Annals of Surgical Oncology

, Volume 16, Issue 7, pp 2028–2034

Caspase 9 and Caspase 8 Gene Polymorphisms and Susceptibility to Bladder Cancer in North Indian Population

  • Ruchika Gangwar
  • Anil Mandhani
  • Rama Devi Mittal
Urologic Oncology

DOI: 10.1245/s10434-009-0488-3

Cite this article as:
Gangwar, R., Mandhani, A. & Mittal, R.D. Ann Surg Oncol (2009) 16: 2028. doi:10.1245/s10434-009-0488-3

Abstract

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) (TaG2-3, T1G1-3) 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).

Conclusion

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.

Copyright information

© Society of Surgical Oncology 2009

Authors and Affiliations

  • Ruchika Gangwar
    • 1
  • Anil Mandhani
    • 1
  • Rama Devi Mittal
    • 1
  1. 1.Department of Urology and Renal TransplantationSanjay Gandhi Post Graduate Institute of Medical SciencesLucknowIndia

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