A Molecular Epidemiological Study On The Relationship Between The Genetic Polymorhism Of Xenobiotic-metabolizing Enzymes And Susceptibility To Gastric Cancer

Although gastric cancer (GC) is declining in frequency in the world, its new cases still ranks second ( 755 000 per year), comprising 9.9% of all new malignant cases. GC is responsible for a fourth of all malignant death. In China, GC is the leading cause of cancer death. Jiangsu Province is one of the highest-risk areas of CC in our countiy, with the mortality rate is 33.32 per 100 000. It causes great harm to people's health and life. So it is urgent to find out GC etiology and take effective prevention measures. To reach this target, a population-based molecular epidemiological study on CC was conducted in the two high-risk areas (Jintan and Huai'an County) of Jiangsu Province. Part I The Relationship between Genetic Polymorphism of Cytochrome P450 (CYP2E1) and Susceptibility to Gastric Cancer There are considerable evidences suggesting that human CC is a multistage process with multiple risk factors. Within them, N-nitroso compounds from dietary sources are involved in CC. CYP2E1 is a critical isozyme in metabolizing N-nitrosamines. To explore the association between genetic polymorphism of CYP2E 1 digested by restriction enzyme Rsa I and susceptibility to CC, a 1: 1 matched case-control study was conducted. Genotyping of CYP2E1 was performed using PCR-based RFLP analysis on DNA isolated from peripheral white blood cells from ninety patients with primary CC and ninety control subjects matched according to age, sex, nationality and residential area. 1. Frequencies of CYP2E1 genotype and allele There were three genotypes of CYP2E1 resulting from digestion with restriction enzyme Rsa I type A, a wild-type homozygote cl/cl; type B, the heterozygote cl/c2; and type C, a mutant type homozygote c2/c2. In cases, the frequencies of A (cl/cl) genotype, B (cl/c2) genotype and C(c2/c2) are 71.1%, 24.4% and 4.4% respectively. In controls, the frequencies of A (cl/cl) genotype, B (cl/c2) genotype and C(c2/c2) are 52.2%, 43.3% and 4.4% respectively. There is a significant difference in the frequencies ofA(cl/ci), B(clIc2), C(c2/c2) genotypes( 7.34, df2, P=0.025) between cases and controls. Patients with CC were more likely to be homozygous for the Rsa I genotype cl/cl than controls. The odds ratio of GC for the cl/cl genotype compared with two other genotypes combined was 2.42(95%CN4 . l95.0 1). The frequencies of allele ci and c2 in cases were significantly different from those in controls(X24.77, P=0.028) with the frequencies of allele ci in cases and controls being 83.3% and 16.7% respectively and c2 in cases and controls 73.9% and 26.1% respectively. CYP2E1 is a genetic susceptibility factor involved in the GC carcinogenesis. 2. The combined effect between genetic polymorphism of CYP2E1 and pickle, vegetables on CC Subjects who had A(c 1/cl) genotype of CYP2E1 and ate pickle frequently had 3.89(95%CJ=l.56 s 9.71) folds risk developing CC compared with those who had B(cl/c2) genotype or C(c2/c2) genotype of CYP2E1 and seldom ate pickle. Individuals exposed to A(cl/ci) genotype of CYP2E1 and low intake of vegetables had 5.50(95%CI=2.08拁?4.56) folds risk developing CC compared with those who had B(ci/c2) genotype or C(c2/c2) genotype of CYP2E1 and high intake of vegetables. There lies synergy between genetic polymorphism of CYP2E1 and dietary factors on CC. 3. Comparison of CYP2E 1 gene polymorphism in different races The A(cl/cl) genotype of...