Document Detail


Role of the RAD51 G172T polymorphism in the clinical outcome of cervical cancer patients under concomitant chemoradiotherapy.
MedLine Citation:
PMID:  22634097     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 (102.3months 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).
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.
Authors:
Augusto Nogueira; Raquel Catarino; Ilda Faustino; Cristina Nogueira-Silva; Tiago Figueiredo; Liliana Lombo; Inês Hilário-Silva; Deolinda Pereira; Rui Medeiros
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-05-24
Journal Detail:
Title:  Gene     Volume:  504     ISSN:  1879-0038     ISO Abbreviation:  Gene     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-06-26     Completed Date:  2012-08-27     Revised Date:  2012-09-21    
Medline Journal Info:
Nlm Unique ID:  7706761     Medline TA:  Gene     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  279-83     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier B.V. All rights reserved.
Affiliation:
Molecular Oncology GRP & Virology CI, Portuguese Institute of Oncology, Rua Dr. Ant. Bernardino Almeida, Porto, Portugal.
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MeSH Terms
Descriptor/Qualifier:
Combined Modality Therapy
Female
Humans
Middle Aged
Polymorphism, Genetic*
Rad51 Recombinase / genetics*
Treatment Outcome
Uterine Cervical Neoplasms / drug therapy,  radiotherapy,  therapy*
Chemical
Reg. No./Substance:
EC 2.7.7.-/RAD51 protein, human; EC 2.7.7.-/Rad51 Recombinase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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