Predictors of esophageal cancer risk: assessment of susceptibility to DNA damage using comet assay

Individuals' susceptibility to DNA damage could be identified by mutagen-challenged assays. We tested the hypothesis that susceptibility to DNA damage, measured by comet assay, may be associated with increased esophageal cancer (EC) risk. We recruited 102 subjects with previously untreated EC and 112 healthy controls. Baseline (untreated), benzo[a]pyrene diol epoxide (BPDE)-induced, and gamma-radiation-induced DNA damage were quantified by the Olive tail moment parameter. The mean tail moment was significantly higher in cases than in controls at baseline (case vs. control: 2.6 vs. 1.9, P < 0.01), after BPDE induction (case vs. control: 3.8 vs. 2.7, P < 0.01), and after gamma-radiation-induction (case vs. control: 5.0 vs. 3.8, P < 0.01). When data were dichotomized with the median values in the controls, a significantly increased risk for EC was observed for high baseline tail moment [odds ratio (OR) = 5.7, 95% confidence interval (CI) = 2.9-11.4], high BPDE-induced tail moment (OR = 5.8, 95% CI = 2.9-11.8), and high gamma-radiation-induced tail moment (OR = 4.6, 95% CI = 2.4-8.8). Further, the association between DNA damage and EC was stronger in never smokers than in ever smokers. Compared with subjects not sensitive to both mutagens, individuals sensitive to only one mutagen showed a 3.4-fold risk for EC and those sensitive to both mutagens showed an 8.7-fold risk for EC. Thus, we conclude that susceptibility to DNA damage as assessed by comet assay might help identify individuals with high EC risk.