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Previous issue date: 2015-02-24 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico - CNPq / As vias de reparo por excis?o de base (BER) e por excis?o de nucleot?deo (NER)
desempenham um papel crucial na manuten??o da integridade gen?mica. Polimorfismos em
genes das vias BER e NER, que modulam a capacidade de reparo do DNA, podem estar
relacionados ao risco de desenvolvimento e progn?stico do c?ncer oral. O presente trabalho
teve como objetivo investigar a frequ?ncia de polimorfismos de nucleot?deos simples,
em dois genes da via de reparo do DNA por excis?o de base (XRCC1 ? rs25487 e
APEX1 ? rs1130409) e dois genes da via de reparo por excis?o de nucleot?deo (XPD
? rs13181 e XPF ? rs1799797), em pacientes com carcinoma de c?lulas escamosas
oral (CCEO), buscando associa??es com o risco de desenvolver esta neoplasia
maligna e o seu progn?stico. Um total de 92 amostras de DNA de pacientes com
CCEO e 130 controles foram genotipadas utilizando o m?todo da rea??o em cadeia da
polimerase em tempo real. O software estat?stico GraphPad Prism version 6.0.1. foi utilizado
para a aplica??o dos testes apropriados. Odds ratio (OR) e hazard ratio (HR), e seus
intervalos de confian?a (IC) de 95%, foram calculados pela regress?o log?stica. A avalia??o
do progn?stico foi realizada por meio da curva de Kaplan-Meier e an?lise multivariada de
Cox. A presen?a das variantes polim?rficas nos genes XRCC1, APEX1, XPD, e XPF n?o
foram associadas ao risco de desenvolver CCEO. A intera??o da presen?a da variante
polim?rfica com o h?bito de fumar n?o foi significativa para nenhum dos polimorfismos
analisados. J? a presen?a do polimorfismo em XPD, somada ao h?bito de beber, aumentou
o risco de desenvolver CCEO (OR 1,86, 95% IC: 0,86 ? 4,01, p=0,03). Apenas o SNP do
APEX1 (rs1130409) esteve associado a uma diminui??o da sobrevida espec?fica (HR 3,94,
95% IC: 1,31 ? 11,88, p=0,01). O presente estudo sugere uma intera??o entre o consumo de
?lcool e a presen?a do polimorfismo estudado no gene XPD. Al?m disso, indica um pior
progn?stico para pacientes que possuem o polimorfismo estudado em APEX1. / Base excision repair (BER) and nucleotide excision repair (NER) pathways play
critical role in maintaining genome integrity. Polymorphisms in BER and NER genes
which modulate the DNA repair capacity may affect the susceptibility and prognosis
of oral cancer. This study was conducted with genomic DNA from 92 patients with
oral squamous cell carcinomas (OSCC) and 130 controls. The cases were followed
up to explore the associations between BER and NER genes polymorphisms and the
risk and prognosis of OSCC. Four single-nucleotide polymorphisms (SNPs) in
XRCC1 (rs25487), APEX1 (rs1130409), XPD (rs13181) and XPF (rs1799797) genes
were tested by polymerase chain reaction ? quantitative real time method. The
GraphPad Prism version 6.0.1 statistical software was applied for statistical analysis
of association. Odds ratio (OR), hazard ratio (HR), and their 95 % confidence
intervals (CIs) were calculated by logistic regression. Kaplan-Meier curve and Cox
proportional hazard model were used for prognostic analysis. The presence of
polymorphic variants in XRCC1, APEX1, XPD and XPF genes were not associated
with an increased risk of OSCC. Gene-environment interactions with smoking were
not significant for any polymorphism. The presence of polymorphic variants of the
XPD gene in association with alcohol consumption conferred an increased risk of
1.86 (95% CI: 0.86 ? 4.01, p=0.03) for OSCC. Only APEX1 was associated with
decreased specific survival (HR 3.94, 95% CI: 1.31 ? 11.88, p=0.01). These results
suggest an interaction between polymorphic variants of the XPF gene and alcohol
consumption. Additionally APEX1 may represent a prognostic marker for OSCC.
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.ufrn.br:123456789/19914 |
| Date | 24 February 2015 |
| Creators | Ferreira, Stef?nia Jer?nimo |
| Contributors | 41291824472, http://lattes.cnpq.br/8598456030414229, Costa, Antonio de Lisboa Lopes, 32381611487, http://lattes.cnpq.br/7688226005563390, Lopes, M?rcio Ajudarte, 10209799846, http://lattes.cnpq.br/2554328805208750, Freitas, Roseana de Almeida, 28444361453, http://lattes.cnpq.br/9512014003639405, Soares, S?nia Maria, 29912989449, Galv?o, Hebel Cavalcanti |
| Publisher | Universidade Federal do Rio Grande do Norte, PROGRAMA DE P?S-GRADUA??O EM PATOLOGIA ORAL, UFRN, Brasil |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/doctoralThesis |
| Source | reponame:Repositório Institucional da UFRN, instname:Universidade Federal do Rio Grande do Norte, instacron:UFRN |
| Rights | info:eu-repo/semantics/openAccess |
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