Role of genetic polymorphism of glutathione-S-transferase T1 and microsomal epoxide hydrolase in aflatoxin-associated hepatocellular carcinoma.

Exposure to aflatoxins is a risk factor for hepatocellular carcinoma (HCC). Aflatoxins occur in peanut butter and are metabolized by genetically polymorphic enzymes such as glutathione-S-transferases encoded by glutathione-S-transferase mu 1 gene (GSTM1) and glutathione-S-transferase theta 1 gene (GSTT1) and microsomal epoxide hydrolase encoded by epoxide hydrolase gene (EPHX). The rate at which aflatoxins become activated or detoxified may depend on polymorphisms in the encoding genes. GSTM1 homozygous deletion was indeed found to modify the association between peanut butter consumption and HCC. In this study, we investigate possible roles of GSTT1 and EPHX polymorphisms in this relationship. From a Sudanese case-control study on HCC, we analyzed data of 112 incident cases and 194 controls. All participants were interviewed using a standardized questionnaire inquiring about social and demographic factors, peanut butter consumption, and other known HCC risk factors. Univariate analysis showed that GSTT1 polymorphism was not associated with HCC, whereas EPHX 113HH and 139HH genotypes increased the risk of HCC (Odds ratio, 3.10; 95% Confidence interval, 1.18-8.12). Adjustment for age and region of origin slightly attenuated this association (Odds ratio, 2.56; 95% Confidence interval, 0.83-7.95). Interestingly, unlike GSTM1, both GSTT1 and EPHX polymorphism did not modify the association between peanut butter consumption and HCC. In conclusion, these epidemiological findings do not suggest significant roles of GSTT1 and EPHX in aflatoxin metabolism, although EPHX polymorphism is possibly related to the increased risk of HCC. Further studies are needed to investigate mechanisms by which the EPHX polymorphism potentially modifies cancer risk.

The role of hepatitis B and hepatitis C viral infections in the incidence of hepatocellular carcinoma in Sudan.

In Sudan, the incidence of hepatocellular carcinoma (HCC) is high and increasing. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are important risk factors of HCC. This study aims to assess the role of HBV and HCV infections in the incidence of HCC in 2 regions of Sudan. A case-control study was conducted in 1996-98 among 150 HCC patients and 205 controls from 2 regions in Sudan. Their demographic characteristics as well as food habits and chronic conditions have been investigated. In this study, 115 cases and 199 controls were tested for hepatitis B surface antigen (HBsAg) and for HCV antibodies. Strong positive associations were found between HBV or HCV, and HCC with odds ratios (ORs) 9.8 (95% CI 5.1-18.9) and 8.3 (95% CI 2.3-29.9), respectively. After adjustment for age, by logistic regression, the ORs for HBV and HCV were 16.1 (95% CI 7.4-34.9) and 4.5 (95% CI 1.1-18.6), respectively. Further adjustment for region, education level and job type did not appreciably affect the results. Given a prevalence of HBV and HCV of 7.0% and 1.5% among controls, about 57% of all HCC cases can be attributed to these viral infections. Hepatitis infections seem to be important risk factors for HCC in Sudan.

Peanut butter intake, GSTM1 genotype and hepatocellular carcinoma: a case-control study in Sudan.

OBJECTIVE: Hepatocellular carcinoma (HCC) is one of the major cancers in the world. In Sudan the incidence is thought to be high and increasing. This study aims to assess the association between peanut butter intake, as a source of aflatoxins, and the GSTM1 genotype in the etiology of HCC. METHOD: A case control study was conducted among 150 patients and 205 controls from two regions in Sudan. Food habits with special reference to peanut butter consumption, as well as peanut storage systems, have been investigated, as well as confounders such as hepatitis, drinking and smoking habits, and demographic characteristics. GSTM1 genotype was assessed in DNA extracted from blood samples (110 cases, 189 controls). RESULTS: A positive association was observed for highest vs. lowest quartile of peanut butter intake, humid storage system and HCC, with ORs (95% CI) being 3.0 (1.6-5.5) and 1.6 (1.1-2.5) respectively. The positive association with peanut butter intake was essentially limited to subjects with GSTM1 null genotype with OR for highest vs. lowest quartile 16.7 (2.7-105). CONCLUSION: Peanut butter consumption has been identified as a strong risk factor of HCC in a region with endemic aflatoxin contamination in Sudan and was essentially limited to subjects with the GSTM1 null genotype.

Aflatoxin and liver cancer in Sudan.

This study investigated whether aflatoxin contamination of peanut products may contribute to the incidence of hepatocellular carcinoma (HCC) in Sudan. Thirty-seven peanut butter and peanut samples were collected from local markets. Aflatoxin concentrations were significantly higher in West Sudan [87.4 +/- 197.3 (SD) micrograms/kg], a high-risk area, than in Central Sudan (8.5 +/- 6.8 micrograms/kg), a low-risk area. In West Sudan, humid local storage conditions of peanut products were related to high aflatoxin concentrations. In a small case-control study of HCC patients (n = 24) and controls (n = 34), an odds ratio of 7.5 (95% confidence interval = 1.4-40.2) was observed for humid vs. dry local storage conditions. Development of an index of individual HCC exposure was less successful, probably because of year-to-year variability in aflatoxins in food. These preliminary findings justify further research into the role of aflatoxins and hepatitis in HCC incidence in Sudan.