Prospective assessment of XRCC3, XPD and Aurora kinase A single-nucleotide polymorphisms in advanced lung cancer
Prospective assessment of XRCC3, XPD and Aurora kinase A single-nucleotide polymorphisms in advanced lung cancer
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DOI：
10.1007/s00280-012-1985-9
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发表时间：
2012-12-01
影响因子：
3
通讯作者：
Rosell, R.
中科院分区：
文献类型：
--
作者：
Provencio, M.;Camps, C.;Rosell, R.
新的治疗方法正在开发的基础上，发现几个遗传异常的基础上非小细胞肺癌（NSCLC）可以影响化疗敏感性。因此，分子标记物的鉴定，对肺癌的治疗决策有用，对疾病管理至关重要。本研究评估了XRCC 3、XPD和Aurora激酶A在NSCLC患者中的单核苷酸多态性（SNP），以评估这些生物标志物是否能够预测患者的预后。符合条件的患者患有组织学证实的IV期或IIIB期（伴恶性胸腔积液）NSCLC，既往未接受过化疗，世界卫生组织体能状态（PS）评分为0-1。患者在第1天和第8天接受长春瑞滨25 mg/m2静脉给药，第1天接受顺铂75 mg/m2静脉给药，每21天一次，最多6个周期。从每个人收集静脉血，并分离基因组DNA。对180例患者进行XRCC 3 T241 M、XPD K751 Q、XPD D312 N、AURORA 91、AURORA 169位点的SNPs检测。中位年龄为62岁; 87%为男性; 34%为PS 0; 83%为IV期疾病。中位周期数为4个。至进展时间为5.1个月（95% CI，4.2-5.9）。总体中位生存期为8.6个月（95% CI，7.1-10.1）。XRCC 3 T241 M、XPD K751 Q、XPD D312 N、AURORA 91、AURORA 169的SNP与化疗疗效和毒性无显著相关性，提示XRCC 3、XPD或Aurora激酶A的SNP不能预测含铂化疗的晚期NSCLC患者的疗效。
New therapeutic approaches are being developed based on findings that several genetic abnormalities underlying non-small-cell lung cancer (NSCLC) can influence chemosensitivity. The identification of molecular markers, useful for therapeutic decisions in lung cancer, is thus crucial for disease management. The present study evaluated single-nucleotide polymorphisms (SNPs) in XRCC3, XPD and Aurora kinase A in NSCLC patients in order to assess whether these biomarkers were able to predict the outcomes of the patients.The Spanish Lung Cancer Group prospectively assessed this clinical study. Eligible patients had histologically confirmed stage IV or IIIB (with malignant pleural effusion) NSCLC, which had not previously been treated with chemotherapy, and a World Health Organization performance status (PS) of 0-1. Patients received intravenous doses of vinorelbine 25 mg/m(2) on days 1 and 8, and cisplatin 75 mg/m(2) on day 1, every 21 days for a maximum of 6 cycles. Venous blood was collected from each, and genomic DNA was isolated. SNPs in XRCC3 T241M, XPD K751Q, XPD D312N, AURORA 91, AURORA 169 were assessed.The study included 180 patients. Median age was 62 years; 87 % were male; 34 % had PS 0; and 83 % had stage IV disease. The median number of cycles was 4. Time to progression was 5.1 months (95 % CI, 4.2-5.9). Overall median survival was 8.6 months (95 % CI, 7.1-10.1). There was no significant association between SNPs in XRCC3 T241M, XPD K751Q, XPD D312N, AURORA 91, AURORA 169 in outcome or toxicity.Our findings indicate that SNPs in XRCC3, XPD or Aurora kinase A cannot predict outcomes in advanced NSCLC patients treated with platinum-based chemotherapy.