Caspase 9 and caspase 8 gene polymorphisms and susceptibility to bladder cancer in north Indian population.
BACKGROUND
Dysregulation of apoptosis plays a crucial role in carcinogenesis. Our aim was to investigate the association of Caspase 9 and Caspase 8 gene polymorphism with bladder cancer (BC) susceptibility.


METHODS
We undertook a case-control study of 212 (BC) cases and 250 controls to investigate the association between Caspase 9-1263A > G, Caspase 9-293del, and Caspase 8-6 N ins/del polymorphism and BC susceptibility by polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) method, and further to study the influence on recurrence in patients after Bacillus Calmette-Guerin (BCG) immunotherapy.


RESULTS
Overall, no statistically significant association was observed in Caspase 9-293del and Caspase 8. Nevertheless, Caspase 9-1263GG genotype was at reduced risk of BC [p = 0.010; odds ratio (OR) = 0.487]. Caspase 9-1263AG genotype was also observed to be significantly associated with reduced risk with high-risk non-muscle-invasive bladder cancer (NMIBC) (TaG(2-3), T1G(1-3)) and invasive tumors (T2 +) of BC (P = 0.042, OR = 0.39 and P = 0.013, OR = 0.028 respectively). Caspase 9-293del, heterozygous (-/+) genotype, too, demonstrated protective effect in high-risk NMIBC (P = 0.017; OR = 0.205). Haplotype analysis revealed variant genotypes Caspase 9AG + GG/Caspase 8 DI + II to be at reduced risk of BC (= 0P.014, OR = 0.47). The GG genotype of Caspase 9-1263 was associated with reduced risk for recurrence in BCG-treated patients [hazard ratio (HR) = 0.217, P = 0.005], thus showing increased recurrence-free survival (log-rank P = 0.024).


CONCLUSIONS
Polymorphism in Caspase 9-1263 was observed to play a protective role in susceptibility to BC risk. Caspase 9 gene variants were also associated with reduced risk of NMBIC stages. The variant G allele at Caspase 9-1263 may be responsible for increased recurrence-free survival in BCG-treated patients.
Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
Ruchika
R
Gangwar
Anil
A
Mandhani
Rama Devi
RD
Mittal
D000368:Aged; D016022:Case-Control Studies; D053181:Caspase 8 / Q000235:genetics*; D053453:Caspase 9 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007167:Immunotherapy; D007194:India; D008297:Male; D008875:Middle Aged; D009163:Mycobacterium bovis; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D011110:Polymorphism, Genetic; D016019:Survival Analysis; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000628:therapy
C505530:CASP8 protein, human; D053181:Caspase 8; D053453:Caspase 9