Hypermethylation of the RASSF1A gene promoter as the tumor DNA marker for nasopharyngeal carcinoma

Background: RASSF1A is a tumor suppressor gene. The methylation of RASSF1A has been reported to be associated with nasopharyngeal tumorigenesis. However, the heterogeneity was high among different studies. A meta-analysis was performed to evaluate the value of RASSF1A methylation for the diagnosis and early screening of nasopharyngeal carcinoma. Methods: Relevant articles were identified by searching the MEDLINE database. Frequency and odds ratio (OR) were applied to estimate the effect of CDH-1 methylation based on random-/fixed-effect models. The meta-analysis was performed by using MedCalc (R) software. Subgroup analyses were performed by test method, ethnicity, and source of nasopharyngeal carcinoma samples to determine likely sources of heterogeneity. Results: A total of 17 studies, including 1688 samples (1165 nasopharyngeal carcinoma samples, and 523 from non-cancerous samples) were used for the meta-analysis. The overall frequencies of RASSF1A methylation were 59.68% and 2.65% in case-group and control-group, respectively. By removing the poor relative studies, the heterogeneity was not observed among the studies included. The association between RASSF1A gene methylation and the risk of nasopharyngeal carcinoma was also confirmed by calculating the OR value of 30.32 (95%CI = 18.22-50.47) in the fixed-effect model (Q = 16.41, p= 0.36,I-2 = 8.62, 95% CI= 0.00-45.27). Additionally, the significant association was also found between the methylation of the RASSF1A gene and the subgroups. Conclusions: This is the first meta-analysis that has provided scientific evidence that the methylation of RASSF1A is the potential diagnosis, prognosis, and early screening biomarker for nasopharyngeal carcinoma.