C rs2288349 G N A rs721186 G N A rs13784 G N A rs11488 A N T rs36012910 A N G rs13428812 A N G rs11887120 T N C rs7560488 T N C rs6119954 G N A rs4911107 A N G rs4911259 G N T rs8118663 A N G rs2424908 T N C rs6087990 C N T 1.16 (0.81, 1.68) 0.96 (0.66, 1.41) 1.08 (0.88, 1.43) 0.93 (0.71, 1.22) 1.12 (0.06, 16.0) ??2.44 (1.37, 4.33) 0.93 (0.64, 1.35) 0.96 (0.63, 1.47) 1.73 (1.24, 2.41) 1.00 (0.76, 1.31) 0.86 (0.26, 2.88) 0.86 (0.26, 2.89) 1.28 (0.95, 1.72) 0.98 (0.66, 1.45) ?Homozygote model 0.62 (0.30, 1.27) 1.17 (1.88,1.55) 1.18 (0.82, 1.69) 0.81 (0.50, 1.33) ???1.00 (0.98, 1.01) 1.11 (0.58, 2.12) 1.26 (0.76, 2.07) 2.50 (1.01, 6.23) 1.37 (0.88, 2.13) 0.76 (0.23, 2.46) 0.76 (0.23, 2.45) 1.32 (0.91, 1.91) 1.05 (0.64, 1.71) 1.46 (1.07, 2.01)SNPs, single nucleotide polymorphisms; heterozygote model (heterozygous vs. homozygous frequent allele); homozygote model (homozygous rare vs. homozygous frequent allele). The bolds pointed to SNPs that had statistically significant associations with gastric cancer.prognosis in GC cases (Wang et al., 2015a). Maybe it played different roles in pathogenesis and prognosis. Particularly, we found in Jiangsu, a high GC incidence area of China (Liu et al., 2007), mutant rs1550117 doubled the risk and mutant rs1569686 lowered by a half of it. Also, even though some studies discovered TaqMan was more specific andsensitive than PCR-RFLP to detect polymorphisms or virus (Martinez-Trevino et al., 2016; Campsall et al., 2004), we found PCRRFLP was so far a best method for risk detection in GC. Regarding rs2424913, we didn’t find it associated with GC in Chinese. A review reported it could significantly decrease cancers in African but not AsianFig. 3. Forest plot of subgroup analysis on DNMT3A rs1550117 and DNMT3B rs1569686 polymorphisms (dominant model) by population area and genetic methods. Population area (Jiangsu ICG-001 biological activity province and other provinces: Jiangxi, Jilin and Heilong Jiang provinces, in China) (A); Genetic methods (PCR-RFLP and other methods: TaqMan and MassArray) (B).H. Li et al. / EBioMedicine 13 (2016) 125?(Duan et al., 2015). It was speculated whether rs2424913 enabled African to catch GC rather than other populations. Although some metaanalysis studies demonstrated that rs6087990 might confer protection against overall cancers (Duan et al., 2015; Zhang et al., 2015), but it represented an opposite effect on GC as our systematic review showed (Liu, 2008). 4.3. Strengths and Limitations Previous meta-analysis studies primarily evaluated associations between a few SNPs and cancers without classification, such as GC (Zhu et al., 2015; Duan et al., 2015; Liu et al., 2015; Zhang et al., 2015; Xia et al., 2015). The major strengths of our study was its comprehensive and systematic focus on GC and SNPs from three main types of DNMTs, 17 SNPs in total. Also, some mistakes in previous buy STI-571 results were corrected in our study (Liu et al., 2015). At the same time, there were some limitations. Firstly, significant heterogeneities were observed for a few genetic models. Although a sensitivity analysis and a subgroup analysis were performed to clarify sources, we cannot find all potential factors. Second the meta-analysis findings were currently restricted to Chinese population pending results from other populations in future studies. 