OBJECTIVE: The CASP8 gene plays a central role in the apoptotic pathway and is therefore a plausible cancer susceptibility gene. However, the precise role of the CASP8 gene in epithelial ovarian cancer carcinogenesis is unclear. Therefore, we analyzed the correlation between single nucleotide polymorphisms (SNPs) and haplotypes in CASP8 and the risk and clinical characteristics of epithelial ovarian cancer (EOC) in the Chinese population. SUBJECTS AND METHODS: Eight tag SNPs were identified using the MassARRAY system to genotype 37 genetic polymorphisms around and in the CASP8 gene in 100 unrelated, healthy females. Then, a case-control study of 218 EOC patients and 285 controls who were matched on residence, age and race was conducted using these 8 tag SNPs. RESULTS: The risk of developing EOC was significantly decreased in association with CASP8 rs3834129 ins>del (odds ratio (OR)(del/del)=0.129, 95% confidence interval (95% CI): 0.038-0.439; OR(ins/del)=0.769, 95% CI, 0.534-1.108), rs3769827 T>C (OR(C/C)=0.187, 95% CI: 0.070-0.500; OR(T/C)=0.729, 95% CI: 0.505-1.052), rs6704688 C>T (OR(T/T)=0.344, 95% CI, 0.168-0.707; OR(C/T)=0.802, 95% CI, 0.552-1.166), and with the del-C-T haplotype of these 3 SNPs (OR=0.615, 95% CI: 0.453-0.8363). Moreover, a notably later onset was significantly associated with the rs3834129 ins/del+del/del and the rs3769827 T/C+C/C genotypes (p<0.0001). CONCLUSIONS: Genetic variants of the CASP8 gene protect against EOC carcinogenesis and delay the age of EOC onset. Furthermore, these protective effects may be due to the dysfunctional expression of caspase-8 caused by the -652 6N del variant in the promoter.
OBJECTIVE: The CASP8 gene plays a central role in the apoptotic pathway and is therefore a plausible cancer susceptibility gene. However, the precise role of the CASP8 gene in epithelial ovarian cancer carcinogenesis is unclear. Therefore, we analyzed the correlation between single nucleotide polymorphisms (SNPs) and haplotypes in CASP8 and the risk and clinical characteristics of epithelial ovarian cancer (EOC) in the Chinese population. SUBJECTS AND METHODS: Eight tag SNPs were identified using the MassARRAY system to genotype 37 genetic polymorphisms around and in the CASP8 gene in 100 unrelated, healthy females. Then, a case-control study of 218 EOC patients and 285 controls who were matched on residence, age and race was conducted using these 8 tag SNPs. RESULTS: The risk of developing EOC was significantly decreased in association with CASP8rs3834129 ins>del (odds ratio (OR)(del/del)=0.129, 95% confidence interval (95% CI): 0.038-0.439; OR(ins/del)=0.769, 95% CI, 0.534-1.108), rs3769827 T>C (OR(C/C)=0.187, 95% CI: 0.070-0.500; OR(T/C)=0.729, 95% CI: 0.505-1.052), rs6704688 C>T (OR(T/T)=0.344, 95% CI, 0.168-0.707; OR(C/T)=0.802, 95% CI, 0.552-1.166), and with the del-C-T haplotype of these 3 SNPs (OR=0.615, 95% CI: 0.453-0.8363). Moreover, a notably later onset was significantly associated with the rs3834129 ins/del+del/del and the rs3769827 T/C+C/C genotypes (p<0.0001). CONCLUSIONS: Genetic variants of the CASP8 gene protect against EOC carcinogenesis and delay the age of EOC onset. Furthermore, these protective effects may be due to the dysfunctional expression of caspase-8 caused by the -652 6N del variant in the promoter.
Authors: Bridget Charbonneau; Ellen L Goode; Kimberly R Kalli; Keith L Knutson; Melissa S Derycke Journal: Crit Rev Immunol Date: 2013 Impact factor: 2.214
Authors: Cunzhong Yuan; Xiaoyan Liu; Xiaolin Liu; Ning Yang; Zhenping Liu; Shi Yan; Keng Shen; Beihua Kong Journal: PLoS One Date: 2015-09-30 Impact factor: 3.240
Authors: J D Kuhlmann; A Bankfalvi; K W Schmid; R Callies; R Kimmig; P Wimberger; W Siffert; H S Bachmann Journal: BMC Cancer Date: 2016-08-09 Impact factor: 4.430