膀胱癌为泌尿系统最常见的恶性肿瘤，环境因素如化工染料，吸烟，化学药物等（均为DNA损伤剂）是其明确的致病因素，因此正常的DNA损伤修复功能是预防突变和肿瘤发生的重要保护机制。我们前期的工作发现膀胱癌中存在XPA低表达的现象，并且这种表达差异与肿瘤染色体畸变关系密切。本研究基于文献报道和我们的原创性发现，提出膀胱癌中XPA低表达不仅直接影响核苷酸切除修复（NER）能力，而且可能在DNA双链断裂损伤（DSBs）修复途径中发挥潜在的信号功能，从而导致缺失或扩增等染色体畸变的发生率增加。高突变发生是原癌基因和抑癌基因易于突变的基础，也可能是膀胱肿瘤易感性的本质。本研究有助于我们更深入全面地理解膀胱肿瘤发生和高异质性的机制，同时为膀胱癌治疗提供新的靶标。

Bladder cancer is the most common malignant tumor of urinary system, environmental factors such as chemical dyes, smoking, chemical drugs (all of them are DNA damage agents ) are definit pathogenic factors, so the DNA damage repair function is an important protective mechanism to prevent mutation and tumorigenesis. Our previous work found low XPA expression in bladder cancer, and this phenotype is closely related to chromosomal aberrations . According to our original findings and some clues reported, we suppose that low expression of XPA in bladder cancer engages in the disfunction of not only the nucleotide excision repair ( NER ), but also DNA double strand break ( DSB ) repair, leading to higher incidence of chromosome aberration. High mutation frequency is the basis of mutaions of oncogenes and anti-oncogenes, and may be the essence of bladder cancer susceptibility. This research has important theoretical significance and application value. For it may help us to better understand the mechanisms of generation and high heterogeneity of bladder cancer, then provide a new treatment target for carcinoma of urinary bladder.