Role of aflatoxin B1 as a risk for primary liver cancer in north Indian population.

OBJECTIVES: The present study was designed to determine whether aflatoxin B1 (AFB1) exposure has any role to play in hepatocellular carcinoma (HCC) patients from northern India. DESIGN AND METHODS: A total of 266 HCC patients and 251 patients of chronic liver disease without-HCC were enrolled into the study. All samples were screened for serological markers for hepatitis B and C infections and levels of AFB1 in food and urine samples. RESULTS: A threefold (OR=3.43) and five-fold (OR=5.47) increased risk of HCC was observed amongst HBV infection and AFB1-levels in food and urine samples, respectively. However, a non-significant risk was observed with respect to HCV infection (OR=1.27) and alcohol consumption (OR=1.18). A threefold (OR=3.15) increased risk of HCC was observed amongst cases of non-viral etiology with respect to urinary AFB1. CONCLUSION: The data provides an exposure and disease risk information for establishing intervention studies to diminish the impact of aflatoxin exposure in Indian population.

Genetic polymorphism of glutathione S transferases M1 and T1 in Indian patients with hepatocellular carcinoma.

OBJECTIVE: Our aim was to evaluate whether the association of GSTM1/T1 gene polymorphisms modifies the risk of Hepatocellular carcinoma (HCC) and what is its correlation with other predisposing risk factors like alcohol intake, cigarette smoking and hepatitis B and C infections. STUDY DESIGN/SETTING: It was a case-control study, included 254 HCC cases compared with 525 hospital-based age and sex matched cases of chronic liver disease without HCC as controls from Indian population. The GSTM1 and GSTT1 genotypes were detected using conventional multiplex PCR method. RESULTS: In this case-control study, we observed a positive correlation between age, HBV and HCV infection, smoking habit of > 20 packs/year, alcohol consumption of > 100 g/day and risk of liver cancer. We found significantly increased risk associated with GSTM1 null genotype (OR = 3.49; 95% CI = 2.52-4.84) as well as GSTT1 null genotype (OR = 3.12; 95% CI = 2.19-4.45), respectively. However, an increased risk of HCC was observed among heavy drinkers with GSTM1 (OR = 2.01; 95% CI = 1.11-3.66). Further, cigarette smoking showed a non-significant association with GSTT1 (OR = 1.49; CI = 0.69-3.25). CONCLUSION: Our results suggest that the variants in low penetrance gene such as GSTM1 and GSTT1 are associated with an increased liver cancer risk. Further, an influence of GSTM1/T1 null genotypes may contribute in the etiology of HCC in patients with higher cigarette and alcohol consumption.

Hepatitis B virus BCP, Precore/core, X gene mutations/genotypes and the risk of hepatocellular carcinoma in India.

The study aims to characterize mutations of the HBV genome involving BCP, Precore/core and X regions and also defines HBV genotypes in patients of hepatocellular carcinoma (HCC). The study involved 150 HBV-related HCC cases and 136 HBV-related chronic liver disease patients without HCC as controls. HBV DNA was subjected to mutational analysis using SSCP technique, genotyping by RFLP, and direct nucleotide sequencing. HBV DNA was found in 58.7% (88/150) of the HCC cases and 74.3% (101/136) of controls. HBV mutants were observed in 44.3% of HCC cases and 43.2% of controls. HBV/D was prevalent amongst the patients and controls, followed by HBV/A. The prevalence of the TT1504 mutation in the X gene, the V1753 and T1762/A1764 mutations in the BCP region, and G1914 mutation in the core gene were significantly higher in the HCC group than in the non-HCC group. Multivariate analyses showed that the TT1504, V1753, A1762T/G1764A, and the G1914 mutations and the patient's age, sex, and HBeAg status increased the risk of HCC development significantly. Also, patients with HCC had lower levels of serum albumin, viral load, and platelet counts but higher values of alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, bilirubin, and Alpha feto-protein than those of controls (P < 0.001 for all comparisons). HBV/D was the predominant genotype associated with HCC cases seen in India. The presence of different types of HBV mutations, age, sex, HBeAg status, and viral load was found to increase significantly the risk of HCC development in India.