title: DNA damage phenotype and prostate cancer risk.
abstract: The capacity of an individual to process DNA damage is considered a crucial factor in carcinogenesis. The comet assay is a phenotypic measure of the combined effects of sensitivity to a mutagen exposure and repair capacity. In this paper, we evaluate the association of the DNA repair kinetics, as measured by the comet assay, with prostate cancer risk. In a pilot study of 55 men with prostate cancer, 53 men without the disease, and 71 men free of cancer at biopsy, we investigated the association of DNA damage with prostate cancer risk at early (0-15 min) and later (15-45 min) stages following gamma-radiation exposure. Although residual damage within 45 min was the same for all groups (65% of DNA in comet tail disappeared), prostate cancer cases had a slower first phase (38% vs. 41%) and faster second phase (27% vs. 22%) of the repair response compared to controls. When subjects were categorized into quartiles, according to efficiency of repairing DNA damage, high repair-efficiency within the first 15 min after exposure was not associated with prostate cancer risk while higher at the 15-45 min period was associated with increased risk (OR for highest-to-lowest quartiles=3.24, 95% CI=0.98-10.66, p-trend=0.04). Despite limited sample size, our data suggest that DNA repair kinetics marginally differ between prostate cancer cases and controls. This small difference could be associated with differential responses to DNA damage among susceptible individuals.
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
authors.forename: O
authors.initials: O
authors.lastname: Kosti
authors.forename: L
authors.initials: L
authors.lastname: Goldman
authors.forename: D T
authors.initials: DT
authors.lastname: Saha
authors.forename: R A
authors.initials: RA
authors.lastname: Orden
authors.forename: A J
authors.initials: AJ
authors.lastname: Pollock
authors.forename: H L
authors.initials: HL
authors.lastname: Madej
authors.forename: A W
authors.initials: AW
authors.lastname: Hsing
authors.forename: L W
authors.initials: LW
authors.lastname: Chu
authors.forename: J H
authors.initials: JH
authors.lastname: Lynch
authors.forename: R
authors.initials: R
authors.lastname: Goldman
mesh_terms: D000368:Aged; D001706:Biopsy; D020552:Comet Assay; D004249:DNA Damage; D004260:DNA Repair / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009381:Neoplasms, Radiation-Induced / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D010865:Pilot Projects; D011467:Prostate / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D018570:Risk Assessment; D012307:Risk Factors