Risk assessment of renal cell carcinoma using alkaline comet assay

Abstract

Background: DNA damage induced by mutagens has been associated with an individual's susceptibility to cancer.

Methods: In the current study, which involved 193 renal cell carcinoma (RCC) patients and 193 controls, DNA damage before mutagen induction (baseline), after benzo(alpha)pyrene dio epoxide (BPDE) treatment, and after gamma-radiation induction were assayed by comet assay in peripheral blood lymphocytes. Olive tail moments were used as DNA damage parameters. The 5 variables that were analyzed for their associations with RCC risk were baseline, BPDE-induced, gamma-radiation-induced, net BPDE-induced (BPDE-induced subtract baseline), and net gamma-radiation-induced (gamma-radiation-induced subtract baseline) Olive tail moments.

Results: Significantly higher Olive tail moments were observed in cases compared with controls at baseline (1.95 vs 1.65; P = .008), after BPDE induction (3.10 vs 2.38; P < .001), and after gamma-radiation induction (4.25 vs 3.47; P < .001). The net BPDE-induced and gamma-radiation-induced DNA damage was also found to be significantly higher in cases compared with controls (P < .001 for both mutagens). Using the 75th percentile Olive tail moments in the controls as the cutoff point, the authors found that high levels of baseline DNA damage, BPDE-induced DNA damage, and gamma-radiation-induced DNA damage were associated with significantly increased risks of RCC, with odds ratios of 1.96 (95% confidence interval [95% CI], 1.26-3.06), 2.70 (95% CI, 1.72-4.23), and 3.13 (95% CI, 1.99-4.92), respectively. Similarly, net BPDE-induced and net gamma-radiation-induced DNA damages were also found to be significantly associated with elevated risks of RCC.

Conclusions: The results of the current study suggest that both baseline and mutagen-induced DNA damages assessed by comet assay are associated with an increased risk of RCC.