Dataset Information

Association between Single-Nucleotide Polymorphism in MicroRNA Target Site of DDB2 and Risk of Hepatocellular Carcinoma in a Southern Chinese Population.

ABSTRACT: Damage-specific DNA-binding protein 2 (DDB2) is a DNA repair protein mainly involved in nucleotide excision repair, which plays a pivotal role in maintaining genomic stability. In this study, we evaluated the association of single-nucleotide polymorphism (SNP) rs1050244 in miRNA target site of DDB2 gene with risk of hepatocellular carcinoma (HCC) among 1073 HCC patients and 1119 cancer-free controls in a southern Chinese population. Our results showed that no statistically significant association was found between DDB2 rs1050244 and HCC risk. In further analysis stratified by age, sex, smoking, alcohol drinking, and HBV infection status, we found that individuals carrying the CT/TT genotypes of SNP rs1050244 had a significantly decreased risk of HCC compared with those with the CC genotype among non-HBV infected population (adjusted OR?=?0.31, 95% CI?=?0.13-0.72), and a significant interaction was found between this SNP and HBV infection (P interaction=0.002). Our results suggested that the DDB2 rs1050244 C>T polymorphism was associated with the decreased risk of HCC among non-HBV infected population. Further studies with larger sample sizes are needed to validate our findings.

SUBMITTER: Qiu M

PROVIDER: S-EPMC7031712 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Association between Single-Nucleotide Polymorphism in MicroRNA Target Site of <i>DDB2</i> and Risk of Hepatocellular Carcinoma in a Southern Chinese Population.

Qiu Moqin M Liu Yingchun Y Zhou Zihan Z Jiang Yanji Y Lin Qiuling Q Huo Rongrui R Liang Xiumei X Yu Xiangyuan X Zhou Xianguo X Yu Hongping H

BioMed research international 20200208

Damage-specific DNA-binding protein 2 (DDB2) is a DNA repair protein mainly involved in nucleotide excision repair, which plays a pivotal role in maintaining genomic stability. In this study, we evaluated the association of single-nucleotide polymorphism (SNP) rs1050244 in miRNA target site of <i>DDB2</i> gene with risk of hepatocellular carcinoma (HCC) among 1073 HCC patients and 1119 cancer-free controls in a southern Chinese population. Our results showed that no statistically significant ass ...[more]

PMID: 32090112

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Project description:BACKGROUND: PTPN11, which encodes tyrosine phosphatase Shp2, is a critical gene mediating cellular responses to hormones and cytokines. Loss of Shp2 promotes hepatocellular carcinoma (HCC), suggesting that PTPN11 functions as a tumor suppressor in HCC tumorgenesis. The aim of this study was to evaluate the effects of the short tandem repeat (STR) polymorphism (rs199618935) within 3'UTR of PTPN11 on HCC susceptibility in Chinese populations. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed the associations in 400 patients from Jiangsu province of China, validating the findings in an additional 305 patients from Shanghai of China. Unconditional logistic regression was used to analyze the association between rs199618935 and HCC risk. Additional biochemical investigations and in-silico studies were used to evaluate the possible functional significance of this polymorphism. Logistic regression analysis showed that compared with individuals carrying shorter alleles (11 and 12 repeats), those subjects who carry longer alleles (13 and 14 repeats) had a significantly decreased risk of HCC [adjusted odds ratio (OR) = 0.63, 95% confidence interval (CI) ?= 0.53-0.76, P = 2.00 × 10(-7)], with the risk decreased even further in those carrying allele 15 and 16 (adjusted OR = 0.46, 95% CI = 0.34-0.62, P = 1.00 × 10(-7)). Biochemical investigations showed that longer alleles of rs199618935 conferred higher PTPN11 expression in vivo and in vitro. The altered luciferase activities in reporter gene system suggested that STR regulation of PTPN11 expression could be a transcriptional event. Finally, in-silico prediction revealed that different alleles of rs199618935 could alter the local structure of PTPN11 mRNA. CONCLUSIONS/SIGNIFICANCE: Taken together, our findings suggested that the STR polymorphism within PTPN11 contributes to hepatocarcinogenesis, possibly by affecting PTPN11 expression through a structure-dependent mechanism. The replication of our studies and further functional studies are needed to validate our findings.

Dataset Information

Association between Single-Nucleotide Polymorphism in MicroRNA Target Site of DDB2 and Risk of Hepatocellular Carcinoma in a Southern Chinese Population.

Publications

Association between Single-Nucleotide Polymorphism in MicroRNA Target Site of <i>DDB2</i> and Risk of Hepatocellular Carcinoma in a Southern Chinese Population.

Similar Datasets

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