doctoralThesis
Avaliação de polimorfismos funcionais nos genes de reparo XRCC1, APEX1, XPD e XPF em carcinomas de células escamosas orais
Fecha
2015-02-24Registro en:
FERREIRA, Stefânia Jerônimo. Avaliação de polimorfismos funcionais nos genes de reparo XRCC1, APEX1, XPD e XPF em carcinomas de células escamosas orais. 2015. 117f. Tese (Doutorado em Patologia Oral) - Centro de Ciências da Saúde, Universidade Federal do Rio Grande do Norte, Natal, 2015.
Autor
Ferreira, Stefânia Jerônimo
Resumen
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.