Genetic Polymorphisms Of Metabolic Enzymes And Gastric Carcinoma Susceptibility

Objective:On the basis of investigating the distribution frequencies of genetic polymorphisms of phaseⅠmetabolic enzymes such as cytochrome P450 1A1(CYP1A1),CYP2D6 and phaseⅡmetabolic enzymes including glutathione S-transferase M1(GSTM1) and T1(GSTT1) genotypes in gastric carcinoma patients and healthy controls among the population of Hunan in China,this study is to explore the relationship between these gene polymorphisms and gastric carcinoma susceptibility.Methods:CYP1A1~*2A polymorphism,CYP2D6~*Ch polymorphism,GSTM1 and GSTT1 gene deletion polymorphisms between 129 healthy controls and 123 cases of gastric carcinoma patients were investigated by using PCR and PCR-RFLP techniques.The frequencies of the genotypes were analyzed through case-control methods.Results:There was no significant differences among the frequencies of CYP1A1 and/or CYP2D6 gene's wild type(W/W),heterozygous mutation type(W/M) and homozygous mutation type(M/M) between the gastric carcinoma group and control group(P＞0.05).The difference in the frequencies of GSTM1 null-type(GSTM1-/-) was significant(P=0.001), and there were significant differences in the frequencies of GSTM1 null-type(GSTM1-/-) in 4 kinds of clinical adenocarcinoma pathology types:well-differentiated tumor(77.1%,P=0.030),middle-differentiated tumor(81.8%,P=0.034),middle-undifferentiated tumor(70.6%,P=0.019) and undifferentiated tumor(73.5%,P=0.039),separately.The difference in GSTT1 null-type(GSTT1-/-) was significant(P=0.039),but there were not significant differences(P＞0.05) in the frequencies of GSTT1 null-type in the montioned 4 kinds of clinical adenocarcinoma pathology types: well-differentiated tumor(60.0%),middle-differentiated tumor(68.2%), middle-undifferentiated tumor(64.7%) and undifferentiated tumor(61.2 %),respectively.Excluding the influence from other factors,GSTM1 null-type showed an increased risk of gastric carcinoma in middle-undifferentiated tumor(OR=2.532,95%C.I.1.738-6.692) and undifferentiated tumor(OR=1.960,95%C.I.1.911-4.220).GSTT1 null-type showed an increased risk of gastric carcinoma in middle-undifferentiated tumor(OR=1.630,95%C.I.1.201-2.371).An extremly increased risk of gastric carcinoma in the individuals with combined deficiency of GSTM1 and GSTT1 genes was seen(p=0.001). Unhealthy indulgence such as smoking increased the risk of gastric carcinoma in the individuals with GSTM1-null genotype(OR=4.694,95% C.I.1.758-12.533).Conclusions:The genotypes of CYP1A1~*2A and/or CYP2D6~*Ch are not correlating with gastric carcinoma susceptibility.GSTM1(-/-) genotype increases the risk of gastric carcinoma.GSTT1(-/-) genotype increases the risk of middle-undifferentiated gastric tumor.The combined deficiency genotype of GSTM1 and GSTT1 increases the risk of gastric carcinoma.And the unhealthy indulgence such as smoking increases the risk of gastric carcinoma in GSTM1(-/-) individuals.It is suggested that GSTM1-null genotype may be susceptibly factor to gastric carcinoma, and play a role together with the other influence factors.