Genetic risk of hepatocellular carcinoma in patients with hepatitis C virus: A case control study
ABSTRACT 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.
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ABSTRACT: During the past decade, a number of studies were published to evaluate the association between murine double minute 2 (MDM2) T309G polymorphism and risk of liver cancer. However, the association between MDM2 T309G polymorphism and risk of liver cancer was still unclear owing to the conflicting results from those published studies. An undated meta-analysis of all eligible studies was carried out to comprehensively assess the association. The pooled odds ratio (OR) with 95 % confidence interval (95 % CI) was used to evaluate the association between MDM2 T309G polymorphism and risk of liver cancer. Finally, ten studies with a total of 2,243 cases and 3,471 controls were finally included into the meta-analysis. Overall, there was an association between MDM2 T309G polymorphism and risk of liver cancer (G vs. T: OR = 1.39, 95 % CI 1.17-1.64, P < 0.001; GG vs. TT: OR = 1.87, 95 % CI 1.34-2.62, P < 0.001; GG/GT vs. TT: OR = 1.61, 95 % CI 1.24-2.08, P < 0.001). Subgroup analysis in Europeans showed that there was also an association between MDM2 T309G polymorphism and risk of liver cancer in Europeans (G vs. T: OR = 1.81, 95 % CI 1.45-2.27, P < 0.001; GG vs. TT: OR = 3.26, 95 % CI 1.99-5.32, P < 0.001; GG/GT vs. TT: OR = 2.20, 95 % CI 1.58-3.07, P < 0.001). Subgroup analysis in Asians showed that there was also an association between MDM2 T309G polymorphism and risk of liver cancer in Asians (G vs. T: OR = 1.27, 95 % CI 1.06-1.52, P = 0.010; GG vs. TT: OR = 1.59, 95 % CI 1.11-2.27, P = 0.011; GG/GT vs. TT: OR = 1.41, 95% CI 1.07-1.87, P = 0.016). The meta-analysis provides a strong evidence for the association between MDM2 T309G polymorphism and risk of liver cancer.Tumor Biology 08/2014; DOI:10.1007/s13277-014-2432-9 · 2.84 Impact Factor
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ABSTRACT: A number of studies have investigated associations of genetic variation in RAD23B Ala249Val (rs1805329 C>T) with cancer susceptibility; however, the findings are inconsistent. We performed a meta-analysis to acquire a more precise estimation of the relationship. We searched literatures from PubMed, Embase and Web of Science. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the association between Ala249Val polymorphism and cancer risk. A total of 23 studies consisting of 10837 cases and 13971 controls were included in this meta-analysis. Overall, no significant associations were found between RAD23B Ala249Val polymorphism and cancer risk (Val/Val vs. Ala/Ala: OR = 0.97, 95% CI = 0.75-1.25; Ala/Val vs. Ala/Ala: OR = 1.08, 95% CI = 0.96-1.22; recessive model: OR = 0.93, 95% CI = 0.76-1.14 and dominant model: OR = 1.07, 95% CI = 0.94-1.20). We did not find any significant associations in the further stratification analyses by cancer type, ethnicity and source of control. Despite some limitations, this meta-analysis indicates that it is unlikely that the RAD23B 249Val/Val polymorphism may contribute to the individual susceptibility to cancer risk. However, further advanced designed studies with larger sample size and different ethnicities should be conducted to confirm our results.PLoS ONE 03/2014; 9(3):e91922. DOI:10.1371/journal.pone.0091922 · 3.53 Impact Factor
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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