Association of FHIT expression and FHIT gene hypermethylation with liver cancer risk: a PRISMA-compliant meta-analysis

BACKGROUND There have been suggestions that fragile histidine triad protein (FHIT) expression and FHIT gene hypermethylation were crucial to the pathogenesis of liver cancer. However, the conclusions remained unclear because of small sample size, disease subtype, and different detection techniques. Therefore, we performed a meta-analysis to estimate the associations of FHIT expression and FHIT gene hypermethylation with liver cancer pathogenesis. METHODS Studies that were published in electronic databases, such as PubMed, Web of Knowledge, China National Knowledge Infrastructure (CNKI), VIP, and WanFang, were retrieved and selected for the meta-analysis. Relative risk (RR) and 95% confidence interval (CI) were calculated to determine the correlations of FHIT expression and FHIT gene hyper-methylation with liver cancer pathogenesis with Stata 12.0 software. RESULTS A total of 17 papers that evaluated the associations of FHIT expression (14 articles) and FHIT gene methylation (3 articles) with liver cancer pathogenesis were included in this meta-analysis. In the overall analysis, the pooled relative risk was 1.93 (95% CI =1.72-2.17), which indicated a significant association between FHIT low expression and liver cancer risk. According to the results of clinical information, there were significant associations of FHIT expression with TNM-stage (RR =2.13, 95% CI =1.72-2.64), tumor size (RR =1.67, 95% CI =1.36-2.05), and merger of cirrhosis (RR =1.34, 95% CI =1.06-1.69) of liver cancer in the Chinese population. In addition, the FHIT gene hypermethylation was significantly associated with the risk of liver cancer (RR =1.45, 95% CI =1.08-1.93). CONCLUSION The FHIT expression and hypermethylation of FHIT gene were significantly associated with the risk of liver cancer, especially in the Chinese population. Furthermore, the results indicated significant associations between FHIT low expression and TNM-stage, tumor size, and merging of cirrhosis of liver cancer in the Chinese population.