It has been reported that the development and progression of gastric cancer are strongly associated with Ras association domain family 1A (RASSF1A) gene methylation; however, some of the findings are contradictory. The aim of this study was to confirm the relationship between RASSF1A methylation and gastric cancer, and the relationship between gender, age, stage, differentiation, pathological type, metastasis of gastric cancer and RASSF1A methylation. We also explored the differences in RASSF1A gene methylation between Asian and non-Asian gastric cancer patients.

Material and methods:
The database was searched for case-control studies of RASSF1A gene methylation associated with gastric cancer, and suitable literature was selected according to pre-defined inclusion and exclusion criteria. The quality of the included literature was evaluated, after which forest plots and funnel plots were performed to analyze sensitivity and publication bias.

A total of 13 papers satisfied the inclusion criteria, and thus were included in this study. Meta-analysis showed that RASSF1A gene methylation was associated with gastric cancer (effect size (ES) = 17.13, 95% confidence interval (CI): 6.94–27.32, p = 0.001; p for heterogeneity = 0.183, I2 = 25.8%). Age (OR = 0.67, 95% CI: 0.47–0.95, p = 0.025; p for heterogeneity = 0.257, I2 = 22.5%), gastric cancer stage (OR = 0.62, 95% CI: 0.44–0.88, p = 0.008; p for heterogeneity = 0.615, I2 = 0%), and gastric cancer metastasis (OR = 2.60, 95% CI: 1.04–6.46, p = 0.040; p for heterogeneity = 0.904, I2 = 0%) were associated with RASSF1A gene methylation. Gender (OR = 1.16, 95% CI: 0.84–1.62, p = 0.369; p for heterogeneity = 0.704, I2 = 0%), degree of gastric cancer differentiation (OR = 0.96, 95% CI: 0.60–1.52, p = 0.860; p for heterogeneity = 0.077, I2 = 47.3%), and pathological type of gastric cancer (OR = 1.15, 95% CI: 0.64–2.09, p = 0.635; p for heterogeneity = 0.276, I2 = 22.5%) were not associated with methylation of the RASSF1A gene. No significant publication bias was found in this study.

Gastric carcinogenesis was found to be associated with RASSF1A gene methylation. There were no significant differences in RASSF1A gene methylation among patients of different ages, different stages, and metastasis of gastric cancer. Yet, there were significant differences in RASSF1A gene methylation in patients of different gender, degree of gastric cancer differentiation, and type of gastric cancer pathology.

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