| Cancer is a medical problem that human beings must overcome in the future.Due to the late start of economic development in China,most people are living a low standard life under the heavily pressure from life and work.As a result,people’s health awareness is generally weak,and prevention awareness and attention to major diseases such as cancer are not high enough.Both lung cancer and gastric cancer are cancer types with very high rates of domestic and mortality.The tumor is already in the advanced stage when most patients diagnosed with lung or gastric cancer,by which time there is lack of effective means to treat it,and the 5-year survival rate is very low.Therefore,it is necessary to find effective markers for early screening and prevention of lung and gastric cancer.Epigenetic regulation has been a hot topic in the field of cancer research in recent years.DNA methylation,as one of the classical epigenetic regulation methods,plays an important role in tumorgenesis.DNA methylation is catalyzed by DNA methytransferases(DNMTs),and DNA methylation pattern is typically established by de nove DNMT3A/3B and maintenanced by DNMT1.Previous studies have revealed that some single nucleotide polymorphisms of DNMT3 A and DNMT3 B were associated with cancers,but no research reported the association between promoter SNPs,rs1550117 of DNMT3 A and rs2424913 and rs1569686 of DNMT3 B,and the risk of lung cancer and gastric cancer.Thus,we conducted a hospital based case-control study of 1798 normal people,600 non-small-cell lung cancer patients,550 lung cancer patients and 460 gastric cancer patients,using PCR-RFLP method and DNA sequencing to investigate the statistically association between rs1550117,rs2424913 and rs1569686 and the risk of lung cancer and gastric cancer.Our results showed that DNMT3 A rs1550117 G allele was significantly associated with increased risk of non-small-cell cancer(G vs A,P=0.001,OR=1.36,95%CI=1.18-1.71;GG vs GA,P=0.010,OR=1.33,95%CI=1.06-1.71;GG vs AA,P=0.032,OR=1.95,95%CI=1.03-3.60;GG vs GA+AA,P=0.002,OR=1.39,95%CI=1.15-1.80).And DNMT3 B rs1569686 T allele was significantly associated with increased risk of gastric cancer(T vs G,P=0.001,OR=1.58,95%CI=1.22-2.04;TT vs TG,P=0.001,OR=1.62,95%CI=1.22-2.17;TT vs TG+GG,P=0.001,OR=1.65,95%CI=1.25-2.19).But,no significant association was observed between rs1569686 and lung cancer,nor between rs2424913 and lung and gastric cancer.However,the haplotype analysis showed that the rs1569686 T/rs2424913 T haplotype was associated with gastric cancer risk.Further,we made a meta-analysis about these three SNPs to access their association with cancer risks.The results indicated that rs1550117 was significantly associated with decreased risk of colorectal cancer,and the association between rs1569686 and gastric cancer remained significant.However,no significance showed between rs2424913 and lung or gastric cancer.Collectively,this is the first research reported the association between DNMT3 A rs1550117 and non-small-cell lung cancer risk,and the association between DNMT3 B rs1569686 and gastric cancer risk,in HuBei province.And our result indicated that rs1550117 and rs1569686 might be used as biomarkers for early screening and prevention of non-small-cell cancer and gastric cancer. |
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