Aflatoxin B1 and polycyclic aromatic hydrocarbon adducts, p53 mutations and p16 methylation in liver tissue and plasma of hepatocellular carcinoma patients

• Published in: International journal of cancer Vol. 119; no. 5; pp. 985 - 991
• Main Authors: Zhang, Yu‐Jing, Rossner, Pavel, Chen, Yu, Agrawal, Meenakshi, Wang, Qiao, Wang, Lillian, Ahsan, Habibul, Yu, Ming‐Whei, Lee, Po‐Huang, Santella, Regina M.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.09.2006; Wiley-Liss
• Subjects: Adult; Aflatoxin B1 - analysis; Aged; bio markers; Biological and medical sciences; Biomarkers, Tumor - analysis; Carcinoma, Hepatocellular - blood; Carcinoma, Hepatocellular - chemistry; Carcinoma, Hepatocellular - genetics; chemical carcinogens; Cyclin-Dependent Kinase Inhibitor p16 - genetics; DNA Adducts - analysis; DNA Methylation; epigenetics; Female; Gastroenterology. Liver. Pancreas. Abdomen; Genes, p16; Genes, p53; hepatocarcinogenesis; Humans; Immunohistochemistry; Liver - chemistry; Liver Neoplasms - blood; Liver Neoplasms - chemistry; Liver Neoplasms - genetics; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Middle Aged; Mutation; plasma DNA; Polycyclic Aromatic Hydrocarbons - metabolism; Tumor Suppressor Protein p53 - genetics; Tumors; Biological marker; Hepatic disease; Hepatocellular carcinoma; hepatocarcinogenesis; Carcinogenesis; CDKN2 gene; Blood plasma; Liver cancer; Cancerology; TP53 Gene; Genetics; Molecular adduct; Tumor suppressor gene; Human; biomarkers; Malignant tumor; Polycyclic aromatic compound; Toxin; Carcinogen; chemical carcinogens; Aflatoxin B1; Epigenetics; Digestive diseases; Mutation; Methylation; plasma DNA
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.21699

Elevated aflatoxin B1‐albumin adducts (AFB1‐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. AFB1‐ and polycyclic aromatic hydrocarbon (PAH)‐DNA adducts in tissue and albumin adducts in plasma were determined by immunohistochemistry and competitive ELISA, respectively. Plasma AFB1‐Alb adducts in subjects with low, medium and high levels of AFB1‐DNA adducts in tumor tissues were 51.0 ± 36.5, 70.5 ± 48.1 and 84.9 ± 48.2 fmol/mg, respectively (ptrend = 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 AFB1‐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. © 2006 Wiley‐Liss, Inc.