-
[show abstract]
[hide abstract]
ABSTRACT: For decades of years, hundreds of candidate gene-based association studies explored the relationship between single nucleotide polymorphisms (SNPs) and hepatocellular carcinoma (HCC). There was no systematic review summarized the results of these association studies of candidate SNPs and HCC to date. In order to summarize the results of the association studies, we conducted a concise systematic review.
By searching Pubmed database before October 2010, we reviewed all the association studies about candidate SNPs and HCC. If the eligible study number on a given SNP was more than three, we conducted a meta-analysis. We reported here only the overall positive-association results with statistical significance and evaluated the reliability of the associations by using false-positive report probability (FPRP) analysis and the Venice guidelines on genetic epidemiology studies.
Six SNPs of five genes (rs1800562 of HFE, rs17868323 and rs11692021 of UGT1A7, rs2279744 of MDM2, rs1143627 of IL-1B, and rs4880 of MnSOD) showed overall significant associations with HCC. The eligible number of the studies varied from three to nine. Two SNPs (rs1800562 of HFE and rs2279744 of MDM2) passed the FPRP threshold (FPRP < 0.20). According to the Venice guidelines, the associations between the two SNPs (rs1800562 and rs2279744) and HCC were of moderate evidence.
Two SNPs (rs1800562 of HFE and rs2279744 of MDM2) were associated with HCC with moderate epidemiological evidence and deserve further study and additional biological and clinical assessment.
Journal of Cancer Research and Clinical Oncology 01/2011; 137(7):1095-104. · 2.56 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Aim: To investigate the roles of biomedical factors, hepatitis B virus (HBV) DNA levels, genotypes, and specific viral mutation patterns on the progression of hepatocellular carcinoma (HCC) in Qidong, China. Methods: A total of 2387 males (aged 20-65 years) who were seropositive for the hepatitis B surface antigen (HBsAg), but had not been diagnosed with HCC, were recruited to a community-based HCC screening study from August, 1996. Evaluation of virological parameters at recruitment was determined for 196 HCC patients during 10 years of follow-up and 323 controls. Results: After adjustment for age at recruitment, history of cigarette smoking and alcohol consumption, alanine aminotransferase (ALT) elevation, alpha-fetoprotein (AFP) levels >20 ng/mL, hepatitis B e antigen positive, HBV DNA levels ≥4.00 log(10) copies/mL, pre-S deletion, T1653 mutation, T1762/A1764 double mutations, and T1766 and/or A1768 mutations were associated with subsequent risk of HCC. A significant biological gradient of HCC risk by HBV DNA levels from less than 2.69 log(10) copies/mL to 6.00 log(10) copies/mL or greater was observed. HBV with a complex mutation combination pattern (pre-S deletion, T1762/A1764 double mutations, and T1766 and/or A1768 mutations) rather than a single mutation was associated with the development of HCC. The longitudinal observation demonstrated a gradual combination of pre-S deletion, T1762/A1764 double mutations, and T1766 and/or A1768 mutations during the development of HCC. Conclusions: AFP levels >20 ng/mL, high HBV DNA levels, pre-S deletion, and T1762/A1764 double mutations at recruitment were independent risk factors of HCC. Combination of pre-S deletion and core promoter mutations increased the risk of HCC.
Hepatology Research 10/2010; 41(1):54-63. · 2.20 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A retrospective cohort study was conducted to investigate the effect of interferon-α (IFN-α) therapy after curative resection on survival and recurrence in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).
Of 568 HBV-related HCC patients who underwent curative resection, 101 patients received postoperative IFN-α therapy (5 million units three times every week for 18 months). Clinicopathological factors were compared between patients with postoperative IFN-α therapy or not. Risk factors for survival, early, and late recurrence (2 years as cut-off) were studied.
