Polymorphisms in the CASP8 gene and the risk of epithelial ovarian cancer |
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Authors: | Ma Xiangdong Zhang Jianfang Liu Shujuan Huang Yanhong Chen Biliang Wang Detang |
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Institution: | Department of Obstetrics and Gynecology, Xijing Hospital, Fourth Military Medical University, 17 Changle West Road, Xi'an, 710032, PR China |
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Abstract: | ObjectiveThe 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 methodsEight 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.ResultsThe 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; ORins/del = 0.769, 95% CI, 0.534-1.108), rs3769827 T > C (ORC/C = 0.187, 95% CI: 0.070-0.500; ORT/C = 0.729, 95% CI: 0.505-1.052), rs6704688 C > T (ORT/T = 0.344, 95% CI, 0.168-0.707; ORC/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).ConclusionsGenetic 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 6 N del variant in the promoter. |
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Keywords: | CASP8 Epithelial ovarian cancer Polymorphism Genetic association |
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