- 作者：Augusto Nogueira ; Raquel Catarino ; Ilda Faustino ; Cristina Nogueira-Silva ; Tiago Figueiredo ; Liliana Lombo ; In¨ºs Hil¨¢rio-Silva ; Deolinda Pereira ; Rui Medeiros
- 关键词：5-FU ; 5-fluorouracil ; RCT ; radiochemotherapy ; HPV ; Human papillomavirus ; DSB ; double-strand break(s) ; HR ; homologous recombination ; NHEJ ; non-homologous recombination ; kb ; kilobase ; UTR ; untranslated region(s) ; SNP ; single nucleotide polymorphism(s) ; MAF
- 刊名：Gene
- 出版年：2012
- 出版时间：10 August, 2012
- 年：2012
- 卷：504
- 期：2
- 页码：279-283
- 全文大小：235 K
Introduction
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.Material and methods
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.
Results and discussion
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 (102.3 months vs. 86.4 months, 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).
Conclusions
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.