Polymorphisms in the caspase-8 gene and the risk of lung cancer

• Published in: Cancer genetics and cytogenetics 2006-09, Vol.169 (2), p.121-127
• Main Authors: Son, Ji-Woong, Kang, Hyo-Kyung, Chae, Myung Hwa, Choi, Jin Eun, Park, Jung Min, Lee, Won Kee, Kim, Chang Ho, Kim, Dong Sun, Kam, Sin, Kang, Young Mo, Park, Jae Yong
• Format: Article
• Language: English
• Subjects: Aged; Case-Control Studies; Caspase 8; Caspases - genetics; Female; Genetic Predisposition to Disease; Haplotypes; Humans; Lung Neoplasms - genetics; Male; Middle Aged; Polymorphism, Genetic; Risk Factors; Smoking - adverse effects
• ISSN: 0165-4608; 1873-4456
• DOI: 10.1016/j.cancergencyto.2006.04.001

Caspase-8 (CASP-8) is an initiator CASP in the cell death receptor–mediated apoptotic pathway, and plays an important role in the development of cancer. Polymorphisms and their haplotypes in the CASP-8 gene can result in alterations in CASP-8 expression and/or activity, thereby modulating the susceptibility to lung cancer. To test this hypothesis, we examined the association of -678_-673delAGTAAG (−678del) and IVS12-19G→A polymorphisms and their haplotypes with the risk of lung cancer in a Korean population. The CASP-8 genotypes were determined in 432 lung cancer patients and 432 healthy age- and gender-matched control subjects. The distributions of the CASP-8 −678del and IVS12-19G→A genotypes were not significantly different between the overall lung cancer cases and the controls. When the cases were categorized by tumor histology, however, the IVS12-19 AA genotype and the combined IVS12-19 GA + AA genotype were associated with a significantly decreased risk of small cell carcinoma (SmCC) compared with the IVS12-19 GG genotype [adjusted odds ratio (OR) = 0.14, 95% confidence interval (CI) = 0.03–0.64, P = 0.01; and adjusted OR = 0.56, 95% CI = 0.33–0.96, P = 0.03, respectively]. Consistent with the genotyping analyses, the −678del−/IVS12-19A haplotype containing 94% of the IVS12-19A allele in the study population was associated with a significantly decreased risk of SmCC compared with the −678del−/IVS12-19G (adjusted OR = 0.58, 95% CI = 0.36–0.93, P = 0.023, and Pc = 0.046). These findings suggest that the CASP-8 gene may contribute to an inherited predisposition to SmCC of the lung.