Valor prognóstico de polimorfismos nos genes de reparo do DNA XRCC3 E RAD51 em pacientes com carcinoma epidermóide oral e de orofaringe

• Ano de defesa: 2016
• Autor(a) principal: Santos, Edilmar de Moura
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal do Rio Grande do Norte; Brasil; UFRN; PROGRAMA DE PÓS-GRADUAÇÃO EM PATOLOGIA ORAL
• Palavras-chave em Português: Carcinoma epidermoide oral; Carcinoma epidermoide de orofaringe; Polimorfismos de nucleotídeo único; Reparo de DNA; RAD51; XRCC3; CNPQ::CIENCIAS DA SAUDE: PATOLOGIA ORAL
• Link de acesso: https://repositorio.ufrn.br/jspui/handle/123456789/21272

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.