p53 Mutation at Serine 249 and Its Gain of Function Are Highly Related to Hepatocellular Carcinoma after Smoking Exposure

Background: It has been convincingly suggested that a close correlation exists between the incidence of hepatocellular carcinoma (HCC) and cigarette smoking. However, the underlying effect of smoking on HCC is not clear. Methods: A binary unconditional logistic regression was used for the data on a total of 300 cases and 612 controls. The approach of functional analysis of separated alleles in yeast and direct sequencing of TP53 mutations were applied to analyze the p53 status in the HCC group. The relationship between p53 mutation at serine 249 (p53-RS) and smoking was assessed. Quantitative reverse transcription PCR was employed for the evaluation to transcriptional activity of p53 and p53-RS. Results: Smoking was linked to the risk of HCC with an increased dose-response effect. Moreover, among subjects who did not drink, the risks of HCC were significantly increased for smokers between HCC and controls. Besides, there was an increase in the number of HCC in smokers compared to nonsmokers after exclusion of HBV and/or HCV infection. Also, a significant difference was observed in the incidence of p53-RS between smokers and nonsmokers the HCC group. Furthermore, the p53-RS transcriptional activity was significantly increased in tumor tissues. Conclusions: It strongly demonstrated that tobacco smoking is positively and independently associated with HCC, which may be attributed to p53-RS and its gain of function.