A Case-control Study On The Association Between Genetic Polymorphisms Of CYP1A1, GSTM1 And Gastric Cancer Susceptibility In GuangXi Province

[Background]Gastric cancer is the most common malignant tumor in Chinese population.Epidemiological studies have demonstrated that environmental carcinogens and cigarette smoking,drinking play an important role in gastric carcinogenesis.Most carcinogens are metabolized to their ultimate carcinogens depended on the action of phaseâ… and phaseâ…¡enzymes.Genetic polymorphisms exist in most metabolizing genes encoding metabolizing enzymes.Since metabolizing enzymes play an important role in the metabolic activation and detoxication of precarcinogens and polymorphisms of metabolizing enzymes can change their activities,it is necessary to evaluate the correlation between the polymorphisms of metabolizing enzyme gene and the susceptibility of gastric cancer,which will not only illuminate the molecular mechanism of gastric cancer,but also provide a new route for screening and early diagnosis of gastric cancer.Recently,it has been proved that polymorphisms of CYP 1A1 and GSTM1 genes are closely associated with the risk of gastric cancer.[Objective and method]In order to explore the effects of combined polymorphisms of these genes on gastric cancer susceptibility in Chinese population,polymorphisms of CYP 1A1MSP1 and GSTM1 genes were determined by polymerase chain reaction(PCR)and polymerase chain reaction-restriction fragment length polymo- rphisms(PCR-RFLP)in 121 patients with gastric cancer and 138 normal controls in Chinese GuangXi subjects.The associations between genetic polymorphisms and susceptibility of gastric cancer in Chinese GuangXi subjects were analyzed.The interaction among genotypes,smoking status,drinking status and gastric cancer susceptibility were also analyzed.The feasibility of gastric mucosa samples and peripheral blood samples used in evaluating genetic polymorphisms was discussed,too.[Results]The results in this study showed as follows:1.The frequency of CYP 1A1 MSP1 genotypes(m1/m1,m1/m2,m2/m2) in gastric cancer group and control group was 35.5%,43.0%,21.5%and 41.3%,39.1%,19.6%,respectively.No significant differences in CYP 1A1 MSP1 genotype distributions were found between the two groups (X^2a=0.901,P^a=0.342).2.Compared with CYP 1A1 m1/m1 genotype carriers,the estimated relative risk for CYP 1A1 m1/m2 and CYP 1A1 m2/m2 genotype carriers was 1.276 and 1.276,respectively.After adjustment with age,gender,nationality, smoking status and drinking status,the risk in the individuals who carried with at least one CYP 1A1 m2 allele genotype was higher than those carrying CYP 1A1 m1/m1 genotype,but no remarkable relationship was observed between the difference(OR^a=1.509,95%CI=0.846-2.690,P^a=0.342).3.Considering smoking status,the individuals who carried with at least one CYP 1A1 m2 allele genotype had increased gastric cancer risk than those who carried with CYP 1A1 m1/m1 genotype in both non-smokers and smokers,but no significant difference was observed between the two groups(P＞0.05).After adjusted for age,gender,nationality and drinking status,the risk in the individuals carrying CYP 1A1 m1/m2 or CYP 1A1 m2/m2 genotype was higher than those who carried with CYP 1A1 m1/m1 genotype,but still no noticeable relationship can be observed(adjusted OR=1.826,1.148;95%CI= 0.649-5.138,0.493-2.675;P=0.193,0.749,respectively).4.Considering drinking status,the individuals who carried with at least one CYP 1A1 m2 allele genotype had increased gastric cancer risk than those who carried with m1/m1 genotype in both non- drinkers and drinkers,but no significant difference was observed between the two groups(P＞0.05).After adjusted for age,gender,nationality and smoking status,the risk in the individuals carrying CYP 1A1 m1/m2 or CYP 1A1 m2/m2 genotype was higher than those who carried with CYP 1A1 m1/m1 genotype,but still no remarkable association can be observed(adjustedOR=1.352,1.375;95%CI=0.735-2.488, 0.384-4.216;P=0.444,0.885,respectively).5.The frequency of GSTM1 null genotype in gastric cancer group was significantly higher than that in control group(54.5%vs 39.1%,X²=6.161, P=0.017).It remained significant(adjusted X²=6.140,P=0.013)after adjustment for age,gender,nationality,smoking status and drinking status).6.The individuals who carried with GSTM1 null genotype had a 2.13 fold increased risk of gastric cancer(95%CI=1.079-1.831,P=0.013)than those carried with GSTM1(+)genotype after data was stratified by age,gender, nationality,smoking status and drinking status.7.GSTM1 null genotype remarkably increased gastric cancer risk in smokers.The individuals who carried with GSTM1 null genotype had increased gastric cancer risk than those carrying GSTM1(+)genotype in smoking group (OR^a=3.247,95%CI=1.067-2.328,P^a=0.015),which were also highter than overall risk for gastric cancer(OR^a=2.129).8.GSTM1 null genotype increased gastric cancer risk in drinkers.The individuals who carried with GSTM1 null genotype had increased gastric cancer risk than those carrying GSTM1(+)genotype in drinking group(OR^a=3.117, 95%CI=1.020-2.863,P^a=0.033),which were also highter than overall risk for gastric cancer(OR^a=2.129).9.Compared with people who had the combination of GSTM1(+)genotype and CYP 1A1 m1/m1 genotype,the odds ratio of gastric cancer for the combination of GSTM1 null and CYP 1A1 m1/m1 genotype was 1.749 (P^a=0.382).The odds ratio of gastric cancer for the combination of GSTM1 null and at least one CYP 1A1 m2 genotype was 2.327(P^a=0.030).Combination of GSTM1 null genotype and at least one CYP 1A1 m2 genotype significantly increased gastric cancer susceptibility.10.CYP 1A1 and GSTM1 genotype among gastric mucosa and peripheral blood samples was the same in the same individuals with gastric cancer.[Conclusion]1.There is no obvious relationship between the CYP 1A1 MSP1 polymorphisms and gastric cancer in Chinese GuangXi subjects.2.GSTM1 null genotype is closely associated with increased risk for gastric cancer in Chinese GuangXi population.3.GSTM1 null genotype remarkably increases gastric cancer susceptibility in smokers.4.GSTM1 null genotype remarkably increases gastric cancer susceptibility in drinkers.5.The combination of GSTM1 null genotype and CYP 1A1 m2 genotype can increase gastric cancer susceptibility in Chinese GuangXi subjects.6.peripheral blood sample and gastric mucosa sample is equivalent in the evaluation of CYP 1A1 and GSTM1 genes polymorphisms.