title: Association between polymorphisms in genes related to DNA base-excision repair with risk and prognosis of oropharyngeal squamous cell carcinoma.
abstract: OBJECTIVE
  We examined the influence of OGG1 c.977C>G (rs1052133), APEX1 c.444T>G (rs1130409), XRCC1 c.-77T>C (rs3213245), c.580C>T (rs1799782), c.839G>A (rs25489) and c.1196G>A (rs25487) single-nucleotide polymorphisms (SNPs), involved in base-excision repair (BER) pathway, on oropharyngeal squamous cell carcinoma (OPSCC) risk and prognosis.
  
  
  METHODS
  Aiming to identify the genotypes, DNA from 200 consecutive OPSCC patients and 200 controls was analyzed by PCR-RFLP. The prognostic impact of genotypes of SNPs on progression-free survival (PFS) and overall survival of OPSCC patients was examined using the Kaplan-Meier estimates and Cox regression analyses.
  
  
  RESULTS
  XRCC1 c.580CT or TT genotypes (19.5 vs. 11.0 %, P = 0.04) and XRCC1 TTGG haplotype from c.-77T>C, c.580C>T, c.839G>A and c.1196G>A SNPs (17.5 vs. 10.0 %, P = 0.04) were more common in patients with OPSCC than in controls. Carriers of combined genotypes of c.580C>T and TTGG haplotype of XRCC1 gene were under 3.35- and 3.22-fold increased risk of OPSCC than others. For survival analysis, we selected only patients with tumor at stage IV. The median follow-up time was 24.5 months. At 24 months of follow-up, PFS was shorter in patients with OGG1 c.977CC genotype when compared with others genotypes (35.5 vs. 52.1 %, log-rank test, P = 0.03). After multivariate Cox analysis, patients with OGG1 c.977CC genotype had more chance to present tumor progression when compared with others (HR 1.68, P = 0.02).
  
  
  CONCLUSIONS
  Our data present, for the first time, evidence that inherited OGG1 c.977C>G; XRCC1 c.-77T>C, c.580C>T, c.839G>A and c.1196G>A abnormalities of DNA BER pathway are important determinants of OPSCC and predictors of patient outcomes.
authors.affiliation: Laboratory of Cancer Genetics, Faculty of Medical Sciences, University of Campinas, Rua Vital Brasil, 50, Cidade Universitária "Zeferino Vaz", Distrito de Barão Geraldo, Campinas, São Paulo, CEP: 13083-888, Brazil.
authors.forename: Ericka Francislaine Dias
authors.initials: EF
authors.lastname: Costa
authors.affiliation: Laboratory of Cancer Genetics, Faculty of Medical Sciences, University of Campinas, Rua Vital Brasil, 50, Cidade Universitária "Zeferino Vaz", Distrito de Barão Geraldo, Campinas, São Paulo, CEP: 13083-888, Brazil.
authors.forename: Erika Stocco
authors.initials: ES
authors.lastname: Santos
authors.affiliation: Laboratory of Cancer Genetics, Faculty of Medical Sciences, University of Campinas, Rua Vital Brasil, 50, Cidade Universitária "Zeferino Vaz", Distrito de Barão Geraldo, Campinas, São Paulo, CEP: 13083-888, Brazil.
authors.forename: Vitor Teixeira
authors.initials: VT
authors.lastname: Liutti
authors.affiliation: Laboratory of Cancer Genetics, Faculty of Medical Sciences, University of Campinas, Rua Vital Brasil, 50, Cidade Universitária "Zeferino Vaz", Distrito de Barão Geraldo, Campinas, São Paulo, CEP: 13083-888, Brazil.
authors.forename: Frederico
authors.initials: F
authors.lastname: Leal
authors.affiliation: Laboratory of Cancer Genetics, Faculty of Medical Sciences, University of Campinas, Rua Vital Brasil, 50, Cidade Universitária "Zeferino Vaz", Distrito de Barão Geraldo, Campinas, São Paulo, CEP: 13083-888, Brazil.
authors.forename: Vivian Castro Antunes
authors.initials: VC
authors.lastname: Santos
authors.affiliation: Laboratory of Cancer Genetics, Faculty of Medical Sciences, University of Campinas, Rua Vital Brasil, 50, Cidade Universitária "Zeferino Vaz", Distrito de Barão Geraldo, Campinas, São Paulo, CEP: 13083-888, Brazil.
authors.forename: José Augusto
authors.initials: JA
authors.lastname: Rinck-Junior
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, 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 Pathology, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
authors.forename: Albina
authors.initials: A
authors.lastname: Altemani
authors.affiliation: Laboratory of Cancer Genetics, Faculty of Medical Sciences, University of Campinas, Rua Vital Brasil, 50, Cidade Universitária "Zeferino Vaz", Distrito de Barão Geraldo, Campinas, São Paulo, CEP: 13083-888, Brazil.
authors.forename: Carmen Silvia Passos
authors.initials: CS
authors.lastname: Lima
authors.affiliation: Laboratory of Cancer Genetics, Faculty of Medical Sciences, University of Campinas, Rua Vital Brasil, 50, Cidade Universitária "Zeferino Vaz", Distrito de Barão Geraldo, Campinas, São Paulo, CEP: 13083-888, Brazil. gutolour@fcm.unicamp.br.
authors.forename: Gustavo Jacob
authors.initials: GJ
authors.lastname: Lourenço
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000235:genetics*; D045647:DNA Glycosylases / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012307:Risk Factors; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase
keywords: Base-excision repair pathway; Oropharyngeal squamous cell carcinoma; Polymorphisms; Prognosis; Risk