The Relationship Between CYP1A1, GSTM1 And GSTT1 Genetic Polymorphisms And Susceptibility Of Esophageal Carcinoma In Wuwei District Of Gansu Province

Esophageal carcinoma (EC) is one of the most common malignant diseases in the world,and EC's incidence and mortality rates are also in a high level in China. Both environmental and genetic factors may play an important role in the tumorgenesis and development of EC. Many chemical compounds present in environment undergo metabolic activation by phase enzymes, some result in creation of ultimate carcinogens. The phase enzymes act on these carcinogens, transforming them into inactivated compounds that are excreted. There are considerable evidences suggesting that human esophageal carcinoma is a multistage process with multiple risk factors.[Objective] To study the association between genetic polymorphism of CYP1A1 and/or GSTM1,GSTT1 and susceptibility to esophageal carcinoma in Wuwei District of Gansu province.[Methods] In order to explore the effects of combined polymorphisms of CYP1A1,GSTM1 and GSTT1 genes on esophageal carcinoma susceptibility in Chinese population, polymorphisms of these genes were detected in 189 patients with esophageal carcinoma and 216 healthy controls in Wuwei District by PCR-based RFLP analysis.[Results] 1. The relationship between frequencies of CYP1A1 genotype and susceptibility to esophageal carcinoma. There were three genotypes of CYP1A1 resulting from digestion with restriction enzyme MspI : type A , a wild-type homozygote T/T; type B ,the heterozygote T/C ; and type C, a mutant type homozygote C/C. In cases, the frequencies of A , B and C genotypes are 25.9%, 50.3% and 23.8%,respectively.In controls,the frequencies of A, B and C genotypes are 32.4%, 45.4% and 22.2% ,respectively. There is no significant difference in the frequencies of A ,B and C genotypes(x~2=2.041, P=0.153).2. The frequency of GSTM1-null genotype in esophageal carcinoma group was significantly higher than that in control group (x~2=9.462, P=0.002). The individuals who carried with GSTM1-null genotype had a 1.956 fold increase risk of esophageal carcinoma.3. There was no difference of the frequency of GSTT1-null genotype in esophageal carcinoma and control group(x~2=2.808. .P=0.094). The individuals who carried with GSTM1-null genotype didnot increase the risk of esophageal carcinoma.4. When combination of polymorphism of GSTM1,GSTT1 genotype was analyzed, the risk of esophageal carcinoma combination of GSTM1-null and GSTT1-null was increased (OR=1.795, 95%CI=1.085～2.924).5. The combination of CYP1A1(T/C or C/C) and GSTM1-null,GSTT1-null genotypes is associated with the risk of esophageal carcinoma.[Conclusions] Both the variation of CYP1A1 gene and GSTT1 null genotype alone might not be associated with the susceptibility of esophageal carcinoma but GSTM1 null genotype alone or combined with GSTT1 null genotype or the 3801 T-C variation of CYP1A1 gene were correlated with esophageal carcinoma. These results suggest that GSTM1 null genotype alone or in combination with other defective genotypes might serve as risk factors to the esophageal carcinoma.