From the Guidelines
Transitional cell carcinoma (TCC), also known as urothelial carcinoma, is primarily caused by several risk factors, including tobacco smoking, occupational exposure to certain chemicals, chronic urinary tract infections and inflammation, genetic factors, and age. The causes of TCC can be broken down into several key areas:
- Tobacco smoking: The most significant risk factor, accounting for approximately 50-65% of cases in men and 20-30% in women, as the carcinogens in cigarette smoke are excreted in urine and directly damage the urothelial lining 1.
- Occupational exposure: Certain chemicals, particularly aromatic amines found in the dye, rubber, leather, paint, and printing industries, significantly increase the risk of developing TCC 1.
- Chronic urinary tract infections and inflammation: Conditions such as long-term catheter use or schistosomiasis (a parasitic infection) can lead to cellular changes that may progress to TCC 1.
- Genetic factors: Certain inherited genetic mutations increase susceptibility to TCC, highlighting the importance of genetic predisposition in the development of this disease 1.
- Age: TCC risk increases with advancing age, with most diagnoses occurring after age 65, emphasizing the need for vigilant screening in older adults 1. Other contributing factors include certain medications like cyclophosphamide (a chemotherapy drug), arsenic in drinking water, and prior pelvic radiation therapy, all of which can increase the risk of developing TCC. Understanding these risk factors is crucial for prevention strategies and early detection, especially for individuals with multiple risk factors who may benefit from more vigilant screening.
From the Research
Causes of Transitional Cell Carcinoma
The causes of transitional cell carcinoma (TCC) are multifactorial, involving both environmental and genetic factors. Some of the key causes include:
- Environmental exposures, such as tobacco smoke and occupational exposure to aromatic amines 2
- Family history, which confers a 2-fold increase in bladder cancer risk 2
- Genetic predisposition, with polymorphisms in genes involved in the metabolism of environmental toxins (e.g., NAT2) modifying individual susceptibility to bladder cancer 2
- Marijuana use, with a case report suggesting an association between heavy marijuana use and TCC 3
- Phenacetin abuse and smoking, which are established risk factors for TCC 4
- Chronic tissue damage, which may be a causative factor in the evolution of urothelial carcinomas rather than a direct mutagenic effect of phenacetin and tobacco-specific carcinogens 4
Genetic and Epigenetic Aspects
Genetic and epigenetic changes play a crucial role in the development of TCC. These changes include:
- p53 mutations, which are found in approximately 33% of renal pelvic carcinomas and are associated with poorer survival 4
- Genetic polymorphism in genes coding for carcinogen-metabolising enzymes (CYP1A1, NAT1, GSTT1, and GSTM1) 4
- Epigenetic changes, such as DNA methylation and histone modification, which can affect gene expression and contribute to the development of TCC 5
Molecular Biology
The molecular biology of TCC is complex and involves multiple genetic and epigenetic alterations. These alterations can affect various cellular pathways, including cell cycle regulation, apoptosis, and DNA repair. Understanding the molecular biology of TCC is essential for the development of effective therapies and prognostic markers 6, 5