Molecular Oncology GRP & Virology CI, Portuguese Institute of Oncology, Rua Dr. Ant. Bernardino Almeida, Porto, Portugal.
Gene. 2012 Aug 10;504(2):279-83. doi: 10.1016/j.gene.2012.05.037. Epub 2012 May 24.
Cervical cancer is one of the most common cancers diagnosed in women worldwide. Mammalian cells are constantly exposed to a wide variety of genotoxic agents from both endogenous and exogenous sources. The RAD51 protein is required for meiotic and mitotic recombination and plays a central role in homology-dependent recombinational repair of double-strand breaks (DSBs). Given the functional relevance of the DNA repair system on carcinogenesis, potential associations between genetic polymorphisms of DNA repair genes, cancer risk and response to therapy have been intensively evaluated. This is the first study evaluating the role of the RAD51 G172T genetic variants in cancer prognosis and clinical outcome of cervical cancer patients.
We analyzed RAD51 G172T polymorphism genotypes in cervical cancer patients who underwent a platinum-based chemotherapy in combination with radiotherapy. Genotyping was performed by Taqman™ Allelic Discrimination methodology.
Concerning the overall survival rates found using Kaplan-Meier method and Log Rank Test, we observed that the mean survival rates were statistically different according to the patients RAD51 genotypes. The group of patients carrying the T allele present a higher mean survival rate than the other patients (102.3months vs. 86.4months, P=0.020). Using the Cox regression analysis, we found an increased overall survival time for T-carrier patients, when compared with GG genotype, with tumor stage, age and presence of lymph nodes as covariates [hazard ratio (HR), 0.373; 95% CI, 0.181-0.770; P=0.008]. Among patients (n=193), RAD51 genotype frequency distributions were not under the influence of clinicopathologic characteristics, namely, treatment response (P=0.508), recurrence (P=0.150) and tumor stage (P=0.250).
This is the first study evaluating the role of the RAD51 G172T genetic variants in cancer prognosis and clinical outcome of cervical cancer patients. Our results indicate an influence of the RAD51 genetic variants in overall survival of cervical cancer. Thereby, RAD51 G172T genotypes may provide additional prognostic information in cervical cancer patients who underwent cisplatin-based chemotherapy in combination with radiotherapy.
宫颈癌是全球女性最常见的癌症之一。哺乳动物细胞不断受到内源性和外源性多种遗传毒性物质的影响。RAD51 蛋白是减数分裂和有丝分裂重组所必需的，在同源依赖性双链断裂 (DSB) 的重组修复中发挥核心作用。鉴于 DNA 修复系统在致癌作用中的功能相关性，人们已经深入评估了 DNA 修复基因的遗传多态性与癌症风险和治疗反应之间的潜在关联。这是第一项评估 RAD51 G172T 遗传变异在宫颈癌患者癌症预后和临床结局中的作用的研究。
我们分析了接受铂类化疗联合放疗的宫颈癌患者的 RAD51 G172T 多态性基因型。采用 Taqman™ 等位基因区分法进行基因分型。
根据 Kaplan-Meier 方法和 Log Rank 检验的总生存率，我们观察到根据患者 RAD51 基因型，平均生存率存在统计学差异。携带 T 等位基因的患者组的平均生存率明显高于其他患者（102.3 个月对 86.4 个月，P=0.020）。使用 Cox 回归分析，我们发现与 GG 基因型相比，T 等位基因携带者的总生存时间增加，且肿瘤分期、年龄和淋巴结存在为协变量[风险比（HR），0.373；95%可信区间，0.181-0.770；P=0.008]。在 193 名患者中，RAD51 基因型频率分布不受临床病理特征的影响，即治疗反应（P=0.508）、复发（P=0.150）和肿瘤分期（P=0.250）。
这是第一项评估 RAD51 G172T 遗传变异在宫颈癌患者癌症预后和临床结局中的作用的研究。我们的结果表明，RAD51 遗传变异影响宫颈癌的总生存率。因此，RAD51 G172T 基因型可能为接受顺铂为基础的化疗联合放疗的宫颈癌患者提供额外的预后信息。
