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


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.


CONCLUSIONS
DNA damage as measured by the comet assay is associated with the development of multiple primary tumors in individuals with NSCLC.
Orlow
Irene
I
Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. orlowi@mskcc.org
Park
Bernard J
BJ
Mujumdar
Urvi
U
Patel
Himali
H
Siu-Lau
Puiki
P
Clas
Brian A
BA
Downey
Robert
R
Flores
Raja
R
Bains
Manjit
M
Rizk
Nabil
N
Dominguez
Gemma
G
Jani
Jen
J
Berwick
Marianne
M
Begg
Colin B
CB
Kris
Mark G
MG
Rusch
Valerie W
VW
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000633:toxicity; D000368:Aged; D002273:Carcinogens / Q000633:toxicity; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D020552:Comet Assay; D018736:DNA Adducts; D004249:DNA Damage; D004260:DNA Repair; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary / Q000235:genetics*
D002273:Carcinogens; D018736:DNA Adducts; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide