Determinants of the variability of aflatoxin-albumin adduct levels in Ghanaians.
Hepatocellular carcinoma (HCC) is a multifactorial disease with various host and environmental factors involved in its etiology. Of these, aflatoxin exposure has been established as an important risk factor in the development of HCC; the presence of aflatoxin-albumin (AA) adducts in the blood serves as a valuable biomarker of human exposure. In this study, the relationship between a variety of different HCC host factors and the incidence of AA adduct levels was examined in a Ghanaian population at high risk for HCC. These factors included age, gender, hepatitis virus B (HVB) and hepatitis C virus (HCV) status, and genetic polymorphisms in both microsomal epoxide hydrolase (mEH) and glutathione S-transferases (GSTs). Blood samples were analyzed for AA adducts and HBV and HCV status. GSTM1 and GSTT1 deletion polymorphisms and mEH exon 3 and exon 4 single-nucleotide polymorphisms (SNPs) were determined from urine samples. In univariate analysis, age, HBV and HVC status, and GSTT1 and mEH exon 3 genotypes were not associated with AA adduct levels. However, mean adduct levels were significantly higher in both females and individuals typed heterozygous for mEH exon 4 (vs. wild types). Stratification analysis also showed that gender along with mEH exon 4 genotype and HBV status had a significant effect on adduct levels. Both females typed HBsAg+ and males with mEH exon 4 heterozygote genotypes showed significantly higher adduct levels as compared to the HBsAg- and wild types, respectively. Understanding the relationships between these host factors and the variability in aflatoxin-adduct levels may help in identifying susceptible populations in developing countries and for targeting specific public health interventions for the prevention of aflatoxicoses in populations with HCC and chronic liver diseases.
Dash
B
B
Faculty of Toxicology, Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas 77843, USA.
Afriyie-Gyawu
E
E
Huebner
H J
HJ
Porter
W
W
Wang
J S
JS
Jolly
P E
PE
Phillips
T D
TD
D000328:Adult; D000348:Aflatoxins / Q000378:metabolism*; D000367:Age Factors; D000368:Aged; D004784:Environmental Monitoring; D005260:Female; D005869:Ghana; D005982:Glutathione Transferase / Q000235:genetics; D006509:Hepatitis B; D006526:Hepatitis C; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012709:Serum Albumin / Q000378:metabolism*; D012737:Sex Factors; D000096702:Aflatoxin Poisoning
D000348:Aflatoxins; D005982:Glutathione Transferase; D012709:Serum Albumin; C413545:glutathione S-transferase T1