Abstract: Objective To screen and assess genetic risk factors(gene polymorphism) of primary gastric cancer susceptibility and to select the genotype relating to gastric cancer in Han population of Nanjing city.Methods A 1:1 matched case-control study was carried out in 374 primary stomach cancer cases(273 males and 101 females) and gender,age matched controls in Nanjing city.PCR-RFLP and AS-PCR technologies were used to determine the genotypes of CYP2E1,GSTM1,GSTT1,NAT2,ALDH2,MTHFR,XRCC1,IL-1β,VDR,and TNF.Conditional-logistic regression model was adopted to screen the environmental and genetic risk factors of primary gastric cancer and to select the genotype relating to gastric cancer for multi-gene risk analysis.Results The genetic risk factors associated to primary gastric cancer susceptibility were CYP2E1 wild genotype(odds ratioOR=1.348,95% confidence intervalCI=1.075-1.690),NAT2M1 mutant genotype(OR=2.310,95%CI=1.613-3.309),NAT2 slow-acetylating genotype(OR=1.768,95%CI=1.018-3.072),XRCC1 194 mutant genotype(OR=1.449,95%CI=1.140-1.842),MTHFR A1298C mutant genotype(OR=1.521,95%CI=1.11-2.083),IL-1β mutant genotype(OR=1.271,95%CI=1.031-1.568).Multi-gene risk analysis showed that there was a close relation between the OR of polygenic combination and genotypes frequency.Conclusion With the increase of the susceptibility gene,the risk of primary gastric cancer increases.Multi-gene risk assessment can further promote the recognition of susceptible population.