الفهرس 
TitleOnly 14 pages are availabe for public view
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Abstract
Bladder cancer is the 9th most commonly diagnosed cancer worldwide, which occur
more commonly in elderly patients with a strong male predominance. Well established risk
factors for BC include smoking, occupational exposures to aromatic amines and polycyclic
aromatic hydrocarbons and infections especially with Schistosoma haematobium.
Genetic predisposition play a critical role in determining the risk of BC. Many
genetic variations in different pathways have been documented in the carcinogenesis of BC
leading to alterations in gene regulation and gene expression. GSTs family related enzymes
that detoxify reactive chemical species such as polycyclic aromatic hydrocarbon and so
serve as protecting factors against cytotoxic and potentially carcinogenic chemicals. They
also have a key role in the response to therapeutic agents. Polymorphic deletion of GSTM1
and GSTT1 genes and the GSTO2 A424G polymorphism are associated with an increased
risk of bladder cancer.
The aim of the present study was to assess the role of GSTM1 and GSTT1
polymorphic deletions and GSTO2 genotypes as risk factors for developing BC in a sample
of Egyptian patients and to study their effect on the response to BCG immunotherapy in
NMIBC patients.
The present study included 68 BC patients from the Urology Department, Faculty of
Medicine, Alexandria University.The study also included 100 healthy volunteers as control
group.
All patients were subjected to:
1. History taking including personal and occupational data, history of smoking, medical
history, drug history and family history of bladder cancer or any other cancer.
2. Investigations including: urinary cytology, ultrasound abdomen and pelvis and CT
abdomen and pelvis.
3. Cystoscopic examination of the bladder followed by histopathological evaluation of
the biopsy.
4. Patients received intravesical instillations of BCG once a week for 6 consecutive
weeks.
5. Follow up cystoscopy after 3 and 6 months of BCG therapy.
6. Molecular genetic testing for GSTT1 and GSTM1 polymorphic deletions using
multiplex polymerase chain reaction method.
7. Molecular genetic testing for GSTO2 A424G using polymerase chain reaction
restriction fragment length polymorphism (PCR- RFLP).
The results of the current study were:
1. Age of patients ranged from 17-77 years with the mean ± standard deviation of 56.8
± 11.46 years.
2. Males represented (89.7%) while females represented (10.3%).
3. Forty seven patients (69.1%) were smokers, 5 patients (7.4%) were ex-smokers and
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16 patients (23.5%) were non-smokers. In the control group, 60 were smokers (60%),
40 were non-smokers (40%) and there was no any ex-smoker in this group. There
was a statistical significant difference between smokers and non-smokers among
patients and control (p=0.004).
4. Occupational risk factors were reported in 11 patients (16.2%) compared to control
(4%) while no occupational risk factors were found in 57 patients (83.8%) compared
with 96 control (96%). There was no statistical significant difference between among
patients and control regarding occupational risk factor (p= 0.768).
5. A positive family history for BC was reported in 5.9%.
6. By applying multiple logistic regression model, age and smokingare predictors for
BC risk (p= 0.006, 0.004 respectively)
7. The GSTM1 deletion (null) was observed in 28 patients (41.2%) compared with 33
control (33%) whereas the normal GSTM1 genotype was observed in 40 patients
(58.8%) compared with 67 in the control group (67%). There was a significant
statistical difference between distribution of GSTM1 genotypes among case and
control (p value=0.013).
8. The GSTT1 deletion (null) was observed in 39 patients (57.3%) compared with 51
control (51%) while the normal GSTT1 genotypes was observed in 29 patients
(42.7%) compared with 49 control (49%). There was a significant statistical
difference between distribution of GSTT1 genotypes among case and control (p value
= 0.001).
9. The A/A genotype of GSTO2 A424G polymorphism was observed in 40 patients
(58.8%) compared with 55control (55%) while the A/G genotype was found in 26
patients (38.8%) compared with 44 control (44%) while the G/G genotype was
shown in 2 patients (2.9%) compared with 1 control (1%). There was a significant
statistical difference between distribution of GSTO2 genotypes among cases and
control (p value = 0.01)
10. GSTM1/ GSTT1 null/null genotypes was observed in 27.9% in patients compared to
11% in the control group. There was a significant statisticaldifferencebetween both
GSTM1 and GSTT1 null genotypes and other genotypes with at least one normal
allele. (pvalue = 0.005)
11. After treatment with BCG immunotherapy, 23 patients (33.8%) were responders
while 45 patients (66.2%) were non-responders.
12. The GSTM1 deletion (null) allele was observed in 9 patients within the BCG
responders group (39.1%) compared with 19 patients within the non–responders
group (42.2%) whereas the normal GSTM1 genotype was found in 14 patients
(60.9%) in the responders group compared with 26 patients in the non–
respondersgroup (57.8%). There was no significant statistical difference between
distribution of GSTM1 genotypes among responders and non-responders to BCG (p
value=0.1).
13. The GSTT1 deletion (null) allele was observed in 13 patients within the BCG
responders group (56.6%) compared with 26 patients within the non–responders
group (57.8%) whereas the normal GSTT1 genotype was found in 10 patients
(43.4%) in the responders group compared with 19 patients in the non–responders
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group (42.2%). There was no significant statistical difference between distribution of
GSTT1 genotypes among responders and non-responders to BCG (p value=0.474).
14. The A/A genotype of GSTO2 A424G polymorphism was found in 13 patients within
the responders (56.6%) compared with 27 patients within non-responders (60%)
while the A/G genotype was found in 9 patients within the responders (39.1%)
compared with17 patients within the non-responders (37.8%) while the G/G
genotype was shown in one patient within the responders (4.3%) compared with one
patient within the non-responders (2.2%). There was no significant statistical
difference between distribution of GSTO2 genotypes among responders and nonresponders
to BCG (p value= 0.352).