The Associations Between Genetic Polymorphisms Of HOGG1, TP53 And P21^WAF-1/CIP-1 And The Alterations Of Aminotransferases Levels After Transcatheter Arterial Chemotherapy In Hepatocellular Carcinoma Patients

ObjectiveWe investigated the associations between the genetic polymorghisms of hOGG1, TP53 and p21^WAF-1/CIP-1 and the alterations of liver function indices(ALT, AST) after transcatheter arterial chemotherapy (TAC) in hepatocellular carcinoma (HCC) patients, to explore the effect of genetic background of hOGG1, TP53 and p21^WAF-1/CIP-1 on the capability of oxidative DNA damage and repair under the challenge of chemotherapeutics.Materials and MethodsPolymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were employed to detect the genetic polymorphisms of hOGG1, TP53 and p21^WAF-1/CIP-1 in 31 HCC patients from Guangxi, China. And the association between the genetic polymorphisms of hOGG1, TP53 and p21^WAF-1/CIP-1(hOGG1 Cys326Ser,TP53 Arg72Pro,p21^WAF-1/CIP-1 Ser31Arg)and the alterations of Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) level in these patients after TAC was analyzed.Results1,hOGG1 Cys326Ser: AST levels in non-Cys/Cys (Ser/Ser and Ser/Cys) carriers are significant different among the three time points (F=4.453, P=0.049). AST levels at day-1 and day-3 after TAC was higher than the day before TAC (P=0.010, P=0.040). AST levels at day-3 after TAC was higher than day-1 after TAC (P=0.038).2,TP53 Arg72Pro: AST levels in Arg/Pro carriers are significant different among the three time points (F=10.451, P=0.022). AST levels at day-1 and day-3 after TAC was higher than the day before TAC (P=0.016, P=0.022). AST levels at day-3 after TAC was higher than day-1 after TAC (P=0.028).3,p21^WAF-1/CIP-1 Ser31Arg: AST levels in Ser/Ser carriers are significant different among the three time points (F=12.212, P=0.002). AST levels at day-1 and day-3 after TAC was higher than the day before TAC (P=0.005, P=0.003). AST levels at day-3 after TAC was higher than day-1 after TAC (P=0.008).4,The result of multiple linear regression analysis showed:â‘ At day-1 after TAC, the higher Epirubicin dose administered, the higher ALT and AST levels were (δALT¹:β=0.762, P=0.010;δAST¹:β=0.922, P=0.001) .â‘¡At day-3 after TAC, the higher Fluorouracil dose administered, the higher ALT and AST levels were (δALT³?β=0.473 , P=0.008 ;δAST³ : (3=0.601 , P=0.000) .â‘¢Compared with Han patients, the ALT and AST levels in Zhuang patients are lower at day-1 after TAC (δALT¹:β=-0.573, P=0.037;δAST¹:β=-0.484, P=0.064) .â‘£The ALT level was lower among patients with higher level of HBsAg at day-1 after TAC(β=-0.225, P=0.091 ).⑤The increase of ALT and AST levels at day-1 after TAC are significant higher in TP53 Arg/Arg carries than that in Arg/Pro carries, and significant higher in TP53 Arg/Pro carries than that in Pro/Pro carries (δALT¹:β=0.363, P=0.056;δAST¹:β=0.451, P=0.019) .â‘¥The increase of ALT level at day-1 after TAC is significant higher in hOGG1 Cys/Cys carries than that in non-Cys/Cys carries(β=0.520,P=0.067).Conclusions1,hOGG1 Cys326Ser: The Ser allele carriers revealed severe liver damage after TAC therapy than that in the Cys carriers.2,TP53 Arg72Pro: The Arg allele carriers possibly revealed severe liver damage after TAC therapy than that in the Pro carriers.3,p21^WAF-1/CIP-1Ser31Arg: The Ser allele carriers revealed severe liver damage after TAC therapy than that in the Arg carriers.