Allione Alessandra, Pardini Barbara, Viberti Clara, Oderda Marco, Allasia Marco, Gontero Paolo, Vineis Paolo, Sacerdote Carlotta, Matullo Giuseppe
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.
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.
Urol Oncol. 2018 May;36(5):241.e15-241.e23. doi: 10.1016/j.urolonc.2018.01.006. Epub 2018 Feb 14.
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.
膀胱癌（BC）是泌尿系统中侵袭性最强的恶性肿瘤之一，由于复发率高，需要持续监测，其每位患者的终身治疗成本在所有癌症中最高。早期诊断对于提高膀胱癌患者的生存率至关重要。需要非侵入性且敏感的分子生物标志物来改进当前膀胱癌的检测和监测策略。先前的研究表明，DNA损伤水平升高和核苷酸切除DNA修复（NER）欠佳可能与膀胱癌有关。
在本研究中，我们使用一种改良的彗星试验，通过苯并(a)芘二环氧物（BPDE）刺激细胞后评估NER活性，调查了146例新诊断的膀胱癌患者和155名对照者外周血单核细胞（PBMC）中的基础DNA损伤和DNA修复能力。
我们发现膀胱癌患者PBMC中的DNA损伤水平与患者预后之间存在关联。诊断时的基础DNA损伤随肿瘤分级（趋势检验，P = 0.02）和风险类别（趋势检验，P = 0.02）显著增加。总体生存分析表明，膀胱癌诊断时患者的DNA损伤在生存时间较短的受试者中显著更高（风险比 = 3.7；95%可信区间：1.3 - 10.6；P = 0.02）。
基于这些数据，我们认为在膀胱癌患者PBMC中测量的DNA损伤水平可能潜在地代表一种与不良生存相关的预后标志物；需要进一步验证以更好地将膀胱癌患者分层用于临床试验。
