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Mutations of p53 gene in hepatocellular carcinoma: roles of hepatitis B virus and aflatoxin contamination in the diet.
J Natl Cancer Inst. 1992 Nov 04; 84(21):1638-41.JNCI

Abstract

BACKGROUND

Mutations of the p53 tumor suppressor gene have been reported in 50% of patients with hepatocellular carcinoma (HCC) from China and South Africa. These reports suggested an association of p53 mutations with high levels of aflatoxin in the diet. Most studies of p53 and HCC, however, have not fully evaluated the possible role of the hepatitis B virus (HBV). Aflatoxin is a substance produced by food mold that is known to cause HCC in experimental animals.

PURPOSE

The purpose of this study was to evaluate the relationship of p53 gene mutation to high or low levels of aflatoxin in the diet and to HBV infection.

METHODS

p53 protein and hepatitis B surface antigen (HBsAg) were evaluated by immunohistochemistry using the avidin-biotin-peroxidase system in paraffin-embedded specimens of HCC and of adjacent nontumorous liver tissue from 43 patients. Tissue specimens from three normal human livers were also evaluated. HCCs and adjacent nontumorous liver tissues were obtained from 23 patients from Qidong, China, where aflatoxin levels in the diet are high, and from 20 patients from two regions in the United States (patients from the National Institutes of Health, Bethesda, Md., and Kuakini Medical Center, Honolulu, Hawaii), where aflatoxin levels in the diet are low.

RESULTS

Mutant p53 protein was detected in the nuclei of HCCs from 14 (61%) of 23 patients from China and from three (30%) of 10 patients and six (60%) of 10 patients, respectively, from the two regions of the United States. A statistically significant association between detection of mutant p53 protein in HCC cells and the detection of HBsAg in hepatocytes of the adjacent nontumorous liver tissue was observed in patients from China and the United States considered together.

CONCLUSION

Mutations of the tumor suppressor gene p53 in hepatocellular carcinomas are not limited to patients from geographic regions where the ingestion of aflatoxin is high. In many patients, these mutations may be associated with HBV infection.

IMPLICATIONS

The possible interaction of chronic HBV infection and p53 gene mutation, suggested by these data, indicates a mechanism by which HBV infection beginning early in life could contribute to the subsequent development of HCC.

Authors+Show Affiliations

Division of Cancer Etiology, National Cancer Institute, National Institutes of Health, Bethesda, Md 20892.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

1279184

Citation

Hsia, C C., et al. "Mutations of P53 Gene in Hepatocellular Carcinoma: Roles of Hepatitis B Virus and Aflatoxin Contamination in the Diet." Journal of the National Cancer Institute, vol. 84, no. 21, 1992, pp. 1638-41.
Hsia CC, Kleiner DE, Axiotis CA, et al. Mutations of p53 gene in hepatocellular carcinoma: roles of hepatitis B virus and aflatoxin contamination in the diet. J Natl Cancer Inst. 1992;84(21):1638-41.
Hsia, C. C., Kleiner, D. E., Axiotis, C. A., Di Bisceglie, A., Nomura, A. M., Stemmermann, G. N., & Tabor, E. (1992). Mutations of p53 gene in hepatocellular carcinoma: roles of hepatitis B virus and aflatoxin contamination in the diet. Journal of the National Cancer Institute, 84(21), 1638-41.
Hsia CC, et al. Mutations of P53 Gene in Hepatocellular Carcinoma: Roles of Hepatitis B Virus and Aflatoxin Contamination in the Diet. J Natl Cancer Inst. 1992 Nov 4;84(21):1638-41. PubMed PMID: 1279184.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mutations of p53 gene in hepatocellular carcinoma: roles of hepatitis B virus and aflatoxin contamination in the diet. AU - Hsia,C C, AU - Kleiner,D E,Jr AU - Axiotis,C A, AU - Di Bisceglie,A, AU - Nomura,A M, AU - Stemmermann,G N, AU - Tabor,E, PY - 1992/11/14/pubmed PY - 2001/3/28/medline PY - 1992/11/14/entrez SP - 1638 EP - 41 JF - Journal of the National Cancer Institute JO - J. Natl. Cancer Inst. VL - 84 IS - 21 N2 - BACKGROUND: Mutations of the p53 tumor suppressor gene have been reported in 50% of patients with hepatocellular carcinoma (HCC) from China and South Africa. These reports suggested an association of p53 mutations with high levels of aflatoxin in the diet. Most studies of p53 and HCC, however, have not fully evaluated the possible role of the hepatitis B virus (HBV). Aflatoxin is a substance produced by food mold that is known to cause HCC in experimental animals. PURPOSE: The purpose of this study was to evaluate the relationship of p53 gene mutation to high or low levels of aflatoxin in the diet and to HBV infection. METHODS: p53 protein and hepatitis B surface antigen (HBsAg) were evaluated by immunohistochemistry using the avidin-biotin-peroxidase system in paraffin-embedded specimens of HCC and of adjacent nontumorous liver tissue from 43 patients. Tissue specimens from three normal human livers were also evaluated. HCCs and adjacent nontumorous liver tissues were obtained from 23 patients from Qidong, China, where aflatoxin levels in the diet are high, and from 20 patients from two regions in the United States (patients from the National Institutes of Health, Bethesda, Md., and Kuakini Medical Center, Honolulu, Hawaii), where aflatoxin levels in the diet are low. RESULTS: Mutant p53 protein was detected in the nuclei of HCCs from 14 (61%) of 23 patients from China and from three (30%) of 10 patients and six (60%) of 10 patients, respectively, from the two regions of the United States. A statistically significant association between detection of mutant p53 protein in HCC cells and the detection of HBsAg in hepatocytes of the adjacent nontumorous liver tissue was observed in patients from China and the United States considered together. CONCLUSION: Mutations of the tumor suppressor gene p53 in hepatocellular carcinomas are not limited to patients from geographic regions where the ingestion of aflatoxin is high. In many patients, these mutations may be associated with HBV infection. IMPLICATIONS: The possible interaction of chronic HBV infection and p53 gene mutation, suggested by these data, indicates a mechanism by which HBV infection beginning early in life could contribute to the subsequent development of HCC. SN - 0027-8874 UR - https://www.unboundmedicine.com/medline/citation/1279184/Mutations_of_p53_gene_in_hepatocellular_carcinoma:_roles_of_hepatitis_B_virus_and_aflatoxin_contamination_in_the_diet_ L2 - https://academic.oup.com/jnci/article-lookup/doi/10.1093/jnci/84.21.1638 DB - PRIME DP - Unbound Medicine ER -