Correlation Between DNA Pepair Gene XRCC1 Single Nucleotide Polymorphism And Susceptibility To Hepatocellular Carcinoma In Fusui County Of Guangxi

Objective : To study the relationship of DNA repair gene XRCC1 polymorphism and genetic susceptibility to hepatocellular carcinoma between the population of Zhuang and Han Nationality in FuSui County of GuangXi.Methods:Case-Control study of 50 patients with HCC and 30 health controls from Zhuang and Han Nationality respectively,74 HCC family history group and 24 high-risk group from Zhuang Nationality in local high-risk region,were conducted to detect XRCC1 polymorphism at Arg194Trp,Arg280His and Arg399Gln.Their genotypes frequencies and allelic frequencies were analyzed by PCR-RFLP and sequencing.All of them were examined in epidemiology,including history of smoking,drinking and age.Results:1.XRCC1-194Trp allele is associated with decreasing HCC risk in Zhuang and Han Nationality;XRCC1399Gln/Gln is associated with increasing HCC risk in Zhuang Nationality,while the decreasing HCC risk in Han Nationality.2.Among HBV carriers,with XRCC1 -194Trp allele had a high risk for HCC between the HCC case group and the individuals with HCC family history,while there were no statistically significant(P>0.05);Among non-HBV carriers,with XRCC1 -194Trp allele had a low risk for HCC(aOR=0.103,95%CI=0.012-0.905,P=0.040),while with XRCC1 399Gln/Gln had a high risk for HCC(aOR=7.211,95%CI=1.513-34.363,P=0.013).With XRCC1 -280His allele had a high risk for HCC in late-onse(t>50 years)HCC,while had a low risk for HCC in early-onset(≤50 years).3.The alleles of XRCC1-194Trp,-280His and-399Gln paralleled with HBV infection had high risk for HCC development ( aOR=106.393 ,95%CI=8.838-1280.823,P=0.000,a OR=16.200,95%CI=1.565-167.738,P=0.020和aOR=8.505,95%CI=2.129-33.969,P=0.002,respectively).Com- pared to late-onset(>50 years)HCC,with XRCC1 -194Trp,-280His and -399Gln alleles had a low risk for HCC in early-onset(≤50 years).4.Compared the HCC patients from FuSui,with XRCC1 -399Gln/Gln had a high risk for HCC(aOR=3.018,95%CI=0.915-9.345,P=0.055),while there were no statistically significant(P>0.05).5.Compared the HBV carriers from FuSui,with XRCC1 -194Arg/Trp had a high risk for HCC , this was statistically significant ( aOR=5.581 ,95%CI=1.024-30.423,P=0.047).6.The combined analyses of theXRCC1 genotype in Han Nationality,individuals with With 194Trp-280Arg/Arg-399Arg/Arg and 194Arg/Arg -280Arg/Arg-399Arg/Gln genotype have a low risk of HCC(OR=0.083,95%CI=0.009-0.782,P=0.020;OR=0.067,95%CI=0.007-0.627,P=0.008,respectively ). While in Zhuang Nationality , individuals with 194Trp-280Arg/Arg-399Arg/Arg,194Arg/Arg-280Hs-399Arg/Arg and 194Arg/Arg -280Arg/Arg-399Arg/Gln genotype have a high risk of HCC,there were no statistically significant(P>0.05). 7.No statistically significant differences were observed in the alleles or in the genotype frequencies of the XRCC1 Arg194Trp,Arg280His和Arg399Gln gene polymorphisms between the population of Zhuang and Han Nationality,as well as the Zhuang and Han HCC case groups(P>0.05).Conclusion:1.Among non-HBV carriers from Zhuang Nationality,the XRCC1 -194Trp allele is associated with decreasing HCC risk,while the XRCC1 399Gln/Gln is associated with increasing HCC risk.2.Among HBV carriers from FuSui,the XRCC1 -194Trp allele is associated with increasing HCC risk.3.XRCC1-194Trp,-280His and -399Gln alleles paralleled with HBV infection had high risk for HCC development in Zhuang Nationality.4.XRCC1 -399Gln polymorphism had associated with late-onset(>50 years)HCC in Zhuang Nationality. Objective : To explore the relationship between susceptibility of hepatocellular carcinoma and single nucleotide polymorphism distribution of caspase 9(CAS9)as the key role in the apoptosis pathway.Methods:Case-Control study of 50 patients with HCC and 30 health controls from Zhuang and Han Nationality respectively,74 HCC family history group and 24 high-risk group from Zhuang Nationality in local high-risk region,were conducted to detect Caspase 9 polymorphism at rs2308938,rs9282624 and rs1052576.Their genotypes frequencies and allelic frequencies were analyzed by PCR-RFLP and sequencing.All of them were examined in epidemiology,including sex,age and history of smoking,drinking.Results:1.The frequencies of rs2308938 Val alleles and mutant Leu alleles were 0.0% and 100.0% in each group.2.The frequencies of rs9282624 Ile alleles and mutant Leu alleles were 100.0% and 0.0% in each group.3.Correlation between rs1052576(Arg221Gln) polymorphism and susceptibility to Hepatocellular Carcinoma.3.1 Among HBV carriers,a trend of increasing HCC risk with increasing number of -221Gln allele between the HCC case group and the individuals with HCC family history;Among non-HBV carriers,with -221Gln allele had a low risk for HCC between the 2 groups,while there were no statistically significant(P>0.05).The -221SNP and HBV infection were associated with HCC development(aOR=6.642,95%CI=1.384-31.882,P=0.018).3.2 In the stratified analyses,the -221Gln allele containing genotypes were proned to increase the risk for HCC among the HBV carriers.3.3 The alleles of -221Gln paralleled with HBV infection had high risk for HCC development(aOR=41.535,95%CI=7.518-229.481,P=0.000).Male individuals with Arg/Gln or Gln/Gln genotype had a high risk for HCC(aOR=3.989,95%CI=0.627-25.389,P>0.05).3.4 Compared the HCC patients from FuSui,a trend of increasing HCC risk with increasing number of -221Gln allele while this was no statistically significant(P>0.05).3.5 No statistically significant differences were observed in the alleles or in the genotype frequencies of the Caspase 9-Arg221Gln gene polymorphisms between the population of Zhuang and Han Nationality(P>0.05).3.6 Compared HCC case group between the Zhuang and Han Nationality,the frequencies of -221Arg/Arg,Arg/Gln和Gln/Gln were 48.0%,36.0% and 16.0% in the HCC patients from Zhuang Nationality,respectively,and 32.0%,58.0% and 10.0% in the HCC patients from Han Nationality;there was no significant difference among them(p>0.05).4 . There was no obvious correlation for XRCC1 and Caspase 9 polymorphism and HCC through the combined analyses of the XRCC1 and Caspase 9 genotype.Conclusion:1.Caspase 9 -221SNP(rs1052576) and HBV infection were associated with HCC developmen(taOR=6.642,95%CI=1.384-31.882,P=0.018).-221Gln allele paralleled with HBV infection had high risk for HCC development in Zhuang Nationality.2 . There is no obvious correlation for rs2308937 and rs9282624 polymorphism and HCC between Zhuang and Han Nationality in Fusui.