Genetic polymorphism of glutathione-s-transferase [GST-M1 and GST-T1] in Egyptian schistosomiasis -associated bladder cancer

ABSTRACT

Bladder cancer is a common neoplasm around the world. In Egypt, the majority of bladder cancer is associated with Schistosoma haematobium [S. haematobium]. Glutathione-s-transferase [GST] represents an important family of metabolizing enzymes that catalyzes the conjugation of large variety of endogenous and exogenous compounds including carcinogens and anti cancer drugs and their metabolites with reduced glutathione. Individuals with very low levels of GSTs are at increased risk for the development of carcinoma and inflammatory diseases. The potential role of GST gene polymorphism on bladder cancer susceptibility is less certain. So, the aim of this work was to study GST-M1 and GST-T1 genes polymorphism in Egyptian patients with S. haematobium to clarify its role on bladder cancer susceptibility in those patients. This was carried out on three groups, 15 Egyptian patients with S. haematobium with bladder cancer, 15 Egyptian patients with S. haematobium without bladder cancer and 10 normal individual as a control group. All individuals were subjected to measurement of serum level of GST using ELISA technique and genotyping for GST-M1 and GST-T1 using PCR technique. The results proved that GST serum level in Schistosoma patients without bladder cancer was decreased but not statistically significant if compared to control group, in contrast it was significantly deceased in Schistosoma patients with bladder cancer if compared to the other groups. PCR results for GST-M1 and GST-T1 genotyping had shown 4 categories, in control group [M1+ve/T1+ve [80%], M1+ve/T1-ve[10%], M1-ve/T1+ve[10%], M1-ve/T1/-ve[0%]], in Schistosoma without bladder cancer [M1+ve/T1+ve[66.7%], M1+ve /T1-ve[13.3%], M1-ve/T1+ve[13.3%], M1 -ve/T1-ve[6.7%]], while in Schistosoma patients with bladder cancer [M1+ve/T1+ve[13.3%], M1+ve/T1-ve[13.3%], M1-ve/T1+ve[20%] and M1-ve/T1-ve [53.3%]]. It was demonstrated a significant decrease in enzyme levels in patients with homozygous deletions of both GST-M1 and GST-T1 genes [GST-M1-ve/T1-ve] if compared to the other three categories of genotyping. Moreover, there was a significant increased risk for development of bladder cancer in patients with combined gene deletion [OR=40] which represented mainly in Schistosoma patients with bladder cancer [53.3% were M1-ve/T1-ve]. Bladder cancer is a common multifactorial disease, and genetic polymorphism especially in GST-M1 and GST-T1 could play an important role as a risk factors in development of urinary bladder cancer among Egyptian with Schistosoma haematobium. So, it could be used for early prediction of risk group in order to help them by follow up for early diagnosis or by cancer chemoprotection