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Previous issue date: 2016-02-24 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico (CNPq) / Falhas nos genes respons?veis por reparos no DNA podem influenciar no surgimento de c?ncer ou afetar a resposta aos tratamentos. Estudos t?m demonstrado que a varia??o na capacidade de reparo do DNA pode ser resultado de polimorfismos funcionais nestes genes, e alguns destes experimentos sugerem que a presen?a de polimorfismos de nucleot?deos simples (SNPs), em genes de reparo, est? relacionada ao desenvolvimento e resposta ao tratamento de v?rios c?nceres, incluindo o Carcinoma Epidermoide Oral (CEO) e o Carcinoma Epidermoide de Orofaringe (CEOR). Nesta pesquisa avaliou-se a frequ?ncia de tr?s SNPs em dois genes de reparo do DNA RAD51 172G>T (c.-61 G>T, rs1801321), RAD51 135G>C (c.-98 G>C, rs1801320) e XRCC3 T241M (c. 722 C>T, rs861539) em indiv?duos saud?veis (n=130) e indiv?duos com CEO e CEOR (n=126) e investigou-se poss?veis rela??es de tais achados com os desfechos cl?nicos: resposta tumoral ao tratamento com radioterapia e quimioterapia, recidiva, e sobrevida global. Constatou-se frequ?ncia al?lica e genot?pica em equil?brio. A presen?a dos SNPs analisados n?o revelou ser um fator de risco para o desenvolvimento de CEO ou CEOR; contudo, quando associado ao h?bito de fumar ou beber, aumentou o risco de desenvolver o c?ncer de tr?s a cento e cinquenta vezes (p<000,1). A resposta tumoral ao tratamento de radioterapia e quimioterapia foi semelhante nos pacientes com ou sem SNPs. Nenhum polimorfismo demonstrou signific?ncia estat?stica em rela??o ? sobrevida livre de recidiva ou sobrevida global. Os gen?tipos AA e AC do SNP rs861539 no gene XRCC3, os gen?tipos CC e CG do SNP rs1801320 e GG e GT do SNP 1801321 no gene RAD51, aumentam o risco do desenvolvimento de carcinoma epidermoide oral e de orofaringe, quando associados ao h?bito de beber ou fumar. Os polimorfismos estudados nos genes XRCC3 e RAD51 n?o est?o associados ? resposta ? radioterapia, sobrevida livre de recidiva ou sobrevida global. / Faults in the genes responsible for repairs to the DNA can influence the onset of
cancer or affect the response to treatment. This research evaluated the frequency of
three single nucleotide polymorphisms (SNPs) in two repair genes DNA RAD51
172g> T (rs1801321), RAD51 135G> C (rs1801320) and XRCC3 T241M (rs861539)
in individuals without cancer (n = 130) and patients with oral squamous cell
carcinoma (OSC) and carcinoma oropharyngeal squamous (ORSC) (n = 126) and
investigated possible relationships of these findings with clinical and pathological
data and clinical outcomes: tumor response to radiotherapy and chemotherapy,
disease-free survival, and overall survival. It was found that the allele and genotype
frequencies were in equilibrium Hard-Weinberg equilibrium. The presence of at least
one polymorphic allele in XRCC3 (rs861539) gene is associated with histological
grade (WHO) higher (p = 0.007). We observed a higher recurrence rate trend (p =
0.08) and more advanced stage (p = 0.08) in the group that had at least one
polymorphic allele of RAD51 gene (rs1801321). The presence of the analyzed SNPs
not proved to be a risk factor for the development of CEO or CEOR; however, when
combined with smoking or drinking, increased the risk of developing cancer from
three to one hundred and fifty times. The tumor response to radiotherapy and
chemotherapy was similar in patients with and without SNPs. No polymorphism
showed statistical significance in relation to recurrence-free survival or overall
survival. We conclude that the presence of at least one polymorphic allele of the
SNPs rs861539 in XRCC3 gene, rs1801320 and rs1801321 in the RAD51 gene
increase the risk of development of OSC and ORSC, when associated with the habit
of drinking or smoking. Polymorphisms studied in XRCC3 and RAD51 genes are not
associated with response to radiation therapy, relapse-free survival or overall
survival.
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.ufrn.br:123456789/21272 |
| Date | 24 February 2016 |
| Creators | Santos, Edilmar de Moura |
| Contributors | 28444361453, http://lattes.cnpq.br/9512014003639405, Nonaka, Cassiano Francisco Weege, 02781932426, http://lattes.cnpq.br/0224522010734716, Galv?o, Hebel Cavalcanti, 41291824472, http://lattes.cnpq.br/8598456030414229, Miguel, Marcia Cristina da Costa, 82134731400, http://lattes.cnpq.br/9634115210679435, Leit?o, ?guida Cristina Gomes Henriques, 03973092443, http://lattes.cnpq.br/2563401100488039, Freitas, Roseana de Almeida |
| 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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