Risk assessment of renal cell carcinoma using alkaline comet assay.

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.