Abstract
BackgroundRunt-related transcription factor 3 (RUNX3) is a member of the runt-domain family of transcription factors and has been reported to be a candidate tumor suppressor in gastric cancer. However, the association between RUNX3 promoter methylation and gastric cancer remains unclear.MethodsWe systematically reviewed studies of RUNX3 promoter methylation and gastric cancer published in English or Chinese from January 2000 to January 2011, and quantified the association between RUNX3 promoter methylation and gastric cancer using meta-analysis methods.ResultsA total of 1740 samples in 974 participants from seventeen studies were included in the meta-analysis. A significant association was observed between RUNX3 promoter methylation and gastric cancer, with an aggregated odds ratio (OR) of 5.63 (95%CI 3.15, 10.07). There was obvious heterogeneity among studies. Subgroup analyses (including by tissue origin, country and age), meta-regression were performed to determine the source of the heterogeneity. Meta-regression showed that the trend in ORs was inversely correlated with age. No publication bias was detected. The ORs for RUNX3 methylation in well-differentiated vs undifferentiated gastric cancers, and in intestinal-type vs diffuse-type carcinomas were 0.59 (95%CI: 0.30, 1.16) and 2.62 (95%CI: 1.33, 5.14), respectively. There were no significant differences in RUNX3 methylation in cancer tissues in relation to age, gender, TNM stage, invasion of tumors into blood vessel or lymphatic ducts, or tumor stage.ConclusionsThis meta-analysis identified a strong association between methylation of the RUNX3 promoter and gastric cancer, confirming the role of RUNX3 as a tumor suppressor gene.
Highlights
Runt-related transcription factor 3 (RUNX3) is a member of the runt-domain family of transcription factors and has been reported to be a candidate tumor suppressor in gastric cancer
The remaining 17 studies included data on the relationship between RUNX3 gene promoter methylation and gastric cancer, and these studies were pooled for analysis (Table 1) [14,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41]
We found that the odds ratio (OR) for RUNX3 methylation decreased from 15.00 in the younger age group, through 6.31, to 3.75 in the oldest age group
Summary
Runt-related transcription factor 3 (RUNX3) is a member of the runt-domain family of transcription factors and has been reported to be a candidate tumor suppressor in gastric cancer. The association between RUNX3 promoter methylation and gastric cancer remains unclear. RUNX3 is a known regulator of major developmental pathways, and has recently been reported as a candidate tumor suppressor [3,4,5]. The role of RUNX3 in the regulation of gastric epithelial cell growth and its tumor suppressor activity in gastric cancer remain to be clarified. Carvalho et al refuted a tumor suppressor role for the RUNX3 gene in early-onset gastric carcinomas, on the basis of its lack of expression in histological nonneoplastic gastric epithelium, at least two copies of the gene were present in the vast majority of cells analyzed [22]. Associations between RUNX3 promoter methylation and gastric cancer have mostly been investigated in studies with small sample sizes, low statistical power, specific ethnic backgrounds, or other limitations in study design, leading to conflicting results
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
