Study On Genetic Polymorphisms Of Metabolic Enzymes And Environmental Exposure Associated With Gastric Cancer

OBJECTIVE: In order to screen the environmental and genetic risks factors and estimate the population attributable risk for risks factors and achieve a better insight into the interaction of environment and gene in the susceptibility to gastric cancer. METHODS: A 1∶1 case-control study was carried out in Nanjing area , using PCR-RFLP technology to determined the genetic polymorphisms of GSTM1,GSTT1,CYP2E1,NAT2 in case and control. Epidemiology datum about environmental exposure was gathered in person interview. Single or multiple Conditional-Logistic regression model were presumed to screen the environmental and genetic risks factors of gastric cancer. Adjusted attributable risk (ARc%)and Summary population attributable risk (sAR) were calculated to estimate the effect for each risk factor and co-effect of all risk factors in gastric cancer among 121 cases of gastric cancer patients and controls. Gene-environment interaction was analysed to explore their co-effect in gastric cancer. Further analysis were applied to screen the environmental and genetic risks factors based on different sex.RESULTS: The environmental risk factors of family history of digestive system disease,tobacco smoking,pickled food,irregular diet habit were statistically significant, which OR were respectively 8.439(95%CI=1.399～50.899),2.104(95%CI=1.044～4.241),1.550(95%CI=1.059～2.269),1.720(1.143～2.588). The result shows that sAR of the risks as such amount to 54.7% in Nanjing area, namely the incidence of gastric cancer would decrease 54.7%, when the risk factors were diminished simultaneously. People who carried CYP2E1 c1/c1 genotype have higher risk of gastric cancer(OR=1.883,95%CI=1.179～3.003); NAT2 M1 mutation genotype was significantly associated with the increase of the risk of gastric cancer(OR=11.079,95%CI=4.421～27.765). Combined with environmental and genetic risk factors sAR increased to 69.7%. An interaction was observed in gene-environment co-effect in gastric cancer. In male, the risk factors were separately family history of tumor,tobacco smoking,raw food,irregular diet,genetic polymorphisms of CYP2E1 and NAT2 M1, etc. sAR account for 81.4%; interaction of gene-environment was also observed in this study. Irregular diet and NAT2 M1 mutation were the main risk factors in female for the limitation of sample-capacity.CONCLUSION: CYP2E1 RsaⅠc1/c1 was assiociated with the increase of gastric cancer whereas NAT2 M1 mutation was the risk factor; environmental factors play important roles and interaction of gene-environment were found in in the development of gastric cancer.