Correlations of chronic hepatitis B virus infection and cigarette smoking with elevated expression of neu oncoprotein in the development of hepatocellular carcinoma.

To investigate the potential role of neu oncogene expression in hepatocarcinogenesis, a nested case-control study was conducted within a cohort of 9691 male adults in Taiwan. Blood samples of study subjects were collected during 1984-1986 and frozen at -30 degrees C until subsequent analysis. The neu oncoprotein level in the stored serum was measured by an enzyme-linked immunosorbent assay for 27 cases of newly developed 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 oncoprotein (trend test, P = 0.02). The proportion of subjects having an elevated serum level of neu oncoprotein, defined as a level greater than the mean level of all controls, was significantly higher among asymptomatic HBsAg carriers than noncarriers (P = 0.05), showing a multivariate-adjusted odds ratio of 4.0. Among HCC cases, a strong association was 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. The 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 both HBsAg carrier status and cigarette smoking are related to the increased expression of neu oncogene, and cigarette smoking seems to play a significant role in the latter stages of hepatocarcinogenesis. There was no association between alcohol drinking and serum neu oncoprotein level.