title: DNA repair gene excision repair cross complementing-group 1 (ERCC1) in head and neck squamous cell carcinoma: analysis of methylation and polymorphism (G19007A), protein expression and association with epidemiological and clinicopathological factors.
abstract: OBJECTIVE
  To evaluate the associations of excision repair cross complementing-group 1 (ERCC1) (DNA repair protein) (G19007A) polymorphism, methylation and immunohistochemical expression with epidemiological and clinicopathological factors and with overall survival in head and neck squamous cell carcinoma (HNSCC) patients.
  
  
  RESULTS
  The study group comprised 84 patients with HNSCC who underwent surgery and adjuvant radiotherapy without chemotherapy. Bivariate and multivariate analyses were used. The allele A genotype variant was observed in 79.8% of the samples, GG in 20.2%, GA in 28.6% and AA in 51.2%. Individuals aged more than 45 years had a higher prevalence of the allelic A variant and a high (83.3%) immunohistochemical expression of ERCC1 protein [odds ratio (OR) = 4.86, 95% confidence interval (CI): 1.2-19.7, P = 0.027], which was also high in patients with advanced stage (OR=5.04, 95% CI: 1.07-23.7, P = 0.041). Methylated status was found in 51.2% of the samples, and was higher in patients who did not present distant metastasis (OR = 6.67, 95% CI: 1.40-33.33, P = 0.019) and in patients with advanced stage (OR = 5.04, 95% CI: 1.07-23.7, P = 0.041). At 2 and 5 years, overall survival was 55% and 36%, respectively (median = 30 months).
  
  
  CONCLUSIONS
  Our findings may reflect a high rate of DNA repair due to frequent tissue injury during the lifetime of these individuals, and also more advanced disease presentation in this population with worse prognosis.
authors.affiliation: Department of Radiology, University of São Paulo, São Paulo, Brazil.
authors.forename: Lucianne Maia Costa
authors.initials: LM
authors.lastname: Lima
authors.forename: Ludmilla Regina
authors.initials: LR
authors.lastname: de Souza
authors.forename: Thiago Fonseca
authors.initials: TF
authors.lastname: da Silva
authors.forename: Camila Santos
authors.initials: CS
authors.lastname: Pereira
authors.forename: André Luiz Sena
authors.initials: AL
authors.lastname: Guimarães
authors.forename: Alfredo Maurício Batista
authors.initials: AM
authors.lastname: de Paula
authors.forename: Heloisa
authors.initials: H
authors.lastname: de Andrade Carvalho
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001938:Brazil / Q000453:epidemiology; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000556:secondary / Q000628:therapy; D003131:Combined Modality Therapy; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004720:Endonucleases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D020868:Gene Silencing; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D006801:Humans; D008297:Male; D008745:Methylation; D008875:Middle Aged; D009367:Neoplasm Staging; D012150:Polymorphism, Restriction Fragment Length; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D004268:DNA-Binding Proteins; C071447:ERCC1 protein, human; D004720:Endonucleases