DNA damage and repair capacity in patients with lung cancer: prediction of multiple primary tumors.
DNA damage and repair capacity in patients with lung cancer: prediction of multiple primary tumors.
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DOI：
10.1200/jco.2007.13.2654
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发表时间：
2008-07-20
期刊：
影响因子：
--
通讯作者：
Rusch VW
中科院分区：
文献类型：
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作者：
Orlow I;Park BJ;Mujumdar U;Patel H;Siu-Lau P;Clas BA;Downey R;Flores R;Bains M;Rizk N;Dominguez G;Jani J;Berwick M;Begg CB;Kris MG;Rusch VW
存活一例非小细胞肺癌(NSCLC)的患者患第二种恶性肿瘤的风险更高。修复受损DNA的能力可能会调节个体患肺癌的易感性。因此，我们评估了多发性NSCLC患者(病例)的结构性和诱发性DNA损伤以及修复能力，并将结果与单一NSCLC患者(对照组)的结果进行了比较。研究对象为年龄、性别、发病时间相匹配的108例患者和99例对照。用尾矩(TM)和尾部强度(TI)作为评估基线损伤、诱导损伤和修复能力的指标，用彗星试验评估细胞暴露于烟草致癌物前后的外周血淋巴细胞DNA损伤。病例组的结构性DNA损伤、BPDE诱导的损伤和BPDE诱导的损伤后的修复均显著高于对照组。这些结果在调整了潜在混杂因素的回归分析中得到了证实。彗星试验测定的DNA损伤与非小细胞肺癌患者多原发肿瘤的发生有关。
Patients who survive one non-small cell lung cancer (NSCLC) are at higher risk of a second malignancy. Capacity to repair damaged DNA may modulate individual susceptibility to develop lung cancer. Therefore, we evaluated constitutive and induced DNA damage, and repair capacity, in patients with multiple NSCLC (cases) and compared the results to those obtained in patients with single NSCLC (controls). One-hundred and eight cases and 99 controls matched by age, gender and time since diagnosis were studied. DNA damage was assessed on peripheral blood lymphocytes by the comet assay before and after exposing cells to a tobacco-derived carcinogen, using the tail moment (TM), and the tail intensity (TI) as measures to assess baseline damage, induced damage and repair capacity. Constitutive DNA damage, BPDE-induced damage, and repair after BPDE-induced damage were all significantly higher in cases than in controls. These results were confirmed in regression analyses adjusted for potential confounders. DNA damage as measured by the comet assay is associated with the development of multiple primary tumors in individuals with NSCLC.