Hepatitis B and C virus serologies among Japanese Americans with hepatocellular carcinomaNomura AM, Stemmermann GN, Chyou PH, Tabor E
A cohort of 5924 Japanese American men was examined between 1967 and 1970 for hepatocellular carcinoma (HCC). By 1992, 24 incident cases of HCC were histologically confirmed in the group. Frozen serum samples from the 24 men with HCC and 72 age-matched controls were tested for hepatitis B surface antigen (HBsAg), antibodies to hepatitis B core antigen, antibodies to HBsAg, and antibodies to hepatitis C virus. HBsAg was detected in 15 (62.5%) of 24 HCC cases compared with 2 (2.8%) of 72 controls (odds ratio, 43.0; 95% confidence interval, 5.7-325.5). None of the cases and only 1 control had antibody to hepatitis C virus. This study demonstrates a strong association between hepatocellular carcinoma and hepatitis B virus infection, but not with hepatitis C virus infection, among men of Japanese ancestry in Hawaii.
J Infect Dis. 1996 Jun;173(6):1474-6. PMID: 8648223
Mutations of p53 gene in hepatocellular carcinoma: roles of hepatitis B virus and aflatoxin contamination in the dietHsia CC, Kleiner DE Jr, Axiotis CA, Di Bisceglie A, Nomura AM, Stemmermann GN, Tabor E
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.
J Natl Cancer Institute. 1992 Nov 4;84(21):1638-41. PMID: 1279184
Presence of hepatitis B surface antigen before primary hepatocellular carcinomaNomura AM, Stemmermann GN, Wasnich RD.
In a study of 7,498 men of Japanese ancestry in Hawaii, 18 incident cases of primary hepatocellular carcinoma were identified after the follow-up period of 13 years. Sixteen of the 18 patients had stored serum specimens available for analysis. Ten of the 16 had positive serum test results for hepatitis B surface antigen in their original specimens. None of 48 matched controls subjects, whose stored serum specimens were also analyzed, had similar positive test results. This finding indicates that hepatitis B surface antigenemia preceded primary hepatocellular carcinoma in many patients.
JAMA. 1982 Apr 23;247(16):2247-49. PMID: 6279892