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

Yu Jing Zhang, Pavel Rossner, Yu Chen, Meenakshi Agrawal, Qiao Wang, Lillian Wang, Habibul Ahsan, Ming Whei Yu, Po Huang Lee, Regina M. Santella

Research output: Contribution to journalArticle

Abstract

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 AFB 1-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. p!6 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.

Original languageEnglish (US)
Pages (from-to)985-991
Number of pages7
JournalInternational Journal of Cancer
Volume119
Issue number5
DOIs
StatePublished - Sep 1 2006

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Aflatoxin B1
Polycyclic Aromatic Hydrocarbons
Methylation
Hepatocellular Carcinoma
Mutation
Liver
DNA Adducts
Albumins
DNA
Immunohistochemistry
Environmental Exposure
Mutant Proteins
Taiwan
Epigenomics
Neoplasms
Biomarkers
Enzyme-Linked Immunosorbent Assay

Keywords

  • Biomarkers
  • Chemical carcinogens
  • Epigenetics
  • Hepatocarcinogenesis
  • Plasma DNA

ASJC Scopus subject areas

  • Medicine(all)
  • Oncology
  • Cancer Research

Cite this

Aflatoxin B1 and polycyclic aromatic hydrocarbon adducts, p53 mutations and p16 methylation in liver tissue and plasma of hepatocellular carcinoma patients. / Zhang, Yu Jing; Rossner, Pavel; Chen, Yu; Agrawal, Meenakshi; Wang, Qiao; Wang, Lillian; Ahsan, Habibul; Yu, Ming Whei; Lee, Po Huang; Santella, Regina M.

In: International Journal of Cancer, Vol. 119, No. 5, 01.09.2006, p. 985-991.

Research output: Contribution to journalArticle

Zhang, Yu Jing ; Rossner, Pavel ; Chen, Yu ; Agrawal, Meenakshi ; Wang, Qiao ; Wang, Lillian ; Ahsan, Habibul ; Yu, Ming Whei ; Lee, Po Huang ; Santella, Regina M. / Aflatoxin B1 and polycyclic aromatic hydrocarbon adducts, p53 mutations and p16 methylation in liver tissue and plasma of hepatocellular carcinoma patients. In: International Journal of Cancer. 2006 ; Vol. 119, No. 5. pp. 985-991.
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AU - Chen, Yu

AU - Agrawal, Meenakshi

AU - Wang, Qiao

AU - Wang, Lillian

AU - Ahsan, Habibul

AU - Yu, Ming Whei

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AU - Santella, Regina M.

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AB - 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 AFB 1-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. p!6 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.

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