5. Conclusion Our meta-analysis suggested that DNMT1 rs16999593 and DNMT3A rs1550117 could contribute to GC and that DNMT3B rs1569686 might function as a protective factor against gastric ca.C rs2288349 G N A rs721186 G N A rs13784 G N A rs11488 A N T rs36012910 A N G rs13428812 A N G rs11887120 T N C rs7560488 T N C rs6119954 G N A rs4911107 A N G rs4911259 G N T rs8118663 A N G rs2424908 T N C rs6087990 C N T 1.16 (0.81, 1.68) 0.96 (0.66, 1.41) 1.08 (0.88, 1.43) 0.93 (0.71, 1.22) 1.12 (0.06, 16.0) ??2.44 (1.37, 4.33) 0.93 (0.64, 1.35) 0.96 (0.63, 1.47) 1.73 (1.24, 2.41) 1.00 (0.76, 1.31) 0.86 (0.26, 2.88) 0.86 (0.26, 2.89) 1.28 (0.95, 1.72) 0.98 (0.66, 1.45) ?Homozygote model 0.62 (0.30, 1.27) 1.17 (1.88,1.55) 1.18 (0.82, 1.69) 0.81 (0.50, 1.33) ???1.00 (0.98, 1.01) 1.11 (0.58, 2.12) 1.26 (0.76, 2.07) 2.50 (1.01, 6.23) 1.37 (0.88, 2.13) 0.76 (0.23, 2.46) 0.76 (0.23, 2.45) 1.32 (0.91, 1.91) 1.05 (0.64, 1.71) 1.46 (1.07, 2.01)SNPs, single nucleotide polymorphisms; heterozygote model (heterozygous vs. homozygous frequent allele); homozygote model (homozygous rare vs. homozygous frequent allele). The bolds pointed to SNPs that had statistically significant associations with gastric cancer.prognosis in GC cases (Wang et al., 2015a). Maybe it played different roles in pathogenesis and prognosis. Particularly, we found in Jiangsu, a high GC incidence area of China (Liu et al., 2007), mutant rs1550117 doubled the risk and mutant rs1569686 lowered by a half of it. Also, even though some studies discovered TaqMan was more specific andsensitive than PCR-RFLP to detect polymorphisms or virus (Martinez-Trevino et al., 2016; Campsall et al., 2004), we found PCRRFLP was so far a best method for risk detection in GC. Regarding rs2424913, we didn’t find it associated with GC in Chinese. A review reported it could significantly decrease cancers in African but not AsianFig. 3. Forest plot of subgroup analysis on DNMT3A rs1550117 and DNMT3B rs1569686 polymorphisms (dominant model) by population area and genetic methods. Population area (Jiangsu province and other provinces: Jiangxi, Jilin and Heilong Jiang provinces, in China) (A); Genetic methods (PCR-RFLP and other methods: TaqMan and MassArray) (B).H. Li et al. / EBioMedicine 13 (2016) 125?(Duan et al., 2015). It was speculated whether rs2424913 enabled African to catch GC rather than other populations. Although some metaanalysis studies demonstrated that rs6087990 might confer protection against overall cancers (Duan et al., 2015; Zhang et al., 2015), but it represented an opposite effect on GC as our systematic review showed (Liu, 2008). 4.3. Strengths and Limitations Previous meta-analysis studies primarily evaluated associations between a few SNPs and cancers without classification, such as GC (Zhu et al., 2015; Duan et al., 2015; Liu et al., 2015; Zhang et al., 2015; Xia et al., 2015). The major strengths of our study was its comprehensive and systematic focus on GC and SNPs from three main types of DNMTs, 17 SNPs in total. Also, some mistakes in previous results were corrected in our study (Liu et al., 2015). At the same time, there were some limitations. Firstly, significant heterogeneities were observed for a few genetic models. Although a sensitivity analysis and a subgroup analysis were performed to clarify sources, we cannot find all potential factors. Second the meta-analysis findings were currently restricted to Chinese population pending results from other populations in future studies. 5. Conclusion Our meta-analysis suggested that DNMT1 rs16999593 and DNMT3A rs1550117 could contribute to GC and that DNMT3B rs1569686 might function as a protective factor against gastric ca.
