Relationship of XRCC1,PARP1 and APE1 polymorphisms with efficacy of platinum-based chemotherapy for patients with advanced non-small cell lung cancer
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    Abstract:

    Objective:To investigate the relationship of X-ray repair cross complement gene 1(XRCC1), poly (ADP-ribose)polymerase-1(PARP1) and apurinic/apyrimidinic endonuclease 1(APE1) polymorphisms with the efficacy of platinum-based chemotherapy for treatment of the patients with advanced non-small-cell lung cancer(NSCLC). Methods: A total of 151 patients with advanced NSCLC were routinely treated with platinum-based chemotherapy, and their clinical responses were evaluated. XRCC1 G28152A (Arg399Gln), XRCC1 C26304T (Arg194Trp), PARP1 T2444C (Val762Ala) and APE1 T1349G (Asp148Glu) of the patients were genotyped using the TaqMan method. The association of these polymorphisms with the clinical responses was analyzed using unconditional logistic regression model. Results:XRCC1 G28152A polymorphism was significantly correlated with clinical benefit. The efficacy of chemotherapy of XRCC1 28152 GA genotype carriers significantly increased compared with patients with GG genotype(adjusted OR=2.85, 95%CI:1.291~6.277, P < 0.05). Patients carrying XRCC1 28152 A allele(GA/AA) had better clinical response than patients with wildtype allele (adjusted OR=2.48,95%CI:1.330~6.075, P < 0.05). Compared with CC and CT genotypes, XRCC1 26304 TT genotype carriers had a roughly 64% decreased efficiency but with no statistical significance (adjusted OR=0.36,95%CI:0.040~3.298). A similar result was found in polymorphism of PARP1 T2444C,the response rate of chemotherapy of the patients with CC genotype significantly decreased compared with other (adjusted OR = 0.37, 95%CI:0.118~1.170). No significant association was found between APE1 T1349G polymorphism with clinical response. Conclusion: The XRCC1 G28152A (Arg399Gln) polymorphism is significantly associated with the clinical benefit of NSCLC patients receiving platinum-based chemotherapy, and the XRCC1 G28152A genotypes detected by TaqMan method may be useful in clinical applications to predict the sensitivity of chemotherapy in NSCLC patients.

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赵 万,胡铃敏,王 铖,朱婷婷,魏 娟,胡志斌,殷咏梅. XRCC1?PARP1和APE1多态性与晚期非小细胞肺癌铂类药物化疗敏感性的关系[J].南京医科大学学报(自然科学版英文版),2011,(7):1021-1026.

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  • Received:February 09,2011
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