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Fas 和 FasL 基因的遗传多态性与上皮性卵巢癌风险和临床结局相关。

Genetic polymorphisms in the Fas and FasL genes are associated with epithelial ovarian cancer risk and clinical outcomes.

机构信息

Department of Molecular Biology, Hebei Medical University, Fourth Hospital, Shijiazhuang, China.

出版信息

Gynecol Oncol. 2013 Mar;128(3):584-9. doi: 10.1016/j.ygyno.2012.12.002. Epub 2012 Dec 9.

Abstract

AIM

In this study, we evaluated whether functional polymorphisms within the Fas and FasL genes were associated with the risk of developing epithelial ovarian cancer (EOC) and survival of patients with EOC.

METHODS

A case-control study was performed in 342 EOC patients and 344 control women. The genotypes of three promoter region polymorphisms (Fas -1377G/A, -670A/G and FasL -844T/C) were determined using ligase detection reaction-polymerase chain reaction (LDR-PCR). The clinical outcomes in 202 EOC patients were compared across genotypes.

RESULTS

The genotype frequencies of the FasL -844 T/C polymorphism were significantly different between the case and control groups (P=0.034). Compared to the T/T and T/C genotypes, the C/C genotype significantly increased the risk of developing EOC (OR=1.46, 95% CI=1.08-1.99). The survival analysis showed that the Fas -1377G/A and -670A/G polymorphisms were related to prognosis in EOC patients. Compared with patients with the G/G genotype of the -1377G/A polymorphism, patients carrying the A allele had a shorter PFS and OS, as determined by univariate and multivariate analysis (HR=1.81, 95% CI=1.26-2.62 and HR=1.86, 95% CI=1.15-3.00, respectively). Similarly, Kaplan-Meier and Cox proportional hazard model analyses indicated that patients carrying the G allele of Fas -670A/G polymorphisms had shorter PFS and OS than those carrying the AA genotype (HR=1.67, 95% CI=1.15-2.42 and HR=1.80, 95% CI=1.10-2.94, respectively).

CONCLUSIONS

Functional polymorphisms in the Fas and FasL genes may be involved in epithelial ovarian cancer development and progression in northern Chinese women.

摘要

目的

本研究旨在评估 Fas 和 FasL 基因内的功能多态性是否与上皮性卵巢癌(EOC)的发病风险和 EOC 患者的生存相关。

方法

在 342 例 EOC 患者和 344 例对照女性中进行病例对照研究。使用连接酶检测反应-聚合酶链反应(LDR-PCR)确定三个启动子区域多态性(Fas-1377G/A、-670A/G 和 FasL-844T/C)的基因型。比较 202 例 EOC 患者的基因型与临床结局的关系。

结果

FasL-844T/C 多态性的基因型频率在病例组和对照组之间存在显著差异(P=0.034)。与 T/T 和 T/C 基因型相比,C/C 基因型显著增加了发生 EOC 的风险(OR=1.46,95%CI=1.08-1.99)。生存分析显示,Fas-1377G/A 和 -670A/G 多态性与 EOC 患者的预后相关。与 -1377G/A 多态性的 G/G 基因型患者相比,携带 A 等位基因的患者无进展生存期和总生存期更短,这一点在单因素和多因素分析中均得到了验证(HR=1.81,95%CI=1.26-2.62 和 HR=1.86,95%CI=1.15-3.00)。同样,Kaplan-Meier 和 Cox 比例风险模型分析表明,携带 Fas-670A/G 多态性的 G 等位基因的患者无进展生存期和总生存期较携带 AA 基因型的患者更短(HR=1.67,95%CI=1.15-2.42 和 HR=1.80,95%CI=1.10-2.94)。

结论

Fas 和 FasL 基因内的功能多态性可能与中国北方女性的上皮性卵巢癌发生和发展有关。

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