title: New insights into the influence of cigarette smoking on urothelial carcinogenesis: smoking-induced gene expression in tumor-free urothelium might discriminate muscle-invasive from nonmuscle-invasive urothelial bladder cancer.
abstract: 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.
authors: Department of Urology, Mannheim Medical Center, University of Heidelberg, Mannheim, Germany.
authors: Ute
authors: U
authors: Gabriel
authors: Li
authors: L
authors: Li
authors: Christian
authors: C
authors: Bolenz
authors: Annette
authors: A
authors: Steidler
authors: Bettina
authors: B
authors: Kränzlin
authors: Maria
authors: M
authors: Saile
authors: Norbert
authors: N
authors: Gretz
authors: Lutz
authors: L
authors: Trojan
authors: Maurice Stephan
authors: MS
authors: Michel
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D005786:Gene Expression Regulation; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D015398:Signal Transduction; D012907:Smoking / Q000009:adverse effects* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016540:Smoking Cessation; D001743:Urinary Bladder / Q000378:metabolism / Q000473:pathology*; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D019459:Urothelium / Q000378:metabolism / Q000473:pathology*