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Am. J. Biomed. Sci. 2010, 2(2), 121-128; doi: 10.5099/aj100200121
Received: 28 June 2009; | Revised: 16 August 2009; | Accepted: 15 December 2009
 

The CASPASE-8 Insertion/Deletion Polymorphism and Risk of Non-small Cell Lung Cancer
 

Shanbeh Zienolddiny1,*, Kine Martinsen1, Vidar Skaug1, Per Olav Ekstrøm2 and Aage Haugen1

1Department of Chemical and Biological Working Environment, Section of Toxicology, National Institute of Occupational Health, N-0033 Oslo, Norway.

2Department of Surgical Oncology, The Norwegian Radium Hospital, Montebello, Oslo, Norway.

*Corresponding author

Shan Zienolddiny

Department of Chemical and Biological Working Environment

Section of Toxicology

National Institute of Occupational Health

N-0033 Oslo, Norway

Tel.: +4723195100; fax +4723195203

E-mail: shan.zienolddiny@stami.no

 

Abstract

The cysteine-dependent aspartate-specific protease 8 (CASP8) is a key enzyme in the apoptosis and genetic polymorphisms in this gene have been reported to affect the gene expression and its enzymatic activity. A six-nucleotide insertion-deletion polymorphism (-652 6N ins/del, rs3834129) in the CASP8 promoter has been shown to be associated with susceptibility to multiple cancers in the Asian populations. Here we report results of genotyping the CASP8 ins/del polymorphism in non-small cell lung cancer (NSCLC) cases and controls from Norway, all of which are of Caucasian origin. The overall odds ratio for NSCLC was 1.40 (95% CI, 0.95-2.06). When subjects were grouped according to gender, males carrying del/del genotype had an increased odds ratio for developing NSCLC with an OR of 1.61 (95% CI, 1.02-2.53, P=0.039). Somatic mutations of the TP53 gene in tumors were also analyzed and the results showed no interaction between alterations in TP53 and the CASP8 polymorphism. These results contradict a protective effect of this polymorphism on lung cancer as it has been reported in the Asian populations. The results are discussed in relation to population and exposure specific effects of this polymorphism.

Keywords:  CASP8; lung cancer; NSCLC; polymorphism; TP53.

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