The median follow-up time was 53.3 months. There was no significant difference in clinicopathological factors between the two groups. Patients with postoperative IFN-α therapy had higher overall survival rates (hazards ratio (HR): 0.612, 95% confidence interval (CI): 0.422-0.889, P = 0.010). No significant difference in disease-free survival rates was detected between the two groups (HR: 0.786, 95% CI: 0.597-1.035, P = 0.086). Multivariate analysis revealed that postoperative IFN-α therapy was an independent factor for overall survival (HR: 0.611, 95% CI: 0.421-0.887, P = 0.010) and significantly reduced early recurrence (HR: 0.562, 95% CI: 0.375-0.840, P = 0.005).
IFN-α therapy after curative resection prevented early recurrence and improved overall survival of patients with HBV-related HCC.
Journal of Surgical Oncology 09/2010; 102(7):796-801. · 2.10 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A retrospective cohort study was conducted to identify risk factors for recurrence of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative resection. A total of 317 patients who had received curative resection of pathologically proven small HCC (< or = 3 cm in diameter) were analyzed to ascertain the factors affecting recurrence. The median follow-up period was 33.7 months. Cumulative recurrence rates at 1, 3, and 5 years after resection were 23.5%, 49.5%, and 65.5%, respectively. Male sex, alpha-fetoprotein (AFP) > or = 400 ng/mL, HBV DNA level > or = 4 log(10) copies/mL, prolonged prothrombin time, tumor size > or = 2 cm, microvascular invasion, absence of capsular formation, moderate/poor tumor differentiation, and absence of postoperative interferon-alpha (IFN-alpha) treatment were associated with increased cumulative risk of HCC recurrence. By multivariate analysis, HBV DNA level > or = 4 log(10) copies/mL (P < 0.001, hazard ratio (HR) 2.110), AFP > or = 400 ng/mL (P = 0.011, HR 1.574), microvascular invasion (P < 0.001, HR 1.767), and postoperative IFN-alpha treatment (P = 0.022, HR 0.562) remained to be independently associated with HCC recurrence. Those contributing to late recurrence (>2 years) were older age and HBV DNA level > or = 4 log(10) copies/mL. Patients with persistent HBV DNA level > or = 4 log(10) copies/mL at resection and follow-up had the highest recurrence risk (P < 0.001, HR 4.129). HBV DNA level > or = 4 log(10) copies/mL at the time of resection was the most important risk factor for recurrence. Postoperative IFN-alpha treatment significantly decreased the recurrence risk after resection.
Journal of Gastrointestinal Surgery 07/2010; 14(7):1111-20. · 2.83 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Hereditary hemochromatosis (HH) is an autosomal recessive disorder mainly associated with homozygosity for the C282Y and H63D mutations in the hemochromatosis (HFE) gene. The reports about the C282Y and H63D mutations and hepatocellular carninoma (HCC) were controversial. To clarify the relationship between C282Y and H63D mutations and HCC, a meta-analysis including nine studies (1102 HCC cases and 3766 controls, mainly came from European populations) was performed.
The association was measured using random-effect (RE) or fixed-effect (FE) odds ratios (ORs) combined with 95% confidence intervals (CIs) according to the studies' heterogeneity.
Meta-analysis of nine studies showed that Y allele of C282Y was associated with HCC risk: RE OR reached 1.50 (95%CI: 1.05-2.14, p for heterogeneity = 0.02, I2 = 0.57). Subgroup analysis of seven studies also showed Y allele was associated with HCC risk in healthy populations: RE OR reached 1.61 (95%CI: 1.08-2.39, p for heterogeneity = 0.04, I2 = 0.55). We further did subgroup analysis in alcoholic liver cirrhosis (LC) patients of four studies (224 cases and 380 controls) and found that both the dominant model and Y allele of C282Y were associated with HCC risk (FE OR reached 4.06, 95%CI: 2.08-7.92 and 3.41, 95%CI: 1.81-6.41, respectively). There was no distinct heterogeneity among the studies (I2 = 0). Sensitivity analyses showed the results were robust in the subgroup analysis of alcoholic LC patients.
C282Y mutation was associated with HCC in European alcoholic LC patients.
Journal of Experimental & Clinical Cancer Research 03/2010; 29:18. · 2.15 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Methylenetetrahydrofolate 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.
The 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.
Using 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.
MTHFR 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.
Diagnostic Pathology 11/2009; 4:39. · 1.64 Impact Factor
