Abstract
BackgroundIncreasing studies showed that abnormal changes in single nucleotide polymorphisms (SNPs) of DNMTs (DNMT1, DNMT3A and DNMT3B) were associated with occurrence or decrease of various tumors. However, the associations between DNMTs variations and gastric cancer (GC) risk were still conflicting. We aimed to assess the effect of DNMTs polymorphisms on the susceptibility to GC. MethodsFirstly, we did a meta-analysis for 7 SNPs (rs16999593, rs2228611, rs8101866 in DNMT1, rs1550117, rs13420827 in DNMT3A, rs1569686, rs2424913 in DNMT3B). Four genetic models (homozygote, heterozygote, dominant and recessive model) were used. Moreover, a meta-sensitivity and subgroup analysis was performed to clarify heterogeneity source. Lastly, 17 SNPs that couldn't be meta-analyzed were presented in a systematic review. Findings20 studies were included, 13 studies could be meta-analyzed and 7 ones could not. Firstly, a meta-analysis on 13 studies (3959 GC cases and 5992 controls) for 7 SNPs showed that GC risk increased in rs16999593 (heterozygote model: OR 1.36, 95%CI 1.14–1.61; dominant model: OR 1.36, 95%CI 1.15–1.60) and rs1550117 (homozygote model: OR 2.03, 95%CI 1.38–3.00; dominant model: OR 1.20, 95%CI 1.01–1.42; recessive model: OR 1.96, 95%CI 1.33–2.89) but decreased in rs1569686 (dominant model: OR 0.74, 95%CI 0.61–0.90). The remaining SNPs were not found associated with GC risk. Furthermore, the subgroup analysis indicated that for rs1550117 and rs1569686, the significant associations were particularly found in people from Chinese Jiangsu province (rs1550117, OR 1.77, 95%CI 1.25–2.51; rs1569686, OR 0.48, 95%CI 0.36–0.64) and that PCR-RFLP was a sensitive method to discover significant associations (rs1550117, OR 1.77, 95%CI 1.25–2.51; rs1569686, OR 0.49, 95%CI 0.37–0.65). Lastly, a systematic review on 7 studies for 17 SNPs suggested that rs36012910, rs7560488 and rs6087990 might have a potential effect on GC initiation. ConclusionThis meta-analysis demonstrated that rs16999593 and rs1550117 could contribute to GC risk and that rs1569686 might be a protective factor against gastric carcinogenesis. By using these SNPs as biomarkers, it is feasible to estimate the risk of acquiring GC and thus formulate timely preventive strategy.
Highlights
In 2012, 951,000 new gastric cancer (GC) cases and 723,000 deaths were estimated worldwide, making it the fifth most common tumor (Ferlay et al, 2015; Torre et al, 2015)
DNMT3A and DNMT3B are considered as de novo methyltransferases which are required for the establishment of embryonic methylation patterns, mainly occurring during gametogenesis and early development (Okano et al, 1999) and they are encoded by DNMT3A and DNMT3B genes locating on chromosome 2p23 and 20q11.2 respectively (Yang et al, 2012)
In those 249 publications were excluded because 5 were meta-analysis and the other 244 were not related to DNMTs single nucleotide polymorphisms (SNPs) and GC risk
Summary
In 2012, 951,000 new gastric cancer (GC) cases and 723,000 deaths were estimated worldwide, making it the fifth most common tumor (Ferlay et al, 2015; Torre et al, 2015). A meta-analysis on 13 studies (3959 GC cases and 5992 controls) for 7 SNPs showed that GC risk increased in rs16999593 (heterozygote model: OR 1.36, 95%CI 1.14–1.61; dominant model: OR 1.36, 95%CI 1.15–1.60) and rs1550117 (homozygote model: OR 2.03, 95%CI 1.38–3.00; dominant model: OR 1.20, 95%CI 1.01–1.42; recessive model: OR 1.96, 95%CI 1.33–2.89) but decreased in rs1569686 (dominant model: OR 0.74, 95%CI 0.61–0.90). Conclusion: This meta-analysis demonstrated that rs16999593 and rs1550117 could contribute to GC risk and that rs1569686 might be a protective factor against gastric carcinogenesis. By using these SNPs as biomarkers, it is feasible to estimate the risk of acquiring GC and formulate timely preventive strategy
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