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

Histopathology. 2012 Feb;60(3):489-96. doi: 10.1111/j.1365-2559.2011.04062.x. Epub 2011 Dec 16.

Abstract

Aims: 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.

Methods and 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).

Conclusion: 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.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Brazil / epidemiology
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / secondary
  • Carcinoma, Squamous Cell / therapy
  • Combined Modality Therapy
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Endonucleases / genetics*
  • Endonucleases / metabolism
  • Female
  • Gene Frequency
  • Gene Silencing
  • Genotype
  • Head and Neck Neoplasms / genetics*
  • Head and Neck Neoplasms / mortality
  • Head and Neck Neoplasms / pathology
  • Head and Neck Neoplasms / therapy
  • Humans
  • Male
  • Methylation
  • Middle Aged
  • Neoplasm Staging
  • Polymorphism, Restriction Fragment Length*
  • Retrospective Studies
  • Survival Rate

Substances

  • DNA-Binding Proteins
  • ERCC1 protein, human
  • Endonucleases