Department of Urology, Asklipieio General Hospital, Voula, Athens, Greece; Unit of Biomedical Applications, Institute of Biological Research and Biotechnology, National Hellenic Research Foundation, 48 Vas. Constantinou Ave, 116 35 Athens, Greece.
Toxicol Lett. 2010 Mar 15;193(2):131-7. doi: 10.1016/j.toxlet.2009.12.018. Epub 2010 Jan 4.
Cancer of the urinary bladder is the second most common malignancy of the genitourinary tract, currently accounting for up to 5% of all newly diagnosed tumours in the western world. Urinary bladder carcinogenesis seems to develop from the interaction of environmental exposure and genetic susceptibility. Smoking, specific industrial chemicals, dietary nitrates and arsenic represent the most important exogenous risk factors. Chromosomal abnormalities, silencing of certain genes by abnormal methylation of their promoter region, alterations in tumour suppressor genes and proto-oncogenes that induce uncontrolled cell proliferation and reduced apoptosis, are molecular mechanisms that have been reported in bladder carcinogenesis. In this article, we discuss the environmental risk factors of bladder cancer and we review the genetic and epigenetic alterations, including aberrant DNA methylation and deregulation of microRNAs expression. We also discuss the role of p53 and retinoblastoma suppressor genes in disease progression. Finally, we present recent reports on the use of molecular profiling to predict disease stage and grade and direct targeted therapy.
膀胱癌是泌尿生殖道第二大常见恶性肿瘤，目前在西方世界占所有新诊断肿瘤的 5%。膀胱癌的发生似乎是由环境暴露和遗传易感性的相互作用引起的。吸烟、特定的工业化学品、饮食中的硝酸盐和砷是最重要的外源性危险因素。染色体异常、特定基因因启动子区域异常甲基化而沉默、肿瘤抑制基因和原癌基因的改变，这些导致不受控制的细胞增殖和减少细胞凋亡的分子机制已在膀胱癌的发生中得到报道。在本文中，我们讨论了膀胱癌的环境危险因素，并回顾了遗传和表观遗传改变，包括异常的 DNA 甲基化和 microRNAs 表达的失调。我们还讨论了 p53 和视网膜母细胞瘤抑制基因在疾病进展中的作用。最后，我们介绍了最近关于利用分子谱分析预测疾病分期和分级并指导靶向治疗的报告。
