AIM:To clarify the association between CYP2E1 PstⅠ/RsaⅠ polymorphism and susceptibility to colorectal cancer.METHODS:A meta-analysis based on 10 eligible casecontrol studies involving 4979 cases and 6012 controls wa...AIM:To clarify the association between CYP2E1 PstⅠ/RsaⅠ polymorphism and susceptibility to colorectal cancer.METHODS:A meta-analysis based on 10 eligible casecontrol studies involving 4979 cases and 6012 controls was carried out to summarize the data on the association between CYP2E1 RsaⅠ/PstⅠ polymorphism and colorectal cancer risk.RESULTS:In comparison of the homozygote c2c2 and c2 carriers(c1c2 + c2c2) and the homozygous wild-type genotype(c1c1),no association was found between CYP2E1 RsaⅠ/PstⅠ polymorphism and colorectal cancer risk [odds ratio(OR)=1.24(95% CI:0.93-1.66) for c2c2;OR = 1.02(95% CI:0.88-1.19) for c2 carriers].In stratif ied analysis,Caucasians with c2c2 homozygote appeared to have an increased risk of colorectal cancer(OR=2.67,95% CI:1.03-6.89,P=0.043),no signif icant associations were found in other groups.CONCLUSION:c2c2 homozygote of CYP2E1 PstⅠ/RsaⅠ polymorphism may be associated with the increased risk of colorectal cancer in Caucasians,which needs further investigations.展开更多
AIM: Genetic polymorphism in enzymes of carcinogen metabolism has been found to have the influence on the susceptibility to cancer. Cytochrome P450 2E1 ( CYP2 E1) is considered to play an important role in the metabol...AIM: Genetic polymorphism in enzymes of carcinogen metabolism has been found to have the influence on the susceptibility to cancer. Cytochrome P450 2E1 ( CYP2 E1) is considered to play an important role in the metabolic activation of procarcinogens such as N-nitroscoamines and Iow molecular weight organic compounds. The purpose of this study is to determine whether CYP450 2Elpolymorphisms are associated with risk s of gastric cancer.METHODS: We conducted a population based case-control study in Changle county, Fujian Province, a high-risk region of gastric cancer in China. Ninety-one incident gastric cancer patients and ninety-four healthy controls were included in our study. Datas including dsmographic characteristcs, diet intake, and alcohol and tobacco consumption of indivduals in our study were completed by a standardized questionnaire. PCR-RFLP revealed three genotypes: heterozygote (C1/C2) and two homozygotes (C1/C1 and C2/C2) in CYP2E1.RESULTS: The frequency of variant genotypes (C1/C2 and C2/C2) in gastric cancer cases and controls was 36.3% and 24.5%, respectively. The rare homozygous C2/C2 genotype was found in 6 indivduals in gastric cancer group(6.6%),whereas there was only one in the control group (1.1%).However, there was no statistically significan difference between the two groups (two-tailed Fisher′s exact test, P =0.066). Indivduals in gastric cancer group were more likely to carry genotype C1/C2 (odds ratio, OR = 1.50) and C2/C2(OR = 7.34) than indivduals in control group (X2 = 4.597, for trend P=0.032). The frequencies of genofypes with the C2allele ( C1/C2 and C2/C2 genotypes) were compared with those of genotypes without C2 allele ( C1/C1 genotype )among indivduals in gastric cancer group and control group according to the pattern of gastric cancer risk factors. The results show that indivduals who exposed to these gastric cancer risk factors and carry the C2 allele seemed to have a higher risk of developing gastric cancer.CONCLUSION: Polymorphism of CYP2E1 gene may have some effct in the development of gastric cancer in Changle county, Fujian Province.展开更多
Polymorphic cytochrome P4502E1 (CYP2E1) plays an important role in the metabolic activation of many carcinogens. We have previously shown that the c1/c1 genotype recognized by Rsa I in the 5′-regulatory region of the...Polymorphic cytochrome P4502E1 (CYP2E1) plays an important role in the metabolic activation of many carcinogens. We have previously shown that the c1/c1 genotype recognized by Rsa I in the 5′-regulatory region of the CYP2E1 may be a susceptibility factor for developing esophageal cancer and lung cancer in Chinese. The present study was to investigate the relationship between the Rsa I genotype and the expression of CYP2E1 in human livers. A total of 50 liver specimens were genotyped for CYP2E1 and assayed for CYP2E1 protein contents and functional activity by using specific antibody in immunoblot and a probe substrate, p-nitrophenol. A considerable interindividual variation in CYP2E1 protein (20-fold) and functional activity (56-fold) was observed among these liver samples. However, when they were categorized according to genotype, the mean content of CYP2E1 protein was significantly higher among individuals with the c1/c1 genotype than that among those having c1/c2 or c2/c2 genotype [124.0±83.9 pmol/mg (n = 28) versus 65.5±38.9 pmol/mg (n = 22), P＜0.01 . The mean activity of CYP2E1 towards p-nitrophenol for the c1/c1 genotype was also higher than that for the variant genotypes (198.4±27.8 pmol/min/mg versus 101.2±18.1 pmol-1·min-1·mg-1, P＜0.01 . Also, the protein levels and functional activity showed a significant correlation (r = 0.68, P＜0.01 . These results demonstrate an association between the Rsa I genotype and the phenotype of CYP2E1 in our samples, and the data are compatible with the assumption that CYP2E1 c1/c1 genotype is a susceptibility factor for certain cancers in Chinese.展开更多
文摘AIM:To clarify the association between CYP2E1 PstⅠ/RsaⅠ polymorphism and susceptibility to colorectal cancer.METHODS:A meta-analysis based on 10 eligible casecontrol studies involving 4979 cases and 6012 controls was carried out to summarize the data on the association between CYP2E1 RsaⅠ/PstⅠ polymorphism and colorectal cancer risk.RESULTS:In comparison of the homozygote c2c2 and c2 carriers(c1c2 + c2c2) and the homozygous wild-type genotype(c1c1),no association was found between CYP2E1 RsaⅠ/PstⅠ polymorphism and colorectal cancer risk [odds ratio(OR)=1.24(95% CI:0.93-1.66) for c2c2;OR = 1.02(95% CI:0.88-1.19) for c2 carriers].In stratif ied analysis,Caucasians with c2c2 homozygote appeared to have an increased risk of colorectal cancer(OR=2.67,95% CI:1.03-6.89,P=0.043),no signif icant associations were found in other groups.CONCLUSION:c2c2 homozygote of CYP2E1 PstⅠ/RsaⅠ polymorphism may be associated with the increased risk of colorectal cancer in Caucasians,which needs further investigations.
