DUSP10 gene polymorphism and risk of colorectal cancer in the Han Chinese population

Abstract

Dual-specificity protein phosphatases (DUSP) negatively regulate members of the mitogen-activated protein kinase superfamily, which is associated with cellular proliferation and differentiation. A recent study suggests that DUSP10 is frequently upregulated in colorectal cancer (CRC). Our study aimed to assess whether DUSP10 contributes to the risk of CRC. We analyzed nine tag single nucleotide polymorphisms (tSNPs) of DUSP10 in a case-control study of Han Chinese by the χ²-test and the SHEsis software. We found that two tSNPs (rs908858, P=0.00004; rs11118838, P=0.02510) were significantly associated with CRC using the χ²-test. Using the SHEsis software, six tSNPs (rs12041033, rs17010629, rs12724393, rs12036163, rs11118838, rs12044821) were found in the same linkage disequilibrium block. Within this linkage disequilibrium block, haplotype 'CTCAAC' showed an increased risk of CRC by 42%. By global haplotype analysis, we found that the haplotype 'ACTCAACTA' may increase the risk of CRC by ∼53%; the haplotype 'GCCCACCCA' may decrease the risk by ∼46%. Our results, combined with previous studies, suggest that certain mutations in DUSP10 correlate with the incidence of CRC. Thus, the function of the DUSP10 gene product may contribute toward CRC in the Han Chinese population.

Association between polymorphisms of MIR17HG and risk of colorectal cancer in the Chinese Han population

“…The single nucleotide polymorphism (SNP) is the most common form of human genetic variations and are significantly associated with many cancers risk (Geng et al, ; Hu et al, ; Tian et al, ). Recently, an increasing number of evidence suggests that genetic susceptibility plays an important role in the occurrence of colorectal cancer (Duan et al, ; Su et al, ; Wang et al, ; Zhang, Li, Du, et al, ).…”

<p>Variants of <em>MIR137HG</em> Genes are Associated with Liver Cancer Risk in Chinese Li Population</p>

“…SPSS software package (version 20.0; SPSS Inc., Chicago, IL, USA) was adopted to process data, and P < 0.05 was regarded as statistically significant. 12,13 Hardy-Weinberg equilibrium (HWE) P values obtained from exact tests 14 were used to evaluate whether the control group meets HWE. The distributions of genotype and allele frequencies between cases and controls were compared by χ 2 tests.…”

The Dual-Specificity Phosphatase 10 (DUSP10): Its Role in Cancer, Inflammation, and Immunity

“…A negative feedback loop in the regulation of DUSP10 by miRNAs, may exist, since miR-21 and miR-155 transcription is dependent of AP-1 activity, a transcription factor downregulated by DUSP10 expression [30]. In hepatocellular cancer and pancreatic cancer, miR-181 and miR92a, respectively, negatively regulate the DUSP10 expression, affecting the proliferation and migration of tumorigenic cells [31,32]. Enhanced mir-92a expression is also detected at the peak of the EAE and downregulates DUSP10 transcription [33].…”

“…DUSP10 mRNA is frequently over-expressed in colon carcinoma and different polymorphisms (SNPs) have been identified near or within the sequence of DUSP10 gene, which are correlated with colorectal cancer (CRC) risk. In a Chinese population, two SNPs (rs908858 and rs11118838) lead to the haplotypes ‘ACTCAACTA’ or ‘GCCCACCCA’, which correlate with an increased or a decreased CRC risk, respectively [31]. These polymorphisms and SNP rs12724393 are associated with less CRC risk in females of Chinese population; while only the rs908858 is linked with a decreased risk in males [32].…”