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.
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).
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).
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.
Urologic oncology. 2018 Feb 06 [Epub ahead of print]
Alessandra Allione, Barbara Pardini, Clara Viberti, Marco Oderda, Marco Allasia, Paolo Gontero, Paolo Vineis, Carlotta Sacerdote, Giuseppe Matullo
Genomic variation in human population and complex diseases Research Unit, Italian Institute for Genomic Medicine (IIGM), Turin, Italy; Department of Medical Sciences, University of Turin, Turin, Italy. Electronic address: ., Genomic variation in human population and complex diseases Research Unit, Italian Institute for Genomic Medicine (IIGM), Turin, Italy; Department of Medical Sciences, University of Turin, Turin, Italy., Department of Surgical Science, A.O. Città della Salute e della Scienza di Torino-Presidio Molinette, University of Turin, Turin, Italy., Genomic variation in human population and complex diseases Research Unit, Italian Institute for Genomic Medicine (IIGM), Turin, Italy; School of Public Health, Epidemiology & Biostatistics, MRC-HPA Centre for Environment and Health, Imperial College London, London, United Kingdom., Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), Turin, Italy.