Significant association of the EXO1 rs851797 polymorphism with clinical outcome of ovarian cancer.
Significant association of the EXO1 rs851797 polymorphism with clinical outcome of ovarian cancer.
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EXO1 rs851797 多态性与卵巢癌临床结果的显着相关性
DOI：
10.2147/ott.s141668
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发表时间：
2017
影响因子：
4
通讯作者：
Zang R
中科院分区：
文献类型：
--
作者：
Shi T;Jiang R;Wang P;Xu Y;Yin S;Cheng X;Zang R
背景核酸外切酶1（EXO1）是DNA错配修复途径基因之一，在维持基因组稳定性和影响肿瘤进展方面发挥着作用。我们假设 EXO1 的遗传变异可以预测上皮性卵巢癌 (EOC) 的临床结果。方法 在这项对 1,030 名连续 EOC 患者进行的队列研究中，我们通过 Taqman 检测对 EXO1 中的四个潜在功能多态性进行了基因分型，并评估了它们与患者生存的关联。结果使用多变量Cox比例风险回归模型，我们发现rs851797AG/GG基因型与复发和癌症死亡显着相关（HR分别为1.30和1.38，95% CI =1.11-1.52和1.02-1.88）。 Kaplan-Meier 生存估计显示，与 rs851797AA 基因型携带者相比，携带 rs851797AG/GG 基因型的患者无进展生存期和总生存期较差（对数秩检验，P 分别为 0.002 和 0.025）。此外，绝经期年龄较大、肿瘤处于晚期或接受不完全细胞减灭术的患者更有可能复发和死亡。结论 EXO1 rs851797 多态性可以预测 EOC 患者的临床结局。此外，绝经年龄、FIGO分期和完全细胞减灭术可能是卵巢癌的独立预后因素。有必要通过功能实验进行大型研究来验证这些发现。
Background Exonuclease 1 (EXO1), one of DNA mismatch repair pathway genes, functions in maintaining genomic stability and affects tumor progression. We hypothesized that genetic variations in EXO1 may predict clinical outcomes in epithelial ovarian cancer (EOC). Methods In this cohort study with 1,030 consecutive EOC patients, we genotyped four potentially functional polymorphisms in EXO1 by the Taqman assay and evaluated their associations with patients’ survival. Results Using multivariate Cox proportional hazards regression models, we found that rs851797AG/GG genotypes were significantly associated with recurrence and cancer death (HR =1.30 and 1.38, 95% CI =1.11–1.52 and 1.02–1.88, respectively). Kaplan–Meier survival estimates showed that patients who carried rs851797AG/GG genotypes had poorer progression-free survival and poorer overall survival, compared with rs851797AA genotype carriers (log-rank test, P=0.002 and 0.025, respectively). Moreover, patients with older age at menophania, advanced stage tumor, or being received incomplete cytoreduction were more likely to be recurrent and dead. Conclusion EXO1 rs851797 polymorphism can predict the clinical outcomes in EOC patients. In addition, age at menophania, FIGO stage, and complete cytoreduction might be independently prognostic factors of ovarian cancer. Large studies with functional experiments are warranted to validate these findings.