Genetic Polymorphism Of GSTT₁ And EPHX And The Risk Of Hepatocellular Carcinoma From Guangxi District

Genetic Polymorphism of GSTT1 and EPHX and the Risk of Hepatocellular Carcinoma from Guangxi District.OBJECTIVE: To study the relationship between the two detoxification enzyme genes (GSTT1 and EPHX) and the risk of hepatocellular carcinoma .METHODS :The peripheral blood samples of all the subjects including 53 healthy people , 51 HCC and 46 NPC patients were collected from the same local region in Guangxi where AFB1 was highly contaminated and HBV was prevalent, DNAs were extracted from their WBC(white blood cell--- WBC).The GSTT1 gene and 139 codon of EPHX polymorphism were detected by PCR and PCR-RFLP techniques with two pairs of specific primer.RESULTS: 1. In the HCC high risk region,the frequences of GSTT1 null genotype in the normal subjects , HCC patients and NPC patients were 33.96%(18/53), 54.9%(28/51) and 60.87%(28/46),respectively. The HCC patients were significantly higher than the normal subjects (p<0.05) with an OR of 2.367 .The NPC patients had a similar relationship with the normal subjects as HCC patients had done ,which the OR was 3.205. There was not significant difference between the HCC patients and the NPC patients . 2.The mutation rate of EPHX 139 codon which encode arginine (Arg ,the high activity phenotype) in the normal subjects and HCC patients were 13.1%(7/53) and 10.0% (5/50) .The normal subjcts had a slight higher tendency of EPHX 139 Arg frequency than the HCC patients,but there was no significant difference. 3.Two-gene-combination analysis suggested that EPHX of low activity genotype encoding histidine in combination with GSTT1 null genotype significantly increased HCC risk .CONCLUSION: 1. The results suggest that GSTT1 gene deletion may play an important role for susceptibility to HCC . 2..The EPHX histidine residence at 139 site of exon 4 is the most common genotype, which may be responsible for HCC susceptibility. But EPHX 139 homozygous His has not significant increased risk in HCC susceptibility. 3. A combination of several abnormalities of detoxific enzyme display the specific interaction with HCC. These show indirectly that the chemical toxicant may play an important role in GuangxiHCC etiology and that multiple gene-environment factors combination cause HCC.