The prognostic value of basal DNA damage level in peripheral blood lymphocytes of patients affected by bladder cancer.

BACKGROUND

Bladder cancer (BC) is one of the most aggressive malignancies of the urinary tract, with the highest lifetime treatment costs per patient of all cancers, due to the high rate of recurrences requiring continuous surveillance. An early diagnosis is essential to improve survival of patients with BC. Noninvasive and sensitive molecular biomarkers are needed to improve current strategies for the detection and monitoring of BC. Previous studies suggested that elevated DNA damage levels and suboptimal nucleotide excision DNA repair (NER) may be associated with BC.

METHODS

In the present study, we investigated basal DNA damage and DNA repair capacity in peripheral blood mononuclear cells (PBMCs) from 146 newly diagnosed patients with BC and 155 controls using a modified comet assay able to evaluate NER activity after challenging cells by benzo(a)pyrene diolepoxide (BPDE).

RESULTS

We found an association between DNA damage levels in PBMCs of BC cases and patients' outcomes. Basal DNA damage at diagnosis was significantly increasing with tumor grades (trend test, P = 0.02) and risk classes (trend test, P = 0.02). The overall survival analysis showed that DNA damage in patients at BC diagnosis was significantly higher in subjects with a shorter survival time (hazard ratio = 3.7; 95% CI: 1.3-10.6; P = 0.02).

CONCLUSIONS

Based on these data, we suggest that DNA damage levels measured in PBMCs of patients with BC may potentially represent a prognostic marker associated with poor survival; further validation is needed to better stratify patients with BC for clinical trials.