title: Polymorphisms in the caspase-8 gene and the risk of lung cancer.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Konyang University College of Medicine, Naedong 26, Nonsan, 320-711, Korea.
authors.forename: Ji-Woong
authors.initials: JW
authors.lastname: Son
authors.forename: Hyo-Kyung
authors.initials: HK
authors.lastname: Kang
authors.forename: Myung Hwa
authors.initials: MH
authors.lastname: Chae
authors.forename: Jin Eun
authors.initials: JE
authors.lastname: Choi
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Park
authors.forename: Won Kee
authors.initials: WK
authors.lastname: Lee
authors.forename: Chang Ho
authors.initials: CH
authors.lastname: Kim
authors.forename: Dong Sun
authors.initials: DS
authors.lastname: Kim
authors.forename: Sin
authors.initials: S
authors.lastname: Kam
authors.forename: Young Mo
authors.initials: YM
authors.lastname: Kang
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Park
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D053181:Caspase 8; D020169:Caspases / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects
chemical_list: C505530:CASP8 protein, human; D053181:Caspase 8; D020169:Caspases