Hepatocellular carcinoma and polymorphisms in carcinogen-metabolizing and DNA repair enzymes in a population with aflatoxin exposure and hepatitis B virus endemicity.

Abstract	High rates of hepatocellular carcinoma (HCC) in The Gambia, West Africa, are primarily due to a high prevalence of chronic hepatitis B virus infection and heavy aflatoxin exposure via groundnut consumption. We investigated genetic polymorphisms in carcinogen-metabolizing (GSTM1, GSTT1, HYL12) and DNA repair (XRCC1) enzymes in a hospital-based case-control study. Incident HCC cases (n = 216) were compared with frequency-matched controls (n = 408) with no clinically apparent liver disease. Although the prevalence of variant genotypes was generally low, in multivariable analysis (adjusting for demographic factors, hepatitis B virus, hepatitis C virus, and TP53 status), the GSTM1-null genotype [odds ratio (OR), 2.45; 95% confidence interval (95% CI), 1.21-4.95] and the heterozygote XRCC1-399 AG genotype (OR, 3.18; 95% CI, 1.35-7.51) were significantly associated with HCC. A weak association of the HYL12 polymorphism with HCC was observed but did not reach statistical significance. GSTT1 was not associated with HCC. The risk for HCC with null GSTM1 was most prominent among those with the highest groundnut consumption (OR, 4.67; 95% CI, 1.45-15.1) and was not evident among those with less than the mean groundnut intake (OR, 0.64; 95% CI, 0.20-2.02). Among participants who had all three suspected aflatoxin-related high-risk genotypes [GSTM1 null, HLY1*2 (HY/HH), and XRCC1 (AG/GG)], a significant 15-fold increased risk of HCC was observed albeit with imprecise estimates (OR, 14.7; 95% CI, 1.27-169). Our findings suggest that genetic modulation of carcinogen metabolism and DNA repair can alter susceptibility to HCC and that these effects may be modified by environmental factors.
Authors	Gregory D Kirk, Paul C Turner, Yunyun Gong, Olufunmilayo A Lesi, Maimuna Mendy, James J Goedert, Andrew J Hall, Hilton Whittle, Pierre Hainaut, Ruggero Montesano, Christopher P Wild
Journal	Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology (Cancer Epidemiol Biomarkers Prev) Vol. 14 Issue 2 Pg. 373-9 (Feb 2005) ISSN: 1055-9965 [Print] United States
PMID	15734960 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Aflatoxins DNA-Binding Proteins X-ray Repair Cross Complementing Protein 1 XRCC1 protein, human glutathione S-transferase T1 Glutathione Transferase glutathione S-transferase M1 Epoxide Hydrolases DNA Repair Enzymes
Topics	Adult Aflatoxins (metabolism, toxicity) Carcinoma, Hepatocellular (chemically induced, enzymology, epidemiology, genetics, virology) DNA Repair Enzymes (genetics, metabolism) DNA-Binding Proteins (genetics) Environmental Exposure (adverse effects) Epoxide Hydrolases (genetics) Female Gambia (epidemiology) Genotype Glutathione Transferase (genetics) Hepatitis B (complications) Humans Liver Neoplasms (chemically induced, enzymology, epidemiology, genetics, virology) Male Middle Aged Polymerase Chain Reaction Polymorphism, Genetic Risk Factors X-ray Repair Cross Complementing Protein 1

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!