Contribution of HBV and aflatoxin exposureto the pathogenesis of hepatocellular carcinomas in gene level

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world, as fifth in males and seventh in females, accounting for 70-90% of primary liver cancer cases. Chronic Hepatitis B Virus (HBV) infection prevalence and high aflatoxin exposure are important risk factors for HCC. On the other hand, it is speculated, especially since the long time that food-derived aflatoxin and its metabolites contribute neoplastic changes in the liver or contribute as a cofactor. Our study will evaluate the roles of Aflatoxin B1 (AFB1) and HBx in patients with chronic HBV, especially on the development of HCC in our region, which is open to food and aflatoxin exposure due to climate and nutritional type. The synergistic relationship between HBV and Aflatoxin which are thought to be important in hepatotoxicity, for mutations in the P53 gene region, will be questioned and molecular mechanisms will be investigated. For this purpose, we will investigate the presence of the gene region encoding Hbx oncoprotein and AFB1 level in the paraffin-embedded liver biopsy specimens of HCC patients with chronic HBV after deparafinization. The synergistic effect of HBV and AFB1 on HCC risk will be determined using the hotspot mutation frequency by DNA sequence analysis of the tumor suppressor p53 gene at codon 249 or by PCR-RFLP method as B plan. As a result of our study, aflatoxin exposure status in the HCC patients in our region and the importance of Aflatoxin B1 as a risk factor in the development of HCC will be determined. Significant data to be considered in the treatment of HCC patients with chronic HBV infection will be provided.The mean urine AFM1 concentration levels of the individuals in the HSK + HBV patient group were 0.130absorbance / 2600pg / ml in the patient urine and 0.1799 absorbance / 1600 pg / mL in the control group compared to the mean concentration levels in the healthy subjects, 3 (14.2%) of the individuals in the control group and 4 (11.4%) in the patient group remained below the AFM1 detection level. DNA samples in which R249S mutation was detected, 6/35 (17.1%) and 5 (14.3%) samples of HCC patients, among the healthy individuals, only two (9.6%) were found to have AGG> AGT mutations at the relevant codon in tumor suppressor gene p53 with both method.PCR-RFLP mutation was detected in all 6 individuals, 5 of whom had HCC, whose DNA sequence analysis method detected R249S mutation in the p53 gene.In the patient group the lowest and highest AFM1 concentration was 1340pg / ml and 5015pg / ml, respectively.