Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aflatoxin B1 (AFB1) has been postulated to be a hepatocarcinogen in humans, possibly by causing p53 mutations at codon 249. AFB1 is metabolized via the phase I and II detoxification pathways; hence, genetic variation at those loci may predict susceptibility to the effects of AFB1. To test this hypothesis, genetic variation in two AFB1 detoxification genes, epoxide hydrolase (EPHX) and glutathione S-transferase M1 (GSTM1), was contrasted with the presence of serum AFB1-albumin adducts, the presence of hepatocellular carcinoma (HCC), and with p53 codon 249 mutations. Mutant alleles at both loci were significantly overrepresented in individuals with serum AFB1-albumin adducts in a cross-sectional study. Mutant alleles of EPHX were significantly overrepresented in persons with HCC, also in a case-control study. The relationship of EPHX to HCC varied by hepatitis B surface antigen status and indicated that a synergistic effect may exist. p53 codon 249 mutations were observed only among HCC patients with one or both high-risk genotypes. These results indicate that individuals with mutant genotypes at EPHX and GSTM1 may be at greater risk of developing AFB1 adducts, p53 mutations, and HCC when exposed to AFB1. Hepatitis B carriers with the high-risk genotypes may be an even greater risk than carriers with low-risk genotypes. These findings support the existence of genetic susceptibility in humans to the environmental carcinogen AFB1 and indicate that there is a synergistic increase in risk of HCC with the combination of hepatitis B virus infection and susceptible genotype.
 ...
PMID:Susceptibility to hepatocellular carcinoma is associated with genetic variation in the enzymatic detoxification of aflatoxin B1. 789 76

The relative contribution of, and possible mechanism of interaction between, aflatoxin and hepatitis B virus (HBV) in the development of primary hepatocellular carcinoma can be better investigated now that markers of individual exposure to both factors are available. In this study, blood samples were collected over a 1-month period from 117 children aged 3 to 4 years, resident in Kuntair or Kerr Cherno in the Upper Niumi District of The Gambia. Samples were analyzed for aflatoxin-albumin (AF-alb) adducts, markers of HBV infection, liver enzymes [serum alanine aminotransferase (ALT)] as markers of liver damage, and glutathione S-transferase M1 genotype. All but two children showed detectable serum AF-alb with levels ranging from 2.2 to 250.4 pg aflatoxin B1-lysine equivalent/mg albumin. There was a significant positive correlation between AF-alb and ALT (r = 0.4; P < 0.001). HBV carriers showed moderately higher levels of AF-alb than noncarriers but the difference was not statistically significant and the association between AF-alb and ALT was unchanged when the HBV carriers were excluded from the analysis, suggesting that factors other than HBV infection contributed to the association. The null glutathione S-transferase M1 genotype was infrequent (17.7%) in this population and was not associated with any difference in AF-alb adduct levels compared to glutathione S-transferase M1-positive individuals. However, the percentage of individuals with the null genotype varied significantly between ethnic groups with 32.1% in Fula, 8.8% in Mandinka, and 13.3% in Wollof.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Aflatoxin, liver enzymes, and hepatitis B virus infection in Gambian children. 826 73

In order to assess associations between the genetic polymorphism of L-myc and glutathione S-transferase M1 (GST M1) and the risk of hepatocellular carcinoma (HCC), a total of 46 surgically treated HCC patients who were seropositive in hepatitis B surface antigen (HBsAg) and 88 HBs-Ag positive controls were recruited for this study. L-myc and GST M1 genetic polymorphism was examined using a polymerase chain reaction-based restriction fragment length polymorphism assay on DNA extracted from liver and peripheral blood samples. There was no significant difference in GST M1 genotypes between HCC patients and matched controls. A gene dosage trend of association with HCC risk was observed for L-myc genotype. The dose-response relationship remained statistically significant in the multiple logistic regression analysis.
 ...
PMID:L-myc, GST M1 genetic polymorphism and hepatocellular carcinoma risk among chronic hepatitis B carriers. 863 54

