DNA Damage and Repair Capacity in Patients With Lung Cancer: Prediction of Multiple Primary Tumors

Author:

Orlow Irene1,Park Bernard J.1,Mujumdar Urvi1,Patel Himali1,Siu-Lau Puiki1,Clas Brian A.1,Downey Robert1,Flores Raja1,Bains Manjit1,Rizk Nabil1,Dominguez Gemma1,Jani Jen1,Berwick Marianne1,Begg Colin B.1,Kris Mark G.1,Rusch Valerie W.1

Affiliation:

1. From the Departments of Epidemiology and Biostatistics, Surgery, and Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY; and the University of New Mexico, Albuquerque, NM

Abstract

PurposePatients 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 MethodsOne 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.ResultsConstitutive 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.ConclusionDNA damage as measured by the comet assay is associated with the development of multiple primary tumors in individuals with NSCLC.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

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