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


METHODS
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.
Wang
Meilin
M
Department of Molecular and Genetic Toxicology and Epidemiology and Biostatistics, Cancer Center of Nanjing Medical University, Nanjing, People's Republic of China.
Zhang
Zhizhong
Z
Tian
Yuanyuan
Y
Shao
Jianfeng
J
Zhang
Zhengdong
Z
D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D053181:Caspase 8 / Q000235:genetics*; D002681:China; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D054643:INDEL Mutation; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012907:Smoking; D001749:Urinary Bladder Neoplasms / Q000208:ethnology / Q000235:genetics*
C505530:CASP8 protein, human; D053181:Caspase 8