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Genetic Polymorphism of Glutathione-S-Transferase (GST-M1 and
GST-T1) In Egyptian Schistosomiasis -Associated Bladder Cancer
Amal H. Abd El Hameed, Osama E. Negm1, Hala E. Hamouda2,
Osama M. El Gamal3, kholoud A. El Nouby4 &
Ghada M. Ismail5
Departments of Clinical Pathology, Tropical Medicine1,
Medical Biochemistry2, Urology3, Parasitology4
and Physiology5 -Tanta University, Egypt
Tanta Med. Sc. J 2007; 2(3):87-97
Article type: Original article
Background/Aim: 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. Patients & Methods: 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.
Results: 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). Conclusion: 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.
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