XPD c.934G > A polymorphism of nucleotide excision repair pathway in outcome of head and neck squamous cell carcinoma patients treated with cisplatin chemoradiation

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Lopes-Aguiar, Leisa ; Dias Costa, Ericka Francislaine ; Silva Nogueira, Guilherme Augusto ; Penna Lima, Tathiane Regine ; Visacri, Marilia Berlofa ; Pincinato, Eder Carvalho ; Calonga, Luciane ; Mariano, Fernanda Viviane ; de Almeida Milani Altemani, Albina Messias ; Carrasco Altemani, Joao Maurcio ; Coutinho-Camillo, Claudia Malheiros ; Fernandes Ribeiro Alves, Maria Almerinda Vieira ; Moriel, Patricia ; Ramos, Celso Dario ; Chone, Carlos Takahiro ; Passos Lima, Carmen Silvia

• Tipo de documento: Artigo Científico
• Fonte: ONCOTARGET; v. 8, n. 10, p. 16190-16201, 2017.
• Citações Web of Science: 7

Resumo

This study aimed to investigate the associations of XPC c.2815A>C, XPD c.934G>A and c.2251A>C, XPF c.2505T>C and ERCC1 c.354C>T single nucleotide polymorphisms (SNPs) of nucleotide excision repair pathway in outcome of head and neck squamous cell carcinoma (HNSCC) patients treated with cisplatin (CDDP) chemoradiation. Patients with XPC c.2815AC or CC and XPD c.934GA or AA genotypes had 0.20 and 0.38 less chances of presenting moderate/severe ototoxicity and nausea, respectively. Patients with XPD c.934AA and c.2251AC or CC genotypes had 8.64, 12.29 and 3.55 more chances of achieving complete response (CR), consistent ototoxicity and nephrotoxicity, respectively. AA haplotype of XPD and ACT haplotype of XPD and ERCC1 SNPs were associated with 9.30 and 3.41 more chances of achieving CR and consistent nephrotoxicity, respectively. At 24 months of follow-up, patients with XPD c.934AA genotype presented lower progression-free survival and overall survival in Kaplan-Meier estimates, and differences between groups remained the same in univariate Cox analysis. Patients with XPD c.934AA genotype had 2.13 and 2.04 more risks of presenting tumor progression and death than others in multivariate Cox analysis. Our data present preliminary evidence that XPC c.2815A>C, XPD c.934G>A and c.2251A>C, and ERCC1 c.354C>T SNPs alter outcome of HNSCC patients treated with CDDP chemoradiation. (AU)

• Processo FAPESP: 11/15089-1 - Polimorfismos em Genes de Reparo de DNA na Farmacogenética da Cisplatina Associada à Radioterapia em Portadores de Carcinoma de Células Escamosas de Cabeça e Pescoço
• Beneficiário: Leisa Lopes Aguiar
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 12/01807-2 - Farmacogenética da cisplatina em portadores de carcinoma de células escamosas de cabeça e pescoço
• Beneficiário: Carmen Silvia Passos Lima
• Modalidade de apoio: Auxílio à Pesquisa - Regular