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Effect of the XRCC1 and XRCC3 Genetic Polymorphisms on the Efficacy of Platinum-based Chemotherapy in Patients with Advanced Non-small Cell Lung Cancer

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Author(s): Chong’an XU | Xiaojie WANG | Ye ZHANG | Lin LI

Journal: Chinese Journal of Lung Cancer
ISSN 1009-3419

Volume: 14;
Issue: 12;
Start page: 912;
Date: 2011;
Original page

Keywords: Lung neoplasms | X-ray repair cross complementing protein 1 (XRCC1) | X-ray repair cross complementing protein 3 (XRCC3) | Single nucleotick polymorphism | Chemotherapy sensitivity

ABSTRACT
Background and objective DNA repair gene polymorphisms can be used to predict the sensitivity of platinum-based chemotherapy. Thus, such polymorphisms are important for the individual treatment of non-small cell lung cancer (NSCLC). The aim of this study is to investigate the relationship between X-ray repair cross complementing protein 1 (XRCC1) and X-ray repair cross complementing protein 3 (XRCC3) gene polymorphisms and the chemosensitivity of platinum-based chemotherapy in patients with advanced NSCLC. Methods Genomic DNA were extracted from the sera of a total of 130 patients with advanced NSCLC who received platinum-based chemotherapy. XRCC1 Arg194 Trp, Arg399 Gln, and XRCC3 Thr241 Met were genotyped using the polymerase chain reaction-restriction fragment length polymorphism method, and the relationship between XRCC1 and XRCC3 polymorphisms and chemotherapy sensitivity was analyzed. Results A total of 130 patients with advanced NSCLC received platinum-based chemotherapy, with an overall response rate of 33.8% after two chemotherapy cycles. The XRCC1 194 and 399 genetic polymorphisms, but not XRCC3 241, were found to be related to the chemosensitivity. The objective response rate of the patients with at least one XRCC1 194 Trp allele was 2.5 times higher than that of Arg/Arg genotype carriers (42.1% vs 22.2%, OR=2.545, 95%CI: 1.159-5.590, P=0.020). The objective response rate of the XRCC1 399 Arg/Arg genotype carriers was significantly higher than that of the patients with at least one Gln allele (45.5% vs 21.9%, OR=0.336, 95%CI: 0.156-0.722, P=0.005). Combined effects between XRCC1 194 and XRCC1 399 were observed. The objective response rate of the patients with at least one XRCC1 194 Trp allele and a 399 Arg/Arg genotype was significantly higher than that of patients with 194 Arg/Arg and 399 Arg/Gln genotypes (44.4% vs 18.8%, OR=3.467, 95%CI: 1.223-9.782, P=0.019). Moreover, XRCC1 and XRCC3 have a combined effect in predicting chemosensitivity. Patients with XRCC3 241 Thr/Met, 399 Arg/Arg, and at least one XRCC1 194 Trp allele simultaneously showed an improved objective response rate. Conclusion The combination of the XRCC1 and XRCC3 polymorphisms may be associated with patient sensitivity to platinum-based chemotherapy in advanced NSCLC.
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