An analysis of DNA repair as a determinant of survival in patients with non-small-cell lung cancer.
An analysis of DNA repair as a determinant of survival in patients with non-small-cell lung cancer.
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DOI：
10.1093/jnci/94.14.1091
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发表时间：
2002-07
期刊：
影响因子：
--
通讯作者：
C. Bosken;Q. Wei;C. Amos;M. Spitz
中科院分区：
文献类型：
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作者：
C. Bosken;Q. Wei;C. Amos;M. Spitz
背景非小细胞肺癌（NSCLC）经常对化疗产生耐药性，这种耐药性与肿瘤组织中核苷酸切除修复（NER）的升高有关。我们假设，具有有效全身（宿主）NER 的 NSCLC 患者的生存率比 NER 次优的患者要差，并且 NER 有效性与生存之间的关联在接受化疗的患者中最为明显。方法 1995 年 7 月至 1999 年 12 月期间，对 375 名新诊断的 NSCLC 患者进行了病例对照研究。NER 活性通过宿主细胞再激活测定在患者外周淋巴细胞中测量的 DNA 修复能力 (DRC) 进行估计。 Cox 比例风险模型用于评估 DRC 与生存之间的关联。所有统计检验都是双面的。结果 对于 DRC 每增加一个单位（百分比），对于 345 名可获得体重减轻信息的患者，死亡相对风险 (RR) 为 1.05（95% 置信区间 [CI] = 1.00 至 1.10；P =.05）；对于 275 名拥有完整随访信息的患者，死亡相对风险 (RR) 为 1.06（95% CI = 1.00 至 1.12；P =.03）。在 86 名仅接受化疗的患者中，DRC 每增加一个单位（百分比），死亡 RR 增加至 1.11（95% CI = 1.02 至 1.21；P =.01）。在这 86 名患者中，位于 DRC 分布最高四分位数的患者的死亡 RR 是最低四分位数患者的两倍（RR = 2.72；95% CI = 1.24 至 5.95；P = 0.01）。有效的 DRC 并不是未接受化疗的患者死亡的危险因素。结论 我们的数据表明，有效的宿主 DRC 可能与接受化疗的 NSCLC 患者较差的生存率相关。
BACKGROUND Non-small-cell lung cancer (NSCLC) is frequently resistant to chemotherapy, and this resistance has been associated with elevated nucleotide excision repair (NER) in tumor tissue. We hypothesized that patients with NSCLC who had effective systemic (host) NER would have poorer survival than patients with suboptimal NER and that the association between NER effectiveness and survival would be most marked in patients receiving chemotherapy. METHODS 375 patients with newly diagnosed NSCLC were accrued for a case-control study between July 1995 and December 1999. NER activity was estimated as the DNA repair capacity (DRC) measured in the patient's peripheral lymphocytes by the host cell reactivation assay. Cox proportional hazards models were used to assess the association between DRC and survival. All statistical tests were two-sided. RESULTS For every unit (percentage) increase in DRC, the relative risk (RR) of death was 1.05 (95% confidence interval [CI] = 1.00 to 1.10; P =.05) for the 345 patients for whom weight loss information was available and 1.06 (95% CI = 1.00 to 1.12; P =.03) for the 275 patients with complete follow-up information. In 86 patients treated with chemotherapy only, the RR of death increased to 1.11 (95% CI = 1.02 to 1.21; P =.01) for every unit (percentage) increase in DRC. Of those 86 patients, patients in the top quartile of the DRC distribution were at twice the RR of death as those in the lowest quartile (RR = 2.72; 95% CI = 1.24 to 5.95; P =.01). Effective DRC was not a risk factor for death in patients who were not treated with chemotherapy. CONCLUSIONS Our data suggest that effective host DRC may be associated with poorer survival in patients with NSCLC who are treated with chemotherapy.