A six-nucleotide insertion-deletion polymorphism in the CASP8 promoter associated with risk and progression of bladder cancer

Clin Cancer Res. 2009 Apr 1;15(7):2567-72. doi: 10.1158/1078-0432.CCR-08-2829. Epub 2009 Mar 10.

Abstract

Purpose: Caspase-8 (CASP8) is a key regulator of apoptosis or programmed cell death, an essential defense mechanism against hyperproliferation and malignancy. We hypothesized that the variants in the CASP8 gene are associated with risk of bladder cancer.

Experimental design: In a hospital-based case-control study of 365 case patients with newly diagnosed bladder transitional cell carcinoma and 368 cancer-free controls frequency-matched by age and sex, we genotyped the functional -652 6N ins/del polymorphism (rs3834129) in the promoter of CASP8 and assessed its associations with risk of bladder cancer and interaction with tobacco smoking.

Results: A significant decreased risk of bladder cancer was found for the CASP8 -652 6N ins/del (adjusted odds ratio, 0.72; 95% confidence interval, 0.53-0.99) and del/del (odds ratio, 0.37; 95% confidence interval, 0.18-0.77) genotypes. Furthermore, a significant additive interaction between CASP8 polymorphism and tobacco smoking on bladder cancer risk was observed.

Conclusions: These results suggested that the CASP8 -652 6N ins/del polymorphism is involved in etiology of bladder cancer and thus may be a marker for genetic susceptibility to bladder cancer in Chinese populations. Larger studies are warranted to validate our findings.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Asian People / genetics
  • Case-Control Studies
  • Caspase 8 / genetics*
  • China
  • Disease Progression
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • INDEL Mutation*
  • Male
  • Middle Aged
  • Polymorphism, Genetic
  • Promoter Regions, Genetic
  • Smoking
  • Urinary Bladder Neoplasms / ethnology
  • Urinary Bladder Neoplasms / genetics*

Substances

  • CASP8 protein, human
  • Caspase 8