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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Leisa Lopes-Aguiar1, Ericka Francislaine Dias Costa1, Guilherme Augusto Silva Nogueira1, Tathiane Regine Penna Lima1, Marília Berlofa Visacri2, Eder Carvalho Pincinato1, Luciane Calonga3, Fernanda Viviane Mariano4, Albina Messias de Almeida Milani Altemani4, João Maurício Carrasco Altemani5, Cláudia Malheiros Coutinho-Camillo6, Maria Almerinda Vieira Fernandes Ribeiro Alves1, Patrícia Moriel2, Celso Dario Ramos5, Carlos Takahiro Chone3, Carmen Silvia Passos Lima1
1Department of Internal Medicine, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil
2Department of Clinical Pathology, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil
3Department of Ophthalmology and Otorhinolaryngology, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil
4Department of Pathology, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil
5Department of Radiology, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil
6Department of Pathology, A.C. Camargo Cancer Center, São Paulo, São Paulo, Brazil
Carmen Silvia Passos Lima, e-mail: firstname.lastname@example.org
Keywords: head and neck squamous cell carcinoma, cisplatin, nucleotide excision repair pathway, single nucleotide polymorphisms, outcome
Received: October 30, 2015 Accepted: February 16, 2016 Published: February 24, 2016
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.
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