Department of Urology, Mannheim Medical Center, University of Heidelberg, Mannheim, Germany.
Mol Carcinog. 2012 Nov;51(11):907-15. doi: 10.1002/mc.20860. Epub 2011 Oct 4.
Smoking is the main risk factor for urothelial bladder cancer. In former smokers the risk decreases but does not reach the low level of never smokers. This indicates reversible and permanent smoking-derived genetic alterations. Transcriptional changes may point to mechanisms, how smoking promotes urothelial bladder cancer. To identify smoking-derived transcriptional changes we performed gene expression profiling in current, former, and never smokers, using tumor and tumor-free urothelium from patients with nonmuscle-invasive urothelial bladder cancer (NMIBC) or muscle-invasive urothelial bladder cancer (MIBC). Smoking turned out to influence gene expression much less than tumor stage (NMIBC or MIBC) and tumor transformation (tumor-free or tumor). Smoking seemed to influence gene expression in patients with MIBC more strongly compared to those with NMIBC. The least irreversible changes after smoking cessation were proposed in tumor-free urothelium from patients with NMIBC. Growth factors and oncogenes were up-regulated in tumor-free urothelium from smokers with MIBC but not from smokers with NMIBC. A panel of genes up-regulated in smokers have potential for early detection and distinction of MIBC from NMIBC using tumor-free tissue.
吸烟是膀胱癌的主要危险因素。在曾经吸烟者中，风险降低，但仍未降至从不吸烟者的低水平。这表明吸烟导致的遗传改变是可逆转和永久性的。转录变化可能指出吸烟促进膀胱癌的机制。为了鉴定吸烟引起的转录变化，我们使用非肌层浸润性膀胱癌（NMIBC）或肌层浸润性膀胱癌（MIBC）患者的肿瘤和肿瘤正常的尿路上皮组织，对当前吸烟者、曾经吸烟者和从不吸烟者进行了基因表达谱分析。结果表明，吸烟对基因表达的影响远小于肿瘤分期（NMIBC 或 MIBC）和肿瘤转化（肿瘤正常或肿瘤）。与 NMIBC 患者相比，吸烟似乎对 MIBC 患者的基因表达影响更大。与 MIBC 患者相比，NMIBC 患者在停止吸烟后，肿瘤正常尿路上皮的变化最小。在 MIBC 吸烟者的肿瘤正常尿路上皮中，生长因子和癌基因上调，但在 NMIBC 吸烟者中则没有。一组在吸烟者中上调的基因可能具有潜力，可通过肿瘤正常组织用于早期检测和区分 MIBC 与 NMIBC。
