Genetic instability in bladder cancer assessed by the comet assay

Background: Latent genetic instability has been associated with an increased risk for several cancers. We used the comet assay (single-cell gel electrophoresis) to assess whether genetic instability, as reflected by susceptibility to DNA damage, was associated with the risk of bladder cancer in a case-control study. Methods: We used the comet assay to measure baseline and benzo[a]pyrene diol epoxide (BPDE)and gamma-radiation-induced DNA damage in individual peripheral blood lymphocytes from 114 incident case patients with bladder cancer and 145 matched healthy control subjects. All subjects provided personal information, including smoking history. DNA damage was visualized with the comet assay and quantified by the Olive tail moment parameter, a relative measure. Multivariable analysis was used to assess relative risks for bladder cancer associated with DNA damage. All statistical tests were two-sided. Results: Baseline levels of DNA damage were statistically significantly higher in case patients (tail moment = 1.40) than in control subjects (tail moment = 1.21) (difference = 0.19, 95% confidence interval [CI] = 0.04 to 0.32; P = .015), as were gamma-radiation-induced (tail moment = 4.76 versus 4.22; difference = 0.54, 95% CI = 0.11 to 0.96; P = .013) and BPDE-induced (tail moment = 4.06 versus 3.45; difference = 0.61, 95% CI = 0.23 to 0.99; P = .002) DNA damage. When data were dichotomized at the median value for DNA damage in control subjects and adjusted for age, sex, ethnicity, and smoking status, an increased estimated relative risk of bladder cancer was statistically significantly associated with DNA damage at baseline (odds ratio [OR] = 1.84, 95% CI = 1.07 to 3.15) and after gamma-radiation (OR = 1.81, 95% CI = 1.04 to 3.14) but not after BPDE treatment (OR = 1.69, 95% CI = 0.98 to 2.93). Conclusion: Latent genetic instability as measured by the comet assay is associated with an increased estimated relative risk of bladder cancer. [J Nad Cancer Inst 2003;95: 540-7]