[XRCC1和XRCC3基因多态性对晚期非小细胞肺癌患者铂类化疗疗效的影响]
[Effect of the XRCC1 and XRCC3 genetic polymorphisms on the efficacy of platinum-based chemotherapy in patients with advanced non-small cell lung cancer].
作者信息
Xu Chong'an, Wang Xiaojie, Zhang Ye, Li Lin
机构信息
Department of Medical Oncology, the Fourth Affiliated Hospital, China Medical University, Shenyang 110032, China.
出版信息
Zhongguo Fei Ai Za Zhi. 2011 Dec;14(12):912-7. doi: 10.3779/j.issn.1009-3419.2011.12.03.
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.
CONCLUSIONS
The combination of the XRCC1 and XRCC3 polymorphisms may be associated with patient sensitivity to platinum-based chemotherapy in advanced NSCLC.
背景与目的
DNA修复基因多态性可用于预测铂类化疗的敏感性。因此，此类多态性对非小细胞肺癌（NSCLC）的个体化治疗具有重要意义。本研究旨在探讨X射线修复交叉互补蛋白1（XRCC1）和X射线修复交叉互补蛋白3（XRCC3）基因多态性与晚期NSCLC患者铂类化疗敏感性之间的关系。
方法
从130例接受铂类化疗的晚期NSCLC患者的血清中提取基因组DNA。采用聚合酶链反应-限制性片段长度多态性方法对XRCC1 Arg194 Trp、Arg399 Gln和XRCC3 Thr241 Met进行基因分型，并分析XRCC1和XRCC3多态性与化疗敏感性之间的关系。
结果
130例晚期NSCLC患者接受了铂类化疗，两个化疗周期后的总缓解率为33.8%。发现XRCC1 194和399基因多态性与化疗敏感性相关，而XRCC3 241基因多态性与化疗敏感性无关。至少携带一个XRCC1 194 Trp等位基因的患者的客观缓解率比Arg/Arg基因型携带者高2.5倍（42.1%对22.2%，OR=2.545，95%CI：1.159-5.590，P=0.020）。XRCC1 399 Arg/Arg基因型携带者的客观缓解率显著高于至少携带一个Gln等位基因的患者（45.5%对21.9%，OR=0.336，95%CI：0.156-0.722，P=0.005）。观察到XRCC1 194和XRCC1 399之间存在联合效应。至少携带一个XRCC1 194 Trp等位基因且399为Arg/Arg基因型的患者的客观缓解率显著高于194为Arg/Arg且399为Arg/Gln基因型的患者（44.4%对18.8%，OR=3.467，95%CI：1.223-9.782，P=0.019）。此外，XRCC1和XRCC3在预测化疗敏感性方面具有联合效应。同时具有XRCC3 241 Thr/Met、399 Arg/Arg和至少一个XRCC1 194 Trp等位基因的患者的客观缓解率有所提高。
结论
XRCC1和XRCC3多态性的联合可能与晚期NSCLC患者对铂类化疗的敏感性相关。
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