基金Supported by Natural Science Foundation of Fujian Province,China,No.C001009
文摘AIM: Genetic polymorphism in enzymes of carcinogen metabolism has been found to have the influence on the susceptibility to cancer. Cytochrome P450 2E1 ( CYP2 E1) is considered to play an important role in the metabolic activation of procarcinogens such as N-nitroscoamines and Iow molecular weight organic compounds. The purpose of this study is to determine whether CYP450 2Elpolymorphisms are associated with risk s of gastric cancer.METHODS: We conducted a population based case-control study in Changle county, Fujian Province, a high-risk region of gastric cancer in China. Ninety-one incident gastric cancer patients and ninety-four healthy controls were included in our study. Datas including dsmographic characteristcs, diet intake, and alcohol and tobacco consumption of indivduals in our study were completed by a standardized questionnaire. PCR-RFLP revealed three genotypes: heterozygote (C1/C2) and two homozygotes (C1/C1 and C2/C2) in CYP2E1.RESULTS: The frequency of variant genotypes (C1/C2 and C2/C2) in gastric cancer cases and controls was 36.3% and 24.5%, respectively. The rare homozygous C2/C2 genotype was found in 6 indivduals in gastric cancer group(6.6%),whereas there was only one in the control group (1.1%).However, there was no statistically significan difference between the two groups (two-tailed Fisher′s exact test, P =0.066). Indivduals in gastric cancer group were more likely to carry genotype C1/C2 (odds ratio, OR = 1.50) and C2/C2(OR = 7.34) than indivduals in control group (X2 = 4.597, for trend P=0.032). The frequencies of genofypes with the C2allele ( C1/C2 and C2/C2 genotypes) were compared with those of genotypes without C2 allele ( C1/C1 genotype )among indivduals in gastric cancer group and control group according to the pattern of gastric cancer risk factors. The results show that indivduals who exposed to these gastric cancer risk factors and carry the C2 allele seemed to have a higher risk of developing gastric cancer.CONCLUSION: Polymorphism of CYP2E1 gene may have some effct in the development of gastric cancer in Changle county, Fujian Province.
基金This work was supported in part by the National Natural Science Foundation of China (Grant Nos. 39825122 and 39990570) and State Key Basic Research Program (Grant No. G1998051200).
文摘Polymorphic cytochrome P4502E1 (CYP2E1) plays an important role in the metabolic activation of many carcinogens. We have previously shown that the c1/c1 genotype recognized by Rsa I in the 5′-regulatory region of the CYP2E1 may be a susceptibility factor for developing esophageal cancer and lung cancer in Chinese. The present study was to investigate the relationship between the Rsa I genotype and the expression of CYP2E1 in human livers. A total of 50 liver specimens were genotyped for CYP2E1 and assayed for CYP2E1 protein contents and functional activity by using specific antibody in immunoblot and a probe substrate, p-nitrophenol. A considerable interindividual variation in CYP2E1 protein (20-fold) and functional activity (56-fold) was observed among these liver samples. However, when they were categorized according to genotype, the mean content of CYP2E1 protein was significantly higher among individuals with the c1/c1 genotype than that among those having c1/c2 or c2/c2 genotype [124.0±83.9 pmol/mg (n = 28) versus 65.5±38.9 pmol/mg (n = 22), P＜0.01 . The mean activity of CYP2E1 towards p-nitrophenol for the c1/c1 genotype was also higher than that for the variant genotypes (198.4±27.8 pmol/min/mg versus 101.2±18.1 pmol-1·min-1·mg-1, P＜0.01 . Also, the protein levels and functional activity showed a significant correlation (r = 0.68, P＜0.01 . These results demonstrate an association between the Rsa I genotype and the phenotype of CYP2E1 in our samples, and the data are compatible with the assumption that CYP2E1 c1/c1 genotype is a susceptibility factor for certain cancers in Chinese.
