Environmental and genetic determinants of aflatoxin-albumin adducts in the Gambia.
Aflatoxins together with chronic hepatitis B virus (HBV) infection contribute to the high incidence of hepatocellular carcinoma in developing countries. An understanding of the mechanism of interaction between these factors would provide a strong rationale for developing effective prevention strategies. In this study in The Gambia we examined the effect of environmental (place of residence and timing of sample collection) and host factors (age, sex, HBV status and interindividual variations in carcinogen metabolising enzymes) in determining blood aflatoxin-albumin adduct levels in 357 individuals of whom 181 were chronic HBV carriers. Samples were analysed for aflatoxin-albumin adducts, HBV status and genotypes of glutathione S-transferase (GST) M1, GSTT1, GSTP1 and epoxide hydrolase (EPXH). Urine samples were analysed for 6beta-hydroxycortisol:cortisol ratio as a marker of cytochrome P450 (CYP) 3A4 activity. Adduct levels were significantly higher in subjects resident in rural [geometric mean adduct level 34.9 pg aflatoxin B1-lysine equivalent (28.5-42.8; 95%CI)/mg albumin] than in periurban areas [22.2 pg (14.9-33.4)/mg] and were approximately twice as high in the dry season [mid-February to March; 83.2 pg (53.3-130.8)/mg] than the wet [July to August; 34.9 pg (28.5-42.8)/mg]. In contrast, HBV status, CYP3A4 phenotype, GSTT1, GSTP1 and EPXH genotypes were not associated with aflatoxin-albumin adduct level. However, mean adduct levels were significantly higher in non-HBV infected subjects with GSTM1 null genotype. The main factors which affect aflatoxin-albumin adduct levels in this population are environmental, notably place of residence and timing of sample collection. This study further emphasises the priority to reduce aflatoxin exposure in these communities by primary prevention measures.
Wild
C P
CP
Molecular Epidemiology Unit, School of Medicine, University of Leeds, UK. c.p.wild@leeds.ac.uk
Yin
F
F
Turner
P C
PC
Chemin
I
I
Chapot
B
B
Mendy
M
M
Whittle
H
H
Kirk
G D
GD
Hall
A J
AJ
D000293:Adolescent; D000328:Adult; D016604:Aflatoxin B1 / Q000378:metabolism*; D003430:Cross-Sectional Studies; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000097:blood / Q000235:genetics*; D004777:Environment; D004851:Epoxide Hydrolases / Q000097:blood / Q000235:genetics; D005260:Female; D005714:Gambia; D005838:Genotype; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000097:blood / Q000235:genetics; D006515:Hepatitis B virus; D019694:Hepatitis B, Chronic / Q000097:blood / Q000201:enzymology / Q000235:genetics / Q000652:urine; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000652:urine; D007527:Isoenzymes / Q000097:blood / Q000235:genetics; D008297:Male; D006899:Mixed Function Oxygenases / Q000097:blood / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic; D012621:Seasons; D012709:Serum Albumin / Q000378:metabolism*
D016604:Aflatoxin B1; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System; D004851:Epoxide Hydrolases; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D006854:Hydrocortisone; D007527:Isoenzymes; D006899:Mixed Function Oxygenases; D012709:Serum Albumin; C052669:aflatoxin B1-bovine serum albumin; C001380:6 beta-hydroxycortisol; C104464:CYP3A protein, human; C510163:CYP3A4 protein, human; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human