title: The six-nucleotide deletion/insertion variant in the CASP8 promoter region is inversely associated with risk of squamous cell carcinoma of the head and neck.
abstract: Caspase 8 (CASP8) is an apoptosis-related cysteine peptidase involved in the death receptor pathway and likely in the mitochondrial pathway. A CASP8 promoter region six-nucleotide deletion/insertion (-652 6N ins/del) variant and a coding region D302H polymorphism are reportedly important in cancer development, but no reported study has assessed the associations of these genetic variations with risk of head and neck cancer. In a hospital-based study of non-Hispanic whites, we genotyped CASP8 -652 6N del and 302H variants in 1,023 patients with squamous cell carcinoma of the head and neck (SCCHN) and 1,052 cancer-free controls. Crude and adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression models. The CASP8 -652 6N del variant genotypes or haplotypes were inversely associated with SCCHN risk (adjusted OR, 0.70; 95% CI, 0.57-0.85 for the ins/del + del/del genotypes compared with the ins/ins genotype; adjusted OR, 0.73; 95% CI, 0.55-0.97 for the del-D haplotype compared with the ins-D haplotype). Furthermore, the number of the CASP8 -652 6N del (but not 302H) variant allele tended to correlate with increased levels of camptothecin-induced p53-mediated apoptosis in T lymphocytes from 170 cancer-free controls. We concluded that the CASP8 -652 6N del variant allele may contribute to the risk of developing SCCHN in non-Hispanic white populations. Further validation by population-based case-control studies and rigorous mechanistic studies is warranted.
authors.affiliation: Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston, 77030, USA.
authors.forename: Chunying
authors.initials: C
authors.lastname: Li
authors.forename: Jiachun
authors.initials: J
authors.lastname: Lu
authors.forename: Zhensheng
authors.initials: Z
authors.lastname: Liu
authors.forename: Li-E
authors.initials: LE
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.forename: Adel K
authors.initials: AK
authors.lastname: El-Naggar
authors.forename: Erich M
authors.initials: EM
authors.lastname: Sturgis
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
mesh_terms: D017209:Apoptosis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D053181:Caspase 8 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D009367:Neoplasm Staging; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012307:Risk Factors; D017384:Sequence Deletion; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: C505530:CASP8 protein, human; D053181:Caspase 8