ABSTRACT
A case-control study was carried out to investigate the impact of factors including virus infection, aflatoxin B1, microcystins, smoking/drinking and dietary habits as well as genetic polymorphisms of aldehyde dehydrogenase 2 (ALDH2) and cytochrome P4502E1 (CYP2E1), on susceptibility to hepatocellular carcinoma (HCC) in Haimen, China. A total of 248 patients with HCC and 248 sex-, age- and residence-matched population-based controls were recruited into the study. Virus infection, and ALDH2 and CYP2E1 gene polymorphisms were assessed in 134 paired cases and controls. By univariate analysis, hepatitis B virus (HBV) infection (odds ratio [OR]=9.75; 95% confidence interval [CI]=4.71-20.2), history of intravenous injection (OR=1.50; 95%CI=1.02-2.22), average income (OR=0.63; 95%CI=0.43-0.92), frequent intake of foods rich in protein, e.g., egg (OR=0.6; 95%CI=0.42-0.87), chicken (OR=0.53; 95%CI=0.35-0.79), pork (OR=0.67; 95%CI=0.46-0.98) and fresh fish (OR=0.58; 95%CI=0.39-0.87) significantly differed between cases and controls. However, peanut intake (OR=0.66; 95%CI=0.43-1.01), source of drinking water, including tap (OR=1.33; 95%CI=0.81-2.20), deep well (OR=0.94; 95%CI=0.56-1.55), shallow well (OR=0.85; 95%CI=0.55=1.30), river (OR=0.95; 95%CI=0.65-1.38), ditch (OR=1.09; 95%CI=0.76-1.55) and pond water (OR=1.0; 95%CI=0.14-7.10) were not significantly associated with risk. Univariate analysis also indicated that the 1-1 genotype of ALDH2 (OR=1.38; 95%CI=0.86-2.23) as well as the Pst1- and Rsa1-digested c1/c1 genotype of CYP2E1 (OR=1.36; 95%CI=0.81-2.28), was slightly more frequent in the case group. On multivariate analysis, HBV infection (OR=13.9; 95%CI=5.78-33.6) and history of intravenous injection (OR=2.72; 95%CI=1.24-6.00) were still associated with significantly increased risk of HCC, while frequent intake of fresh fish (OR=0.32; 95%CI=0.12-0.86) decreased this risk. These findings suggest that whereas peanut intake, water sources as well as genetic polymorphisms in ALDH2 and CYP2E1 do not significantly correlate with the risk of HCC, HBV infection is a main risk factor, and dietary items rich in protein, especially fresh fish, might protect against the risk of HCC in Haimen, China.
Subject(s)
Carcinoma, Hepatocellular/etiology , Hepatitis B/complications , Hepatitis C/complications , Life Style , Liver Neoplasms/etiology , Polymorphism, Genetic , Adult , Aflatoxin B1/toxicity , Aged , Alcohol Drinking/adverse effects , Aldehyde Dehydrogenase/genetics , Aldehyde Dehydrogenase, Mitochondrial , Cytochrome P-450 CYP2E1/genetics , Female , Food Contamination , Humans , Male , Middle Aged , Risk Factors , Smoking/adverse effectsABSTRACT
Primary hepatocellular carcinoma (HCC) is a significant cause of cancer morbidity and mortality on the global scale. Although epidemiologic studies have identified major risk factors for HCC, the sequence of oncogenic events at the molecular level remains poorly understood. While genetic allele loss appears to be a common event, the significance of the loss is not clear. In order to determine whether allele loss appears to be a random event among HCCs or whether patterns of loss cluster in groups of tumors, a phylogenetic approach was used to examine 32 tumors for genome-wide loss of heterozygosity employing 391 markers. Clusters identified by the phylogenetic analysis were then contrasted to compare candidate locus variation among individuals and to determine whether certain clusters exhibited higher loss rates than other clusters. The analysis found that 3 major and 1 minor cluster of loss could be identified and, further, these clusters were distinguished by variable rates of loss (cluster 1, 29%; cluster 2, 21%; cluster 3, 16%). The analyses also indicated that the allele loss rates in HCC were not insignificant and that the patterns of allele loss were complex. In addition, the results indicated that an individual's constitutional genotype at the EPHX1 locus may be a critical factor in determining the path of tumor evolution. In conclusion, it appears that in HCC, allele loss is not random, but clusters into definable groups that are characterized by distinctive rates of loss.
Subject(s)
Carcinoma, Hepatocellular/genetics , Genetic Heterogeneity , Liver Neoplasms/genetics , Phylogeny , Adult , Aged , Alleles , Carcinoma, Hepatocellular/epidemiology , Female , Genetic Predisposition to Disease/epidemiology , Humans , Liver Neoplasms/epidemiology , Loss of Heterozygosity , Male , Middle Aged , Risk FactorsABSTRACT
AIM:In order to study the association between the null genotypes of GSTM1 and GSTT1 and the genetic susceptibility to hepatocellular carcinoma (HCC).METHODS:The genotypes of GSTM1 and GSTT1 of 63 cases of HCC and 88 controls were detected with the multiple PCR technique.RESULTS:The frequency of GSTM1 null genotype was 57.1% among the cases, and 42.0% among the controls, the difference being statistically significant (X(2) = 3.35, P = 0.067), but X(2) value approaching the significance level. The odds ratio was 1.84 (95% CI = 0.91-3.37). The frequency of GSTT1 non-null genotype was 87.3% among the cases and 62.5% among the controls, the difference being statistically significant (X(2) = 11.42, P = 0.0007274). The odds ratio was 4.13 (95% CI = 1.64-10.70).According to the cross analysis, the GSTT1 non null genotype was more closely associated with HCC than GSTM1 null genotype, and these two factors play an approximate additive interaction in the occurrence of HCC.CONCLUSION:The persons with GSTM1 null genotype and GSTT1 non-null genotype have the increased risk to HCC.
