Polymorphisms in the CASP8 gene and the risk of epithelial ovarian cancer
Polymorphisms in the CASP8 gene and the risk of epithelial ovarian cancer
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DOI：
10.1016/j.ygyno.2011.05.031
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发表时间：
2011-09-01
影响因子：
4.7
通讯作者：
Wang, Detang
中科院分区：
文献类型：
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作者：
Ma, Xiangdong;Zhang, Jianfang;Wang, Detang
目标。CASE基因在细胞凋亡途径中起着中心作用，因此是一个看似合理的癌症易感基因。然而，CASE基因在上皮性卵巢癌发生中的确切作用尚不清楚。因此，我们分析了单核苷酸多态(SNPs)与单倍型的相关性，以及中国人群上皮性卵巢癌(FOC)的风险和临床特征。使用MassARRAY系统鉴定了8个标签SNPs，在100名无关的健康女性中对CASP8基因周围和内部的37个遗传多态进行了基因分型。然后。对居住年龄和种族匹配的218例FOC患者和285例对照进行了这8个标签SNP的病例对照研究。CASP8rs3834129Ins>；del(优势比(OR)(del/del)=0.129，95%可信区间(95%CI)：0.038~0.439；OR(Ins/del)=0.769，95%CI，0.534~1.108)、rs3769827T>；C(OR(c/c)=0.187，95%CI：0.070~0.500；or(T/C)=0.729，95%CI：0.505~1.052)显著降低卵巢癌的发生风险。Rs6704688 C&gT；T(OR(T/T)-=0.344，95%Cl，0.168-0.707：or(C/T)=0.802，95%Cl.0.552-1.166)和这3个SNP的del-C-T单倍型(OR=0.615，95%CI：0.453-0.8363)。此外，rs3834129Ins/del/del/del和rs3769827T/C+C/C基因型显著晚发(P<；0.0001)。CASE8基因的遗传变异可预防卵巢癌的发生，并延迟卵巢癌的发病年龄。此外，这些保护作用可能是由于启动子中的-652 6N Clel变异体导致caspase-8表达障碍所致。(C)2011 Elsevier Inc.保留所有权利。
Objective. The CASES gene plays a central role in the apoptotic pathway and is therefore a plausible cancer susceptibility gene. However, the precise role of the CASES gene in epithelial ovarian cancer carcinogenesis is unclear. Therefore, we analyzed the correlation between single nucleotide polymorphisms (SNPs) and haplotypes in CASES and the risk and clinical characteristics of epithelial ovarian cancer (FOC) 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 FOC 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% Cl): 0.038-0.439; OR(ins/del) = 0.769, 95% Cl, 0.534-1.108), rs3769827 T > C (OR(c/c) = 0.187, 95% Cl: 0.070-0.500: OR(T/C)= 0.729, 95% Cl: 0.505-1.052). rs6704688 C > T (OR(T/T)-= 0.344,95% Cl, 0.168-0.707: OR(C/T)= 0.802,95% Cl. 0.552-1.166) and with the del-C-T haplotype of these 3 SNPs (OR = 0.615, 95% Cl: 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 CASE8 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 clel variant in the promoter. (C) 2011 Elsevier Inc. All rights reserved.