Hepatocellular carcinoma (HCC) is one of the major cancers in the world. There is a striking variation in HCC incidence rates between various countries, with a highest-to-lowest ratio of 112.5 for males and 54.7 for females. The high-risk populations are clustered in sub-Saharan Africa and eastern Asia. The male-to-female ratio for HCC ranges from < 1 to 6.4 and mostly from 2 to 4. There exist significant variations in the incidence of HCC among different ethnic groups living in the same area and among migrants of the same ethnic groups living in different areas. The age curves of HCC are significantly different in various countries, suggesting variability in exposure to risk factors. Chronic carriers of hepatitis B and C viruses (HBV and HCV, respectively) have an increased risk of HCC. The relative and attributable HCC risk of HBV and HCV carrier status varies in different countries. There exists a synergistic interaction on HCC between the two viruses. Aflatoxin exposure, cigarette smoking, heavy alcohol consumption, low vegetable intake, inorganic arsenic ingestion, radioactive thorium dioxide exposure, iron overload and the use of oral contraceptives and anabolic steroids have been documented as HCC risk factors. Recent molecular epidemiological studies have shown that low serum retinol levels as well as elevated serum levels of testosterone, neu oncoprotein and aflatoxin B1-albumin adduct are associated with an increased HCC risk. There is a synergistic interaction on HCC between chronic HBV infection and aflatoxin exposure. Familial aggregation of HCC exists and a major susceptibility gene of HCC has been hypothesized. Patients of some genetic diseases are at an increased risk of HCC. The genetic polymorphisms of cytochrome P450 2E1 and 2D6 and arylamine N-acetyltransferase 2 are associated with the development of HCC. A dose-response relationship between aflatoxin exposure and HCC has been observed among chronic HBV carriers who have null genotypes of glutathione S-transferase M1 or T1, but not among those who have non-null genotypes. Human hepatocarcinogenesis is a multistage process with the involvement of a multifactorial aetiology. Gene-environment interactions are involved in the development of HCC in humans.
 ...
PMID:Epidemiological characteristics and risk factors of hepatocellular carcinoma. 940 50

Dietary exposure to aflatoxins is one of the major risk factors for hepatocellular carcinoma. Individual susceptibility to aflatoxin-induced hepatocarcinogenesis may be modulated by both genetic and environmental factors affecting metabolism. A cross-sectional study was performed to evaluate determinants of the formation of aflatoxin covalently bound to albumin (AFB1-albumin adducts). A total of 474 subjects who were free of liver cancer and cirrhosis and were initially selected as controls for previous case-control studies of aflatoxin-induced hepatocarcinogenesis in Taiwan, were employed in this study. Aflatoxin-albumin adducts were determined by competitive enzyme-linked immunosorbent assay, hepatitis B surface antigen and antibodies to hepatitis C virus by enzyme immunoassay, as well as genotypes of glutathione S-transferase M1-1 and T1-1 by polymerase chain reaction. The detection rate of AFB1-albumin adducts was significantly higher in males (42.5%) than in females (21.6%) (multivariate-adjusted odds ratio=2.6, 95% confidence interval=1.4-5.0). The formation of detectable albumin adducts was moderately higher in hepatitis B surface antigen carriers (42.8%) than in non-carriers (36.6%) (multivariate-adjusted odds ratio=1.4, 95% confidence interval=1.0-2.1). In addition, the detection rate of AFB1-albumin adducts tended to increase with the increasing number of null genotypes of glutathione S-transferase M1-1 and glutathione S-transferase T1-1. In conclusion, this cross-sectional study has assessed the relative contributions of environmental exposure and host susceptibility factors in the formation of AFB1-albumin adducts in a well characterised Chinese adult population. This study further emphasises the necessity to reduce aflatoxin exposure in people living in an area endemic for chronic hepatitis B virus infection.
 ...
PMID:Determinants of formation of aflatoxin-albumin adducts: a seven-township study in Taiwan. 1243 85

Our aim was to evaluate the role of N-acetyltransferase (NAT2) and glutathione S-transferase M1 and T1 (GSTM1 and GSTT1) polymorphisms in hepatocellular carcinoma (HCC) according to cigarette smoking, taking into account hepatitis B (HBV) and C (HCV) viral infection as well as alcohol consumption. A hospital-based case-control study was conducted in 2 areas of north Italy. Cases (n = 200) were patients hospitalized for HCC, and controls (n = 400) were patients admitted for reasons other than liver disease, neoplasms and tobacco- and alcohol-related diseases. Genotypes were determined using PCR and the PCR/restriction fragment length polymorphism-based method. The putative risk genotypes NAT2 slow acetylator, GSTM1 null and GSTT1 null were not associated with HCC (OR = 1.3, 95% CI 0.8-2.0; OR = 1.0, 95% CI 0.6-1.5; OR = 0.8, 95% CI 0.4-1.4, respectively). Although not statistically significant, an increase in HCC risk was observed among light smokers (1-20 pack-years) carrying GSTT1 null (OR = 1.7, 95% CI 0.6-4.7) and NAT2 slow acetylator (OR = 1.3, 95% CI 0.6-3.0) genotypes. In conclusion, there was no evidence for a gene-environment interaction in HCC risk for GSTM1, GSTT1 and NAT2 genotypes.
 ...
PMID:N-Acetyltransferase-2, glutathione S-transferase M1 and T1 genetic polymorphisms, cigarette smoking and hepatocellular carcinoma: a case-control study. 1568 97