Genetic Variants of NBS1 Predict Clinical Outcome of Platinum-based Chemotherapy in Advanced Non-small Cell Lung Cancer in Chinese
Genetic Variants of NBS1 Predict Clinical Outcome of Platinum-based Chemotherapy in Advanced Non-small Cell Lung Cancer in Chinese
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DOI：
10.7314/apjcp.2012.13.3.851
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发表时间：
2012-01-01
影响因子：
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通讯作者：
Shu, Yong-Qian
中科院分区：
文献类型：
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作者：
Xu, Jia-Li;Hu, Ling-Min;Shu, Yong-Qian
目的：NBS 1在DNA双链断裂（DSB）修复中起关键作用。我们进行这项研究是为了研究NBS 1中的两个关键多态性（rs 1805794和rs 13312840）对接受铂类化疗的晚期非小细胞肺癌（NSCLC）患者的治疗反应和预后的影响。方法：采用TaqMan方法，对147例NSCLC患者进行基因分型。采用logistic回归分析计算比值比（OR）及其95%置信区间（CI），作为铂类化疗反应率差异的衡量指标。采用Kaplan-Meier和对数秩检验评估无进展生存期（PFS）和总生存期（OS）的差异。采用考克斯比例风险模型评估PFS和OS的风险比（HR）。然而，与GG基因型相比，携带rs 1805794 CC变异基因型的患者的PFS显著改善（16.0 vs. 8.0个月，P = 0.040）。多变量考克斯回归分析进一步显示rs 1805974是PFS的显著有利预后因素[CC/CG vs. GG：校正HR = 0.62，95% CI：0.39-0.99; CC vs. CG/GG：校正HR = 0.56，95% CI：0.32-0.97]。同样，样本量较小的rs 13312840也显示与PFS显著相关（CC vs. CT/TT：校正HR = 25.62，95% CI：1.53-428.39）。结论：我们的研究结果表明，NBS 1基因多态性可能是中国人群中NSCLC预后的遗传生物标志物，尤其是铂类药物化疗的PFS。
Objective: NBS1 plays a key role in the repair of DNA double-strand break (DSB). We conducted this study to investigate the effect of two critical polymorphisms (rs1805794 and rs13312840) in NBS1 on treatment response and prognosis of advanced non-small cell lung cancer (NSCLC) patients with platinum-based chemotherapy. Methods: Using TaqMan methods, we genotyped the two polymorphisms in 147 NSCLC patients. Odds ratios (ORs) and their 95% confidential intervals (CIs) were calculated as a measure of difference in the response rate of platinum-based chemotherapy using logistic regression analysis. The Kaplan-Meier and log-rank tests were used to assess the differences in progression-free survival (PFS) and overall survival (OS). Cox proportional hazards model was applied to assess the hazard ratios (HRs) for PFS and OS. Results: Neither of the two polymorphisms was significantly associated with treatment response of platinum-based chemotherapy. However, patients carrying the rs1805794 CC variant genotype had a significantly improved PFS compared to those with GG genotype (16.0 vs. 8.0 months, P = 0.040). Multivariable cox regression analysis further showed that rs1805974 was a significantly favorable prognostic factor for PFS [CC/CG vs. GG: Adjusted HR = 0.62, 95% CI: 0.39-0.99; CC vs. CG/GG: Adjusted HR = 0.56, 95% CI: 0.32-0.97). Similarly, rs13312840 with a small sample size also showed a significant association with PFS (CC vs. CT/TT: Adjusted HR = 25.62, 95% CI: 1.53-428.39). Conclusions: Our findings suggest that NBS1 polymorphisms may be genetic biomarkers for NSCLC prognosis especially PFS with platinum-based chemotherapy in the Chinese population.