CORRELATIONS OF CHRONIC HEPATITIS-B VIRUS-INFECTION AND CIGARETTE-SMOKING WITH ELEVATED EXPRESSION OF NEU ONCOPROTEIN IN THE DEVELOPMENT OFHEPATOCELLULAR-CARCINOMA

To investigate the potential role of neu oncogene expression in hepato carcinogenesis, a nested case-control study was conducted within a coh ort of 9691 male adults in Taiwan. Blood samples of study subjects wer e collected during 1984-1986 and frozen at -30 degrees C until subsequ ent analysis. The neu oncoprotein level in the stored serum was measur ed by an enzyme-linked immunosorbent assay for 27 cases of newly devel oped hepatocellular carcinoma (HCC), 12 liver cirrhosis cases, and 40 healthy controls. The mean level of neu oncoprotein was significantly higher in HCC and liver cirrhosis cases than in controls. The risk of HCC increased significantly with increasing serum level of neu oncopro tein (trend test, P = 0.02). The proportion of subjects having an elev ated serum level of neu oncoprotein, defined as a level greater than t he mean level of all controls, was significantly higher among asymptom atic HBsAg carriers than noncarriers (P = 0.05), showing a multivariat e-adjusted odds ratio of 4.0. among HCC cases, a strong association wa s observed between cigarette smoking and elevated prediagnostic serum level of neu oncoprotein. The association remained highly significant (P = 0.017) even when adjustment was made for potential confounders. T he multivariate-adjusted odds ratio of having an elevated serum level of neu oncoprotein, defined as a level greater than the mean plus 1 SD of control levels, for HCC cases who smoked more than 10 cigarettes a day was as high as 386.5 compared with the cases who smoked less than 10 cigarettes a day or nonsmoking cases. The results suggest that bot h HBsAg carrier status and cigarette smoking are related to the increa sed expression of neu oncogene, and cigarette smoking seems to play a significant role in the latter stages of hepatocarcinogenesis. There w as no association between alcohol drinking and serum neu oncoprotein l evel.