Dataset Information

Association of TM6SF2 rs58542926 T/C gene polymorphism with hepatocellular carcinoma: a meta-analysis.

ABSTRACT: BACKGROUND:Hepatocellular carcinoma (HCC) is the sixth-most common malignancy worldwide. Multiple previous studies have assessed the relationship between TM6SF2 gene polymorphism and the risk of developing HCC, with discrepant conclusions reached. To assess the association of TM6SF2 rs58542926 T/C gene polymorphism with liver cancer, we performed the current meta-analysis. METHODS:This study queried the MEDLINE, PubMed, EMBASE, and CENTRAL databases from inception to April 2019. Case-control studies assessing the relationship between TM6SF2 rs5854292 locus polymorphism and liver cancer were selected according to inclusion and exclusion criteria. The Stata 12.0 software was employed for data analysis. RESULTS:A total of 5 articles, encompassing 6873 patients, met inclusion criteria and were included in the meta-analysis. Statistical analysis showed that the TM6SF2 gene polymorphism was significantly associated with liver cancer in the allele contrast, dominant, recessive and over dominant models (T vs C, OR?=?1.621, 95%CI 1.379-1.905; CT?+?TT vs CC. OR?=?1.541, 95%CI 1.351-1.758; TT vs CT?+?CC, OR?=?2.897, 95%CI 1.690-4.966; CC?+?TT vs TC, OR?=?0.693, 95%CI 0.576-0.834). The Egger's test revealed no significant publication bias. CONCLUSION:The present findings suggest a significant association of TM6SF2 gene polymorphism with HCC risk in the entire population studied.

SUBMITTER: Tang S

PROVIDER: S-EPMC6868855 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Association of TM6SF2 rs58542926 T/C gene polymorphism with hepatocellular carcinoma: a meta-analysis.

Tang Shan S Zhang Jing J Mei Ting-Ting TT Guo Hai-Qing HQ Wei Xin-Huan XH Zhang Wen-Yan WY Liu Ya-Li YL Liang Shan S Fan Zuo-Peng ZP Ma Li-Xia LX Lin Wei W Liu Yi-Rong YR Qiu Li-Xia LX Yu Hai-Bin HB

BMC cancer 20191121 1

<h4>Background</h4>Hepatocellular carcinoma (HCC) is the sixth-most common malignancy worldwide. Multiple previous studies have assessed the relationship between TM6SF2 gene polymorphism and the risk of developing HCC, with discrepant conclusions reached. To assess the association of TM6SF2 rs58542926 T/C gene polymorphism with liver cancer, we performed the current meta-analysis.<h4>Methods</h4>This study queried the MEDLINE, PubMed, EMBASE, and CENTRAL databases from inception to April 2019. C ...[more]

PMID: 31752753

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Project description:Some studties reported that the polymorphism of TM6SF2 gene E167K affects the occurrence and the progression of hepatocytes carcinoma (hepatocellular, HCC). In oeder to investigate the effects of the polymorphism of TM6SF2 gene E167K in the pathogenesis of HCC, we explored its influence on the cell cycle in hepatocellular carcinoma cell HEPA1-6.HEPA 1-6 cells which could respectively overexpress TM6SF2 wild type and E167K variant were cultured and HEPA 1-6 cells with zero load plasmids were used as matched control. Flow cytometry was used to detect the cell cycles of these 3 type of HEPA 1-6 cells. Realtime fluores-cence quantitative PCR and western blot were used to analyzed the expression of regulatory factors (Cyclin D1?p53?P16?P27?P21 and Rb) of cell cycle. T-test was used in statistical analysis.Cell cycle phase distribution was presented by the proportion of cells in each phases (%). Compared with the control group, the cell cycle phase distribution (G1 phase 57.36 ± 0.21%, G2/M phase 25.61 ± 0.36%,S phases 19.31 ± 0.25%) had no differences in wild type group (G1 phase 57.63 ± 0.28%, G2/M phase 25.77 ± 0.51%, S phases 19.54 ± 0.25%; P < 0.05). Between variant type group and wild type group,G1 phase was significantly decreased (variant type group G1 phase 36.26 ± 0.31%, P < 0.05),S phase and G2/M phase were increased(variant type group S phase 28.41 ± 0.31%, P < 0.05;G2/M phase 35.23 ± 0.14%, P < 0.05), respectively. Compared with control group,the relative expression of CyclinD1?P53 and Rb mRNA in variant type group was significantly upregulated (2.03 ± 0.01 VS 1.04 ± 0.06, 1.88 ± 0.05 VS 1.37 ± 0.03, 1.29 ± 0.06 VS 1.15 ± 0.03, P < 0.05) and P27 mRNA in variant type group was significantly downregulated (0.56 ± 0.02 VS 0.85 ± 0.05, P < 0.05). Compared with wild type group, the relative expression of CyclinD1?P53 and Rb mRNA in variant type group was significantly upregulated (wild type group 1.00 ± 0.00, 1.48 ± 0.09, 1.18 ± 0.01, P < 0.05) and P27 mRNA in variant type group was significantly downregulated (variant type group 0.82 ± 0.05,P < 0.05). There was no statistical significance between wild type group and control group (P > 0.05). P16 and P21 expression showed no statistical sigtfificance in any of these three groups (P > 0.05).E167K polymorphism of TM6SF2 gene affects cell cycles of HEPA1-6 cells via up-regulating CyclinD1?P53 and Rb and down-regulating P27.

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.

Project description:BackgroundMethylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the metabolism of folate. The non-synonymous single nucleotide polymorphism (nsSNP), C677T (Ala>Val, rs1801133), has been verified to impair enzyme activity. The association with cancer susceptibility, including hepatocellular carcinoma (HCC), has also been widely studied. The results, however, were inconsistent. To shed light on the influence of MTHFR C677T polymorphism on HCC, a meta-analysis was conducted.MethodsThe meta-analysis of C677T consisted of 10 studies (1814 cases/2862 controls). The association was measured by using random-effect (RE) or fixed-effect (FE) odds ratio (OR) combined with 95% confidence intervals (CIs) according to the studies' heterogeneity.ResultsUsing genetic model analysis, C677T polymorphism was found to increase the risk of HCC in a complete overdominant model, which indicates that heterozygotes CT are at a lesser risk of HCC than either homozygotes CC or TT. Meta-analyses of the 10 studies showed that the TT genotype increased the risk of HCC as compared to the CT genotype: FE OR was 1.20 (95%CI: 1.00-1.45, p for heterogeneity = 0.21). When subgroup analysis was done between the HCC cases and the chronic liver disease (CLD) patients of four studies, meta-analysis showed that individuals with the TT genotype had increased HCC risk compared with those with the CT genotype: FE OR (TT vs. CT) reached 1.81 (1.22-2.71, p for heterogeneity = 0.25). Meanwhile, the C677T polymorphism also increased HCC risk in a recessive model when cases were compared to CLD patients of four studies: RE OR reached 1.85 (95%CI: 1.00-3.42, p for heterogeneity = 0.06). Overall, there was some extent heterogeneity when analyses were performed in various models. There was no publication bias.ConclusionMTHFR C677T polymorphism increased the risk of HCC in an overdominant model, and might be a risk factor for HCC occurrence, especially in CLD patients. The association warranted further studies.

Dataset Information

Association of TM6SF2 rs58542926 T/C gene polymorphism with hepatocellular carcinoma: a meta-analysis.

Publications

Association of TM6SF2 rs58542926 T/C gene polymorphism with hepatocellular carcinoma: a meta-analysis.

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