PURPOSE: Caspase-3 plays a central role in executing cell apoptosis and thus in carcinogenesis, but little is known about the role of CASP3 variants in susceptibility to SCCHN. EXPERIMENTAL DESIGN: Genotype and haplotypes of the first intron (rs4647601:G>T and rs4647602:C>A) and 5'-untranslated region (UTR; rs4647603:G>A) of CASP3 (NT_022792.17) were determined for 930 SCCHN patients and 993 cancer-free controls in a U.S. non-Hispanic white population. Odds ratio (OR) and 95% confidence interval (95% CI) were calculated in multivariate logistic regression analysis. RESULTS: We found that the CASP3 rs4647601:TT variant genotype was associated with an increased risk of SCCHN (adjusted OR, 1.32; 95% CI, 1.00-1.73) compared with the GG genotype. This risk was more evident in the subgroups of younger (< or =56 years) subjects, males, and never smokers with a significant trend for increased risk with increased number of variant T allele (P < 0.05 for all). However, these risks were not found for other two SNPs. Furthermore, individuals with two copies of haplotypes TCG or GCA were found to have a significant increased risk of SCCHN (OR, 1.31; 95% CI, 1.07-1.61) compared with the other haplotypes, and this risk was more evident in less advanced diseases (OR, 1.45; 95% CI, 1.11-1.89) than in the advanced diseases (OR, 1.22; 95% CI, 0.96-1.54). CONCLUSIONS: These results suggested that genetic variation in CASP3 may contribute to SCCHN risk. Larger studies are needed to confirm our findings.
PURPOSE:Caspase-3 plays a central role in executing cell apoptosis and thus in carcinogenesis, but little is known about the role of CASP3 variants in susceptibility to SCCHN. EXPERIMENTAL DESIGN: Genotype and haplotypes of the first intron (rs4647601:G>T and rs4647602:C>A) and 5'-untranslated region (UTR; rs4647603:G>A) of CASP3 (NT_022792.17) were determined for 930 SCCHN patients and 993 cancer-free controls in a U.S. non-Hispanic white population. Odds ratio (OR) and 95% confidence interval (95% CI) were calculated in multivariate logistic regression analysis. RESULTS: We found that the CASP3rs4647601:TT variant genotype was associated with an increased risk of SCCHN (adjusted OR, 1.32; 95% CI, 1.00-1.73) compared with the GG genotype. This risk was more evident in the subgroups of younger (< or =56 years) subjects, males, and never smokers with a significant trend for increased risk with increased number of variant T allele (P < 0.05 for all). However, these risks were not found for other two SNPs. Furthermore, individuals with two copies of haplotypes TCG or GCA were found to have a significant increased risk of SCCHN (OR, 1.31; 95% CI, 1.07-1.61) compared with the other haplotypes, and this risk was more evident in less advanced diseases (OR, 1.45; 95% CI, 1.11-1.89) than in the advanced diseases (OR, 1.22; 95% CI, 0.96-1.54). CONCLUSIONS: These results suggested that genetic variation in CASP3 may contribute to SCCHN risk. Larger studies are needed to confirm our findings.
Authors: H Shen; E M Sturgis; S G Khan; Y Qiao; T Shahlavi; S A Eicher; Y Xu; X Wang; S S Strom; M R Spitz; K H Kraemer; Q Wei Journal: Cancer Res Date: 2001-04-15 Impact factor: 12.701
Authors: F C Kischkel; D A Lawrence; A Tinel; H LeBlanc; A Virmani; P Schow; A Gazdar; J Blenis; D Arnott; A Ashkenazi Journal: J Biol Chem Date: 2001-10-02 Impact factor: 5.157
Authors: Saravana P Selvanathan; Garrett T Graham; Hayriye V Erkizan; Uta Dirksen; Thanemozhi G Natarajan; Aleksandra Dakic; Songtao Yu; Xuefeng Liu; Michelle T Paulsen; Mats E Ljungman; Cathy H Wu; Elizabeth R Lawlor; Aykut Üren; Jeffrey A Toretsky Journal: Proc Natl Acad Sci U S A Date: 2015-03-03 Impact factor: 11.205