Study Of The Relationship Between XRCC1 Polymorphism And Efficacy Of Oxaliplatin Chemotherapy In Patients With CRC Liver Metastasis

Objective:To investigate the association between genetic polymor-phisms of XRCC1 Ar9399Gln and efficacy of oxaliplatin chemotherapy in patients with CRC liver metastasis.Methods:Forty-six histologically confirmed patients with CRC liver metastasis were recruited in the study. All the patients were treated with chemotherapy (oxaliplatin+ftorafur+calcium folinate), chemotherapy was performed for three times at least. DNA was extracted from cancer tissues, then pyrosequencing method were applied to detect the genotypes of XRCC1. The differences of response to chemotherapy, progression-free survival(PFS),adverse events associated with chemo-therapy,karnofsky performance status(KPS) score and carcinoembryonic antigen(CEA) level betwwen the genotypes were analyzed by statistical methods.Result:1. XRCC1Arg399Gln presented three genotypes, the frequency of genotypes were:G/G 54.4%, G/A 32.6% and A/A 13.0%,respectively.2. The overall disease control rate (CR+PR+SD) of forty-six patients was 54.3% after chemotherapy, G/G genotype was 68.0% and G/A+A/A genotype was 38.1%, respectively. There were significant difference between the two genotypes(P<0.05).3. The rate of stability and improvement with KPS score in G/G genotype was 76.0%, and G/A+A/A genotype was 47.6%. There were significant difference between the two genotypes(P<0.05). 4. The rate of decline and negative with CEA level in G/G genotype was 47.6%, and G/A+A/A genotype was 17.6%. There were significant difference between the two genotypes(P<0.05).5. The median PFS of 46 patients was 28 weeks, G/G genotype was 32 weeks and G/A+A/A genotype was 23 weeks respectively, there were significant difference between the two genotypes(P<0.05). COX regression model found that PFS only had a relationship with genotypes(OR=2.543,95%CI=1.472-4.036, P<0.05), there were no relationships with age, gender, tumor site, pathology,KPS score and CEA level (P>0.05).Conclusion:XRCC1Arg399Gln genetic polymorphisms may be associated with the clinical response and PFS in patients with CRC liver metastasis after oxaliplatin chemotherapy. XRCC1Arg399Gln polymor-phisms may be used as a valuable gene predictive factor for efficacy of oxaliplatin in patients with CRC liver metastasis.