Dataset Information

DNMT3A -448A>G polymorphism and the risk for hepatocellular carcinoma.

ABSTRACT: DNA-methyltransferase (DNMT) 3A plays a significant role in carcinogenesis. Findings of a previous study suggested an association between the DNMT3A -448A>G single-nucleotide polymorphism (SNP) and susceptibility to gastric cancer (GC) and colorectal cancer (CRC). Hepatocellular carcinoma (HCC) is a common malignancy, with a similar expression pattern to GC. The aim of this case-control study was to determine whether there is an association between DNMT3A gene polymorphism and susceptibility to HCC. Real-time quantitive PCR (qPCR) was employed to detect DNMT3A expression in tumor and non-cancer liver tissue from 13 HCC patients. An increased expression of DNMT3A was detected, as well as -448A>G polymorphisms of DNMT3A promoter by polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP), confirmed by sequencing. The distribution of -448A>G polymorphisms was examined in 108 HCC patients and 225 healthy controls who were matched for age and gender. The association of -448A>G polymorphisms of DNMT3A and the risk of HCC was evaluated by stratified analysis according to the patient's age and gender. The allele frequency of -448A among HCC patients and the controls was 24.07 vs. 24.22%, respectively. The frequency of genotypes GG, AG, AA was 55.56 vs. 56.89%, 40.74 vs. 37.78%, 3.7 vs. 5.33%, respectively. The results indicated that -448A>G is not associated with susceptibility to HCC, although -448A>G is a functional single-nucleotide polymorphism (SNP) and increased the expression of DNMT3A in HCC cases. Findings of the present study suggested that the DNMT3A -448A>G polymorphism is an insufficient biomarker to predict the susceptibility to HCC.

SUBMITTER: Zhao C

PROVIDER: S-EPMC3917098 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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DNMT3A -448A>G polymorphism and the risk for hepatocellular carcinoma.

Zhao Chengcheng C Yan Feng F Wu Huazhang H Qiao Fengchang F Qiu Xuemei X Fan Hong H

Biomedical reports 20130530 4

DNA-methyltransferase (DNMT) 3A plays a significant role in carcinogenesis. Findings of a previous study suggested an association between the DNMT3A -448A>G single-nucleotide polymorphism (SNP) and susceptibility to gastric cancer (GC) and colorectal cancer (CRC). Hepatocellular carcinoma (HCC) is a common malignancy, with a similar expression pattern to GC. The aim of this case-control study was to determine whether there is an association between <i>DNMT3A</i> gene polymorphism and susceptibil ...[more]

PMID: 24649006

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Project description:Polymorphisms in pre-miRNAs may affect its expression, then having effect on its target mRNAs and be associated with cancer susceptibility. In the current study, we evaluated the association of a 3-base pair (3-bp) indel polymorphism (rs57408770) in pre-miR-3131 with hepatocellular carcinoma (HCC) susceptibility in a Chinese population. Logistic regression analysis showed that the insertion allele of rs57408770 was significantly associated with an increased risk for HCC occurrence in both case-control studies. To further investigated the molecular mechanism underlying the correlation between rs57408770 and the risk of HCC, overexpression of pre-miR-3131 in HCC cell line was performed. Human HCC cell lines Sk-Hep-1 was obtained from Shanghai Cell Bank of Chinese Academy of Sciences on 9 December 2013.The fragment of 366bp including the insert allele of rs57408770 in pre-miR-3131 was directly synthesized and cloned into BamHI and EcoRI sites of pEGFP-N1 yielding the wild-type vector (pEGFP-N1-miR3131-WT). The mutant-type vector (pEGFP-N1-miR3131-MT) including the delete allele of rs57408770 was generated using QuikChange Lightening Site-Directed Mutagenesis Kit. The resulting constructs were verified by direct sequencing. For overexpression experiments, cells were cultured in 6-well plates at a density of 200 000 cells per well the day before transfection. 2.5Î¼g plasmids of empty vector pEGFP-N1, pEGFP-N1-miR3131-WT or pEGFP-N1-miR3131-MT were transfected into the growing cells (about 80%-90% confluent) using Lipofectamine2000. After 24 hours of the transfection, the cells were collected for subsequent experiments.And human genome-wide gene expression profile assay was used to screen the targets of miR-3131. For overexpression experiments, cells were cultured in 6-well plates at a density of 200 000 cells per well the day before transfection. 2.5Î¼g plasmids of empty vector pEGFP-N1, pEGFP-N1-miR3131-WT or pEGFP-N1-miR3131-MT were transfected into the growing cells (about 80%-90% confluent) using Lipofectamine2000 (Invitrogen). After 24 hours of the transfection, the cells were collected for subsequent experiments. There are 3 samples in this experiment.

Project description:BackgroundCyclin D1 (CCND1) G870A polymorphism may be associated with hepatocellular carcinoma (HCC) risk, but the results of previous studies were inconsistent. Available evidence was meta-analyzed to assess their potential association.MethodsDatabases PubMed, EMBASE, Cochrane Library, Web of Science, Chinese Biomedical Literature database, China National Knowledge Infrastructure, and Google Scholar were systematically searched. Meta-analyses were performed to investigate the association of G870A polymorphism with HCC risk by calculating odds ratios (ORs) and 95% confidence intervals (CIs) from the data of relevant case-control studies.ResultsResults of this meta-analysis of six case-control studies involving 1,030 cases and 1,683 controls indicate that G870A polymorphism was not associated with HCC risk in any of the five genetic models tested (recessive model: AA vs GG + AG: OR =1.38, 95% CI =0.95-2.00, P=0.09; dominant model: AG + AA vs GG: OR =1.38, 95% CI =0.87-2.20, P=0.17; homozygous model: AA vs GG: OR =1.60, 95% CI =0.87-2.94, P=0.13; heterozygous model: AG vs GG: OR =1.24, 95% CI =0.86-1.79, P=0.25; allelic model: A vs G: OR =1.30, 95% CI =0.95-1.80, P=0.10). Subgroup analyses according to ethnicity showing marginally significant association between this single nucleotide polymorphism and HCC risk indicate that G870A may be significantly associated with HCC risk in Caucasian populations (recessive model: AA vs GG + AG: OR =2.34, 95% CI =1.60-3.42, P<0.0001; dominant model: AG + AA vs GG: OR =2.44, 95% CI =1.19-4.97, P=0.01; homozygous model: AA vs GG: OR =3.42, 95% CI =1.80-6.50, P=0.0002; allelic model: A vs G: OR =2.06, 95% CI =1.31-3.24, P=0.002), but not in Asian populations.ConclusionAvailable evidence suggests that no significant association between G870A polymorphism and HCC risk was found in either total populations or Asian populations. However, significant association was found in Caucasian populations. These results should be verified and extended in further detailed and well-designed studies involving larger, multiethnic samples.

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DNMT3A -448A>G polymorphism and the risk for hepatocellular carcinoma.

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DNMT3A -448A>G polymorphism and the risk for hepatocellular carcinoma.

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