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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 hypermethylation 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 metaanalysis. 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. [ABSTRACT FROM AUTHOR]

Objective: Previous studies have reported that Ras-associated domain family 1A (RASSF1A), the most commonly silenced tumor suppressor via promoter methylation, played vital roles in the development of carcinogenesis. The purpose of this meta-analysis was to determine whether RASSF1A promoter methylation increased the risk of thyroid cancer. Methods: PubMed, Embase, ISI Web of Knowledge, and Chinese National Knowledge Infrastructure databases were searched to obtain eligible studies. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the strength of the associations, using Stata 12.0 software. The methodological quality of included studies was evaluated using Newcastle-Ottawa scale table. Egger's test and Begg's test were applied to detect publication biases. TSA 0.9 software was used to calculate the required information size and whether the result was conclusive. Results: A total of 10 articles with 12 studies that included 422 thyroid cancer patients, identifying the association of RASSF1A promoter methylation with thyroid cancer risk, were collected in this meta-analysis. Overall, RASSF1A promoter methylation significantly increased the risk of thyroid cancer (total, OR=8.27, CI=4.38-15.62, P<0.05; Caucasian, OR=9.25, CI=3.97-21.56, P<0.05; Asian, OR=7.01, CI=2.68-18.38, P<0.05). In the subgroup analysis based on sample type, a significant association between thyroid cancer group and control group was found (normal tissue, OR=9.55, CI=4.21-21.67, P<0.05; adjacent tissue, OR=6.80, CI=2.49-18.56, P<0.05). The frequency of RASSF1A promoter methylation in follicular thyroid carcinoma was higher than in control group (OR=11.88, CI=5.80-24.32, P<0.05). In addition, the results indicated that the RASSF1A promoter methylation was correlated with papillary thyroid carcinoma in Caucasians and Asians (total, OR=8.07, CI=3.54-18.41, P<0.05; Caucasian, OR=11.35, CI=2.39-53.98, P<0.05; Asian, OR=6.67, CI=2.53-17.64, P<0.05). On the basis of the trial sequential analysis, the significant association of RASSF1A promoter methylation with thyroid cancer risk was found, and there was no need to perform further studies. Conclusion: This meta-analysis confirms that RASSF1A promoter methylation is a risk factor for thyroid tumor. [ABSTRACT FROM AUTHOR]