CpG Island Methylator Phenotype Involving Tumor Suppressor Genes Located On Chromosome3p In Gastric Cancer

Objective: To assess the association of RASSF1A promoter methylation with gastric cancer risk by acomprehensive meta-analysis. Methods: Relevant studies were identified by searches of PubMed andWeb of Science databases with no restrictions. Combined odds ratio (OR) and95%confidence interval(CI) were used to assess the strength of the association between RASSF1A promoter methylation andgastric cancer risk. A chi-square-based Q-test and sensitivity analyses were performed to test thebetween-study heterogeneity and the contributions of single studies to the final results, respectively.Funnel plots were carried out to evaluate publication bias. Results: Overall, a significant associationwas observed between RASSF1A promoter methylation and gastric cancer risk (OR,12.67;95%CI,8.12-19.78; P <0.001) with no between-study heterogeneity. Subgroup analyses further revealed thatgastric cancer risk was increased for individuals carrying the methylated RASSF1A compared withthose with unmethylated RASSF1A. In addition, no publication bias was detected in the overall andsubgroup analyses. Conclusion: This sudy identified a strong association between RASSF1A promotermethylation and risk of gastric cancer, and highlighted a promising potential for RASSF1A promotermethylation in gastric cancer risk prediction. Objective: To study whether CpG island methylation phenotype (CIMP) status involving tumorsuppressor gene lacated on chromosome3p could correlate with gastric cancer. Methods: Methylationspecific PCR (MSP) was used to examine methylation profiles for eight TSGs harbored in chromosome3p in100gastric cancer tissues and100paired normal tissues. CIMP positive is referred to having fouror more than four synchronously methylated genes per sample. The correlation of CIMP and the overallsurvival time were evaluated by Kaplan-Meier chart and Log-rank test．Cox model was used formultivariate analysis．Results:99of100(99%) gastric cancer tissue samples presented promotermethylation of at least one gene. The frequency of promoter methylation for eight genes explored ranged from7%for hOGG1to67%for FHIT. CIMP+increased in44of100gastric cancer tissues(44.0%) as compared to the paired normal tissues (4.0%), respectively (P<0.001). CIMP positive isclosely related to the low degree of tumor differentiation (P=0.004) and lymph node metastasis(P=0.005). The median survival time of patients with negative and positive CIMP was31and15months，respectively (P=0.009). Cox regression analysis suggested that CIMP was independent factorsaffecting the prognosis of gastric cancer patients (OR,4.3063;95%CI,1.7158-10.8084; P=0.002).Conclusion: Normal and malignant gastric tissues are found to have its own unique CIMP patterns.CIMP+may play a role in poor differentiation and lymph node metastasis of gastric cancer and could beused as an important survival predictor in human gastric cancer. Objective: To assess the association of CpG island methylator phenotype status involving tumorsuppressor genes located on chromosome3p with gastric cancer risk by a case-control study. Methods:Using MSP method, we examined methylation profiles for eight TSGs harbored in chromosome3p in100gastric cancer blood samples as well as70normal blood samples. Odds ratio (OR) and95%confidence interval (CI) were used to assess the strength of the association between CIMP and gastriccancer risk. Results:99/100(99%) gastric cancer blood samples presented promoter methylation of atleast one gene. Given that VHL and hOGG1showed no methylation of any sample, we didn‘t considerthe contribution of the two gene to CIMP+. CIMP+was found in30.0%(30/100) of blood samples fromgastric cancer patients and4.3%(3/70) of normal blood samples, respectively (P<0.001). CIMP+isclosely related to the low degree of tumor differentiation (P=0.019) and lymph node metastasis(P=0.032). A significant association was observed between CIMP and gastric cancer risk (OR,9.53;95%CI,2.63-30.83; P<0.001). Conclusion: CIMP in peripheral blood cells could provide usefulbiomarkers of susceptibility to gastric cancer.