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Type: Artigo
Title: Association Between Polymorphisms In Genes Related To Dna Base-excision Repair With Risk And Prognosis Of Oropharyngeal Squamous Cell Carcinoma
Author: Dias Costa
Ericka Francislaine; Santos
Erika Stocco; Liutti
Vitor Teixeira; Leal
Frederico; Antunes Santos
Vivian Castro; Rinck-Junior
Jose Augusto; Viviane Mariano
Fernanda; Malheiros Coutinho-Camillo
Claudia; Altemani
Albina; Passos Lima
Carmen Silvia; Lourenco
Gustavo Jacob
Abstract: 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. 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. 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). 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.
Subject: Oropharyngeal Squamous Cell Carcinoma
Base-excision Repair Pathway
Editor: Springer
New York
Rights: fechado
Identifier DOI: 10.1007/s00432-016-2202-8
Date Issue: 2016
Appears in Collections:Unicamp - Artigos e Outros Documentos

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