Genetic polymorphism in DNMTs and gastric cancer: A systematic review and meta-analysis

Single nucleotide polymorphisms (SNPs) in DNA methyltransferases (DNMTs) modulate protein expression and affect DNA methylation.Aberrant DNA methylation, have been associated with gastric carcinogenesis.DNMT2 rs11254413 is associated with protection for GC development.DNMT3A rs7560488, DNMT3A rs36012910 and, specially, DNMT1 rs16999593 are associated with increased susceptibility for GC development.

Epigenetics alterations, including aberrant DNA methylation, have been associated with gastric carcinogenesis. Single nucleotide polymorphisms (SNPs) in DNA methyltransferases (DNMTs) may influence protein expression and therefore affect DNA regulation and susceptibility for Gastric Cancer (GC).We have performed a systematic review and meta-analysis involving 11 studies and a total of 24 SNPs in DNMTs were analyzed. According to literature, only 4 SNPs, DNMT1 rs16999593, DNMT2 rs11254413 and DNMT3A rs7560488 and DNMT3A rs36012910, were associated with GC. DNMT1 rs16999593 and DNMT3A rs7560488C allele and DNMT3A rs36012910 G allele showed an increased risk for GC. On the other hand, DNMT2 rs11254413 G allele presented a protective effect for GC. Additionally, the meta-analysis evaluated the SNPs analyzed in more than one study (n = 6). Results revealed that only DNMT1 rs16999593 had a statistically significant association with GC development (OR = 1.31; 95% CI = 1.08-1.60; p = 0.006 for TC + CC genotypes).Our study suggests that DNMT2 rs11254413, DNMT3A rs7560488, DNMT3A rs36012910 and, specially, DNMT1 rs16999593 may have an association with GC development. Nevertheless, further studies are need using different populations to clarify this association with GC risk.