Tags

Type your tag names separated by a space and hit enter

p53 mutations, chronic hepatitis B virus infection, and aflatoxin exposure in hepatocellular carcinoma in Taiwan.
Cancer Res. 1997 Aug 15; 57(16):3471-7.CR

Abstract

Recent studies have implicated aflatoxin B1 (AFB1) exposure as an etiological agent in hepatocellular carcinoma (HCC) and suggested an interaction with chronic hepatitis B virus (HBV) infection. Worldwide AFB1 exposure correlates with a specific mutation at codon 249 in the p53 tumor suppressor gene in liver tumors. This study investigated the roles of HBV and AFB1 in the HCC carcinogenic pathway involving p53 mutations. In cases and controls, chronic HBV infection was assessed by serum hepatitis B surface antigen (HBsAg) and AFB1 exposure by immunohistochemical detection of AFB1-DNA adduct in liver tissue. p53 protein mutations in tumor tissues of HCC cases were identified by immunohistochemistry and DNA mutations by single-stranded conformational polymorphism and sequencing analysis. Both chronic HBsAg carrier status and liver AFB1-DNA adducts were significantly higher in cases than in controls with odds ratios (OR) of 8.4 and 3.9, respectively (P < 0.01). Moreover, HCC risk was greatest in individuals with both AFB1-DNA adducts and HBsAg, suggesting a viral-chemical interaction. Mutant p53 protein, mutations in the p53 gene, and specific codon 249 mutations were detected in 37, 29, and 13%, respectively, of the HCC cases. Most of the DNA mutations were transversions, and the only major clustering site for mutations was codon 249. AFB1-DNA adducts were associated with p53 protein (OR = 2.9, P = 0.054) and DNA mutations (OR = 2.9, P = 0.082) but with borderline significance. All of the codon 249 mutations (n = 12) occurred in HBsAg-seropositive carriers, resulting in an OR of 10.0 (P < 0.05), suggesting that HBV may be involved in the selection of these mutations. The ORs between HBsAg and p53 DNA and protein mutations were 2.6 (P = 0.077) and 1.8 (P > 0.05), respectively. Both p53 DNA and protein mutations were related to tumor stage, suggesting that they are late events. These studies provided further support for the role of aflatoxin exposure in HCC in Taiwan and insight into viral-chemical interactions and molecular pathogenesis.

Authors+Show Affiliations

Division of Environmental Health Sciences, Columbia University School of Public Health, New York, New York 10032, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9270015

Citation

Lunn, R M., et al. "P53 Mutations, Chronic Hepatitis B Virus Infection, and Aflatoxin Exposure in Hepatocellular Carcinoma in Taiwan." Cancer Research, vol. 57, no. 16, 1997, pp. 3471-7.
Lunn RM, Zhang YJ, Wang LY, et al. P53 mutations, chronic hepatitis B virus infection, and aflatoxin exposure in hepatocellular carcinoma in Taiwan. Cancer Res. 1997;57(16):3471-7.
Lunn, R. M., Zhang, Y. J., Wang, L. Y., Chen, C. J., Lee, P. H., Lee, C. S., Tsai, W. Y., & Santella, R. M. (1997). P53 mutations, chronic hepatitis B virus infection, and aflatoxin exposure in hepatocellular carcinoma in Taiwan. Cancer Research, 57(16), 3471-7.
Lunn RM, et al. P53 Mutations, Chronic Hepatitis B Virus Infection, and Aflatoxin Exposure in Hepatocellular Carcinoma in Taiwan. Cancer Res. 1997 Aug 15;57(16):3471-7. PubMed PMID: 9270015.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - p53 mutations, chronic hepatitis B virus infection, and aflatoxin exposure in hepatocellular carcinoma in Taiwan. AU - Lunn,R M, AU - Zhang,Y J, AU - Wang,L Y, AU - Chen,C J, AU - Lee,P H, AU - Lee,C S, AU - Tsai,W Y, AU - Santella,R M, PY - 1997/8/15/pubmed PY - 1997/8/15/medline PY - 1997/8/15/entrez SP - 3471 EP - 7 JF - Cancer research JO - Cancer Res. VL - 57 IS - 16 N2 - Recent studies have implicated aflatoxin B1 (AFB1) exposure as an etiological agent in hepatocellular carcinoma (HCC) and suggested an interaction with chronic hepatitis B virus (HBV) infection. Worldwide AFB1 exposure correlates with a specific mutation at codon 249 in the p53 tumor suppressor gene in liver tumors. This study investigated the roles of HBV and AFB1 in the HCC carcinogenic pathway involving p53 mutations. In cases and controls, chronic HBV infection was assessed by serum hepatitis B surface antigen (HBsAg) and AFB1 exposure by immunohistochemical detection of AFB1-DNA adduct in liver tissue. p53 protein mutations in tumor tissues of HCC cases were identified by immunohistochemistry and DNA mutations by single-stranded conformational polymorphism and sequencing analysis. Both chronic HBsAg carrier status and liver AFB1-DNA adducts were significantly higher in cases than in controls with odds ratios (OR) of 8.4 and 3.9, respectively (P < 0.01). Moreover, HCC risk was greatest in individuals with both AFB1-DNA adducts and HBsAg, suggesting a viral-chemical interaction. Mutant p53 protein, mutations in the p53 gene, and specific codon 249 mutations were detected in 37, 29, and 13%, respectively, of the HCC cases. Most of the DNA mutations were transversions, and the only major clustering site for mutations was codon 249. AFB1-DNA adducts were associated with p53 protein (OR = 2.9, P = 0.054) and DNA mutations (OR = 2.9, P = 0.082) but with borderline significance. All of the codon 249 mutations (n = 12) occurred in HBsAg-seropositive carriers, resulting in an OR of 10.0 (P < 0.05), suggesting that HBV may be involved in the selection of these mutations. The ORs between HBsAg and p53 DNA and protein mutations were 2.6 (P = 0.077) and 1.8 (P > 0.05), respectively. Both p53 DNA and protein mutations were related to tumor stage, suggesting that they are late events. These studies provided further support for the role of aflatoxin exposure in HCC in Taiwan and insight into viral-chemical interactions and molecular pathogenesis. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/9270015/p53_mutations_chronic_hepatitis_B_virus_infection_and_aflatoxin_exposure_in_hepatocellular_carcinoma_in_Taiwan_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&amp;pmid=9270015 DB - PRIME DP - Unbound Medicine ER -