Aflatoxin B1 and polycyclic aromatic hydrocarbon adducts, p53 mutations and p16 methylation in liver tissue and plasma of hepatocellular carcinoma patients.
Elevated aflatoxin B(1)-albumin adducts (AFB(1)-Alb) have been associated with an increased risk for HCC development. However, there are no studies in humans, correlating albumin adducts in blood with liver DNA adducts. Forty frozen tumor tissues and 39 paired plasma samples from HCC patients were collected in Taiwan, to determine the relationship between albumin adducts in blood and DNA adducts in liver tissue as well as mutations in p53 and methylation of p16. AFB(1)- and polycyclic aromatic hydrocarbon (PAH)-DNA adducts in tissue and albumin adducts in plasma were determined by immunohistochemistry and competitive ELISA, respectively. Plasma AFB(1)-Alb adducts in subjects with low, medium and high levels of AFB(1)-DNA adducts in tumor tissues were 51.0 +/- 36.5, 70.5 +/- 48.1 and 84.9 +/- 48.2 fmol/mg, respectively (p(trend) = 0.05). No significant correlation was found for PAH. Fourteen of 40 (36%) tissues were positive for mutant p53 protein by immunohistochemistry; 11 of 40 tissue DNA samples (28%) were positive for p53 mutations, but not their corresponding plasma DNAs. p16 was methylated in 24 of 40 (62%) tissues and 12 of 39 (32%) plasma DNAs. Significant correlations were observed between AFB(1)-Alb adducts and p53 mutations and p16 methylation. These data suggest that genetic, epigenetic and environmental exposure biomarkers in plasma may help in estimating the risk for the development of HCC.
Zhang
Yu-Jing
YJ
Department of Environmental Health Science, Mailman School of Public Health of Columbia University, New York, NY 10032, USA. yz6@columbia.edu
Rossner
Pavel
P
Chen
Yu
Y
Agrawal
Meenakshi
M
Wang
Qiao
Q
Wang
Lillian
L
Ahsan
Habibul
H
Yu
Ming-Whei
MW
Lee
Po-Huang
PH
Santella
Regina M
RM
D000328:Adult; D016604:Aflatoxin B1 / Q000032:analysis*; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000737:chemistry* / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D018736:DNA Adducts / Q000032:analysis*; D019175:DNA Methylation; D005260:Female; D019942:Genes, p16; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000737:chemistry; D008113:Liver Neoplasms / Q000097:blood / Q000737:chemistry* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011084:Polycyclic Aromatic Hydrocarbons / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D018736:DNA Adducts; D011084:Polycyclic Aromatic Hydrocarbons; D016159:Tumor Suppressor Protein p53; D016604:Aflatoxin B1