title: XPD c.934G>A polymorphism of nucleotide excision repair pathway in outcome of head and neck squamous cell carcinoma patients treated with cisplatin chemoradiation.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
authors.forename: Leisa
authors.initials: L
authors.lastname: Lopes-Aguiar
authors.affiliation: Department of Internal Medicine, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
authors.forename: Ericka Francislaine Dias
authors.initials: EF
authors.lastname: Costa
authors.affiliation: Department of Internal Medicine, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
authors.forename: Guilherme Augusto Silva
authors.initials: GA
authors.lastname: Nogueira
authors.affiliation: Department of Internal Medicine, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
authors.forename: Tathiane Regine Penna
authors.initials: TR
authors.lastname: Lima
authors.affiliation: Department of Clinical Pathology, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
authors.forename: Marília Berlofa
authors.initials: MB
authors.lastname: Visacri
authors.affiliation: Department of Internal Medicine, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
authors.forename: Eder Carvalho
authors.initials: EC
authors.lastname: Pincinato
authors.affiliation: Department of Ophthalmology and Otorhinolaryngology, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
authors.forename: Luciane
authors.initials: L
authors.lastname: Calonga
authors.affiliation: Department of Pathology, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
authors.forename: Fernanda Viviane
authors.initials: FV
authors.lastname: Mariano
authors.affiliation: Department of Pathology, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
authors.forename: Albina Messias
authors.initials: AM
authors.lastname: de Almeida Milani Altemani
authors.affiliation: Department of Radiology, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
authors.forename: João Maurício Carrasco
authors.initials: JM
authors.lastname: Altemani
authors.affiliation: Department of Pathology, A.C. Camargo Cancer Center, São Paulo, São Paulo, Brazil.
authors.forename: Cláudia Malheiros
authors.initials: CM
authors.lastname: Coutinho-Camillo
authors.affiliation: Department of Internal Medicine, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
authors.forename: Maria Almerinda Vieira Fernandes
authors.initials: MA
authors.lastname: Ribeiro Alves
authors.affiliation: Department of Clinical Pathology, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Moriel
authors.affiliation: Department of Radiology, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
authors.forename: Celso Dario
authors.initials: CD
authors.lastname: Ramos
authors.affiliation: Department of Ophthalmology and Otorhinolaryngology, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
authors.forename: Carlos Takahiro
authors.initials: CT
authors.lastname: Chone
authors.affiliation: Department of Internal Medicine, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
authors.forename: Carmen Silvia Passos
authors.initials: CS
authors.lastname: Lima
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics; D002945:Cisplatin / Q000009:adverse effects / Q000627:therapeutic use*; D004260:DNA Repair; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006239:Haplotypes; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009325:Nausea / Q000139:chemically induced; D009503:Neutropenia / Q000139:chemically induced; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D011446:Prospective Studies; D015398:Signal Transduction / Q000235:genetics; D014839:Vomiting / Q000139:chemically induced; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human; D002945:Cisplatin
keywords: cisplatin; head and neck squamous cell carcinoma; nucleotide excision repair pathway; outcome; single nucleotide polymorphisms