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GSTM1 and GSTT1 genes are potential risk modifiers for bladder cancer
S Z Abdel-Rahman1, W A Anwar, W E Abdel-Aal
1Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston 77555-1110, USA.
Cancer Detection and Prevention
|April 17, 1998
Summary
Null genotypes for glutathione S-transferase genes GSTM1 and GSTT1 increase bladder cancer risk. These genetic variations, especially combined, heighten susceptibility to squamous cell carcinoma and may influence tumor outcomes, suggesting a public health approach for early detection.
Area of Science:
- Genetics
- Oncology
- Environmental Health
Background:
- Glutathione S-transferase (GST) enzymes play a crucial role in detoxifying environmental carcinogens.
- Polymorphisms in GST genes, such as GSTM1 and GSTT1, can impair detoxification capacity, potentially increasing susceptibility to cancer.
- Bladder cancer is a significant health concern, with environmental factors and genetic predispositions contributing to its development.
Purpose of the Study:
- To investigate the association between genetic polymorphisms in glutathione S-transferase genes (GSTM1 and GSTT1) and the risk of developing bladder cancer.
- To explore the role of these gene polymorphisms in the clinicopathological outcome of bladder cancer.
- To assess the combined effect of GSTM1 and GSTT1 null genotypes on bladder cancer risk and subtype susceptibility.
Main Methods:
- A case-control study was conducted involving 37 Egyptian bladder cancer patients and 34 matched controls.
- Genotyping for GSTM1 and GSTT1 polymorphisms was performed using established molecular techniques.
- Clinicopathological data, including tumor type (transitional cell carcinoma and squamous cell carcinoma) and schistosoma infection status, were collected and analyzed.
Main Results:
- The GSTM1 null genotype was associated with an increased relative risk of bladder cancer (OR = 2.99), particularly in squamous cell carcinoma (SCC) (OR = 5.70).
- The GSTT1 null genotype also showed a significant individual association with increased bladder cancer risk (OR = 4.93).
- Individuals with null genotypes for both GSTM1 and GSTT1 exhibited a substantially higher risk (OR = 9.92) and a greater susceptibility to SCC compared to transitional cell carcinoma (TCC).
Conclusions:
- Null genotypes for GSTM1 and GSTT1 are significant host risk factors for bladder cancer, both individually and in combination.
- The GSTM1 null genotype may influence the clinicopathological outcome of bladder tumors.
- Identifying individuals with these prevalent null genotypes could facilitate early detection and prevention strategies for environmentally induced cancers.