Field studies of aflatoxin exposure, metabolism and induction of genetic alterations in relation to HBV infection and hepatocellular carcinoma in The Gambia and Thailand

Abstract

The relative contribution of aflatoxins (AF) and hepatitis B virus (HBV) to the aetiology of liver cancer remains to be determined, as does the mechanism of any interaction between these two factors. Methods to measure individual exposure to AF permit the assessment of this possible interaction in field studies. The measurement of AF covalently bound to albumin in peripheral blood has been particularly useful in this respect. In east and west African countries the majority (75-100%) of individuals has been found positive (> 5 pg AFB1-lysine eq./mg albumin) for the AF-albumin adduct with levels ranging up to 720 pg/mg. Levels of adduct to date have been age- and sex-independent, although marked seasonal variations were seen in The Gambia. Exposure also occurs in utero, with the AF-adduct being found in umbilical cord blood. In a study in The Gambia involving 323 children (age 3-8 years) the AF-albumin adduct levels were examined with respect to HBV infection and ethnic group. Over 95% of all sera contained detectable adduct but children positive for HBV surface antigen (HBsAG) had significantly higher adduct levels than children with markers of past infection or who had never been infected (mean (log) AF-albumin adduct levels 4.41 +/- 0.95, 4.04 +/- 0.99, and 4.05 +/- 1.03 respectively, p = 0.04). In addition, there were highly significant differences in adduct levels between the three major ethnic groups (Wollof 4.41 +/- 0.69: Fula 4.05 +/- 1.1; Mandinka 3.7 +/- 1.14). Wollof children were also more likely to be HBsAg positive than the other two groups. These data suggest that ethnic group and HBV infection can influence AF metabolism and this is being examined in this population with respect to genetic polymorphisms in cytochrome P450 and glutathione-S-transferase enzymes. In addition, these biomarkers are being compared to the nature and frequency of mutations in somatic and tumour cells.