Case-Control Study On The Association Of Hepatocellular Carcinoma With Genetic Polymorphisms Of CYP3A5,CYP3A7 In High Contaminated Area Of Aflatoxin B1

Backgrounds and Aims:The morbility of hepatocellular carcinoma(HCC) is highly associated with aflatoxin B1(AFB1)contaminating in food.AFB1 requires to oxidize to AFB1-exo-8,9-epoxide(AFBO)by cytochrome P450 (CYP450)to exert its carcinogenic effects.The CYP3A isozyme is the most abundant and important in the CYP450 family.CYP3A5 and CYP3A7 are two members of CYP3A,their gene polymorphisms can affect the level of protein expression and oxidation activity.A single nucleotide polymorphisms(SNP) within CYP3A5 intron 3(g.6986 A＞G)is the primary cause of the CYP3A5 mRNA and protein polymorphism.People carrying g.6986A(CYP3AS~*1) homozygote and heterozygote has a higher protein expression level. CYP3A7~*1C allele is a cause of polymorphism of CYP3A7 protein expression,which arises from the replacement of a 60bp -length in the CYP3A7 promoter by the corresponding region of CYP3A4.To investigate the relationships between the two gene polymorphisms and susceptibility to HCC,The present study analysied the two genetypes in HCC patients and controls in high prevalent areas of HCC in Guangxi.Methods:Case-control study.Peripheral blood samples from 97 HCC patients,38 HBV positive cases and 75 HBV negative cases were Collect from the First Affiliated Hospital of Guangxi Medical University and Cancer hospital during 2005.12 to 2006.9.Genomic DNA was isolated from peripheral blood white blood cells,PCR-RFLP assay was used for the analysis.Results:(1).CYP3A5~*1 allele frequency is no difference among HCC,HBV positive and HBV negative healthy adults of Guangxi population.(2) CYP3A5~*1 allele frequency and the proportion of(CYP3A5~*1/~*1+ CYP3A5~*1/~*3)genetypes are both higher in Guangxi population,as compared with the reports from Guangdong,Hunan and Singapore healthy Chinese adults.There are siginificant differences.(3).CYP3A7~*1C allele is not detected in this cohort of Guangxi population.Conclusion:(1).This study shows CYP3A5~*1 allele frequency is no difference among HCC patients and controls in this area.However,CYP3A5~*1 allele frequency in this area is higher than other areas.We speculate that CYP3A5 may take part in the morbility of AFB1 related HCC.but it should be verified in a larger samples.(2).CYP3A7~*1C allele is not detected in this cohort,which hints CYP3A7 maybe influence little on the morbility of AFB1 related HCC.