Genetic risk of hepatocellular carcinoma in patients with hepatitis C virus: A case control study
Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama city, Japan. Journal of Gastroenterology and Hepatology
(Impact Factor: 3.5).
10/2011; 27(4):797-804. DOI: 10.1111/j.1440-1746.2011.06948.x
BACKGROUD AND AIM: Chronic hepatitis C virus (HCV) infection is a well known risk factor for hepatocellular carcinoma (HCC). The aim of this study is to elucidate the genetic risk of development and recurrence of HCC in patients with HCV.
A total of 468 patients with HCV, including 265 with HCC were enrolled. We genotyped 88 single nucleotide polymorphisms (SNPs) in 81 genes expected to influence hepatocarcinogenesis using the iPLEX assay. Risk of HCC was clarified by stratifying patients into risk groups based on the multiplied odds ratio (MOR) for SNPs associated with HCC, and the cumulative effects on the development and recurrence of HCC were analyzed.
Six SNPs associated with risk of HCC were identified (OR range: 0.29-1.76). These included novel SNPs for hepatocarcinogenesis with HCV CCND2 rs1049606, RAD23B rs1805329, CEP164 rs573455, and GRP78rs430397 in addition to the known SNPs MDM2 rs2279744 and ALDH2 rs671. MOR analysis revealed that the highest risk group exerted about a 19-fold higher relative OR compared with the lowest risk group (P = 1.08 × 10(-5)). Predicted 10-year HCC risk ranged from 1.7% to 96% depending on the risk group and the extent of fibrosis. Recurrence-free survival of radiofrequency ablation-treated HCC in the high risk group (n = 53) was lower than that of low risk group (n = 58, P = 0.038).
Single nucleotide polymorphisms of CCND2, RAD23B, GRP78, CEP164, MDM2, and ALDH2 genes were significantly associated with development and recurrence of HCC in Japanese patients with HCV.
Figures in this publication
Available from: Mei Liu
- "The role of MDM2 in HCC and its overexpression in HCC patients are studied by many researchers. A study on Japanese patients with HCV infection showed that MDM2 gene was significantly associated with development and recurrence of HCC . MDM2 SNP309 plays a major role in the carcinogenesis of HCC, especially among Caucasian populations . "
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ABSTRACT: Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide. Although new therapeutic strategies have been continuously developed and applied to clinical treatment for HCC, the prognosis is still very poor. Thus, early detection of HCC may enhance effective and curative management. In this study, autoantibody responses to MDM2 protein in HCC patient's serum were evaluated by enzyme-linked immunosorbent assay (ELISA) and part sera were evaluated by Western blotting and indirect immunofluorescence assay. Immunohistochemistry (IHC) over tissue array slides was also performed to analyze protein expression of MDM2 in HCC and control tissues. The prevalence of autoantibodies against MDM2 was significantly higher than that in liver cirrhosis (LC), chronic hepatitis (CH), and normal human sera (NHS). The average titer of autoantibodies against MDM2 in HCC serum was higher compared to that in LC, CH, and NHS. A high titer of autoantibodies against MDM2 in ELISA could be observed in the serum in 6 to 9 months before the clinical diagnosis of HCC in the serum of several HCC patients with serial bleeding samples. Our preliminary data indicate that MDM2 and anti-MDM2 system may be a potential biomarker for early stage HCC screening and immunodiagnosis.
Research Journal of Immunology 05/2014; 2014:906532. DOI:10.1155/2014/906532
Available from: Shan Li
- "Over the last two decades, a number of case–control studies have been conducted to investigate the associations between TP53 R72P and MDM2 SNP309 polymorphisms and HCC risk, but the results remain controversial and inconclusive. With respect to MDM2 SNP309 polymorphism, a meta-analysis by Ma et al.  found that the MDM2 SNP309 polymorphism was associated with an increased HCC risk in Asians and Caucasians, however, they failed to include all eligible studies in the meta-analysis , , , which make their conclusions questionable. With respect to TP53 R72P polymorphism, two meta-analyses ,  investigating the same hypothesis, quite similar in methods and performed almost at the same time, yielded different conclusions. "
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ABSTRACT: The association between TP53 R72P and/or MDM2 SNP309 polymorphisms and hepatocellular carcinoma (HCC) risk has been widely reported, but results were inconsistent. To clarify the effects of these polymorphisms on HCC risk, an updated meta-analysis of all available studies was conducted.
Eligible articles were identified by search of databases including PubMed, Cochrane Library, EMBASE and Chinese Biomedical Literature database (CBM) for the period up to July 2013. Data were extracted by two independent authors and pooled odds ratio (OR) with 95% confidence interval (CI) was calculated. Metaregression and subgroup analyses were performed to identify the source of heterogeneity.
Finally, a total of 10 studies including 2,243 cases and 3,615 controls were available for MDM2 SNP309 polymorphism and 14 studies containing 4,855 cases and 6,630 controls were included for TP53 R72P polymorphism. With respect to MDM2 SNP309 polymorphism, significantly increased HCC risk was found in the overall population. In subgroup analysis by ethnicity and hepatitis virus infection status, significantly increased HCC risk was found in Asians, Caucasians, Africans, and HCV positive patients. With respect to TP53 R72P polymorphism, no significant association with HCC risk was observed in the overall and subgroup analyses. In the MDM2 SNP309-TP53 R72P interaction analysis, we found that subjects with MDM2 309TT and TP53 Pro/Pro genotype, MDM2 309 TG and TP53 Arg/Pro genotype, and MDM2 309 GG and TP53 Pro/Pro genotype were associated with significantly increased risk of developing HCC as compared with the reference MDM2 309TT and TP53 Arg/Arg genotype.
We concluded that MDM2 SNP309 polymorphism may play an important role in the carcinogenesis of HCC. In addition, our findings further suggest that the combination of MDM2 SNP 309 and TP53 Arg72Pro genotypes confers higher risk to develop HCC. Further large and well-designed studies are needed to confirm this association.
PLoS ONE 12/2013; 8(12):e82773. DOI:10.1371/journal.pone.0082773 · 3.23 Impact Factor
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ABSTRACT: Centrosomes are the key regulating element of cell cycle progression. Aberrations in their functional mechanism leads to several cancer related disorders. Although genomic studies in the field of centrosome have been extensively carried out, with the lack of structural conformation, the proteomic analysis of pathological genetic mutation is still a challenging task. Several computational algorithms and high range force fields are used to design the 3D structure conformation of proteins, which has now become the leading platform for in-silico drug discovery approaches. Application of these highly efficient platforms in centrosomics studies will be a novel approach to develop an efficient drug therapy for the treatment of their dysfunction disorders.
Gene 09/2012; 511(1). DOI:10.1016/j.gene.2012.09.040 · 2.14 Impact Factor
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