XPD and XRCC1 genetic polymorphisms are prognostic factors in advanced non-small-cell lung cancer patients treated with platinum chemotherapy
XPD and XRCC1 genetic polymorphisms are prognostic factors in advanced non-small-cell lung cancer patients treated with platinum chemotherapy
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DOI：
10.1200/jco.2004.08.067
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发表时间：
2004-07-01
影响因子：
45.3
通讯作者：
Christiani, DC
中科院分区：
文献类型：
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作者：
Gurubhagavatula, S;Liu, G;Christiani, DC
目的 铂剂会导致 DNA 交联和氧化损伤。 DNA 修复基因的遗传多态性与差异性 DNA 修复活性相关，可能解释铂类药物治疗非小细胞肺癌 (NSCLC) 后总生存期的个体间差异。方法我们使用聚合酶链反应-限制性片段长度多态性来评估 XPD (Asp312Asn) 和 XRCC1 的遗传多态性 (Arg399Gln) 103 例接受铂类化疗的 III 期 (54%) 和 IV 期 (46%) NSCLC 患者的 DNA 修复基因。 结果 中位年龄为 58 岁（范围为 32 至 77 岁），49% 为女性，死亡 86 例。中位随访期为 61.9 个月。中位生存时间（MST）为14.9个月；按阶段划分，MST 为 28.6 个月（IIIA）、16.0 个月（IIIB）和 9.3 个月（IV）。基因型与阶段无关。 XPD 或 XRCC1 变异等位基因数量的增加与总生存期缩短相关（通过对数秩检验，分别为 P = .003 和 P = .07）。同样，当我们比较两种多态性的变异等位基因组合时，我们发现更多数量的变异等位基因与总体生存率降低相关（P = .009，对数秩检验）。即使考虑到分期、体能状态和化疗方案，这些多态性也可以独立预测总生存期。结论 XPD 和 XRCC1 的遗传多态性可能是铂类治疗晚期 NSCLC 患者的重要预后因素。 (C) 2004 年，美国临床肿瘤学会。
Purpose Platinum agents cause DNA cross-linking and oxidative damage. Genetic polymorphisms of DNA repair genes are associated with differential DNA repair activity and may explain interindividual differences in overall survival after therapy with platinum agents for non-small-cell lung cancer (NSCLC).Methods We used polymerase chain reaction-restriction fragment length polymorphism to evaluate genetic polymorphisms of the XPD (Asp312Asn) and XRCC1 (Arg399Gln) DNA repair genes in 103 patients with stage III (54%) and IV (46%) NSCLC treated with platinum-based chemotherapy.Results Median age was 58 years (range, 32 to 77 years), 49% were females, and there were 86 deaths. Median follow-up period was 61.9 months. Median survival time (MST) was 14.9 months; by stage, MST was 28.6 months (IIIA), 16.0 months (IIIB), and 9.3 months (IV). Genotypes were not associated with stage. Increasing numbers of either XPD or XRCC1 variant alleles were associated with shorter overall survival (P = .003 and P = .07, respectively, by log-rank test). Similarly, when we compared combinations of variant alleles across both polymorphisms, we found that a greater number of variant alleles was associated with decreasing overall survival (P = .009, log-rank test). These polymorphisms independently predicted overall survival even after taking into account stage, performance status, and chemotherapy regimen.Conclusion Genetic polymorphisms in XPD and XRCC1 may be important prognostic factors in platinum-treated patients with advanced NSCLC. (C) 2004 by American Society of Clinical Oncology.