role in the etiology of cancers including CRC [3,4,5,6]. Several genes in the inflammatory pathway have been identified to be linked to colorectal cancer, including NFKBIA, NFKBIB, NFKBIE, IL6, STAT3, CXCL12, COX2, and PPARG etc. Associations between the IL6 gene polymorphisms and CRC have been observed by previous studies [19,20,21,22]. We mainly focused on the polymorphism of the candidate genes including NFKBIA, NFKBIB, NFKBIE, IL6, STAT3, and CXCL12
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