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. 2008 Jul 20;26(21):3560-6.
doi: 10.1200/JCO.2007.13.2654.

DNA damage and repair capacity in patients with lung cancer: prediction of multiple primary tumors

Irene Orlow  1 , Bernard J Park, Urvi Mujumdar, Himali Patel, Puiki Siu-Lau, Brian A Clas, Robert Downey, Raja Flores, Manjit Bains, Nabil Rizk, Gemma Dominguez, Jen Jani, Marianne Berwick, Colin B Begg, Mark G Kris, Valerie W Rusch
Affiliations

DNA damage and repair capacity in patients with lung cancer: prediction of multiple primary tumors

Irene Orlow et al. J Clin Oncol. .

Abstract

Purpose: 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).

Patients and methods: 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.

Results: 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.

Conclusion: DNA damage as measured by the comet assay is associated with the development of multiple primary tumors in individuals with NSCLC.

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Figures

Figure 1
Figure 1
(A) Constitutive, (B) BPDE-induced, and (C) unrepaired DNA damage in patients with NSCLC. Left: bar graphs show the distribution of DNA damage among patients with single (green) and multiple (blue) primary tumors. Right: representative nucleoids and median TI values obtained with the comet assay (200×). Note the extent and intensity of the tails in cases 16 and 21 (arrows).
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