Orlow Irene, Park Bernard J, Mujumdar Urvi, Patel Himali, Siu-Lau Puiki, Clas Brian A, Downey Robert, Flores Raja, Bains Manjit, Rizk Nabil, Dominguez Gemma, Jani Jen, Berwick Marianne, Begg Colin B, Kris Mark G, Rusch Valerie W
Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
J Clin Oncol. 2008 Jul 20;26(21):3560-6. doi: 10.1200/JCO.2007.13.2654.
Patients who survive one occurrence of 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 NSCLCs (cases) and compared the results to those obtained in patients with a single NSCLC (controls).
One hundred eight cases and 99 controls matched by age, sex, 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 and the tail intensity as measures to assess baseline damage, induced damage and repair capacity.
Constitutive DNA damage, benzo(a)pyrene diol epoxide-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.
非小细胞肺癌（NSCLC）患者若经历一次发病后存活下来，发生第二种恶性肿瘤的风险会更高。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（病例组）的固有和诱导性DNA损伤及修复能力，并将结果与单发性NSCLC患者（对照组）的结果进行比较。
研究了108例病例组和99例按年龄、性别及确诊时间匹配的对照组。在将外周血淋巴细胞暴露于烟草衍生致癌物前后，通过彗星试验评估DNA损伤，使用尾矩和尾强度作为评估基线损伤、诱导损伤及修复能力的指标。
病例组的固有DNA损伤、苯并（a）芘二醇环氧化物诱导的损伤以及BPDE诱导损伤后的修复均显著高于对照组。在针对潜在混杂因素进行调整的回归分析中，这些结果得到了证实。
通过彗星试验测量的DNA损伤与NSCLC个体中多发性原发性肿瘤的发生有关。
