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Type: Artigo
Title: Association between genetic polymorphisms in DNA mismatch repair-related genes with risk and prognosis of head and neck squamous cell carcinoma
Author: Silva Nogueira, Guilherme Augusto
Lourenco, Gustavo Jacob
Martins Oliveira, Camila Borges
Lima Marson, Fernando Augusto
Lopes-Aguiar, Leisa
Dias Costa, Ericka Francislaine
Penna Lima, Tathiane Regine
Liutti, Vitor Teixeira
Leal, Frederico
Antunes Santos, Vivian Castro
Rinck-Junior, Jose Augusto
Passos Lima, Carmen Silvia
Abstract: We examined the influence of MLH1 c.-93G>A, MSH2 c.211 + 9C>G, MSH3 c.3133G>A and EXO1 c.1765G>A polymorphisms, involved in DNA mismatch repair (MMR), on head and neck (HN) squamous cell carcinoma (SCC) risk and prognosis. Aiming to identify genotypes, DNA from 450 HNSCC patients and 450 controls was analyzed by PCR-RFLP or real time PCR. MSH2 GG plus MSH3 GG (31.7% vs. 18.7%, p = 0.003) genotypes were higher in laryngeal SCC (LSCC) patients than in controls. Carriers of the respective combined genotype were under a 3.69 (95% CI: 1.54-8.81)-fold increased risk of LSCC. Interactions of tobacco and tobacco plus all the above-mentioned polymorphisms on HNSCC and LSCC risk were also evident in study (p = 0.001). At 60 months of follow-up, relapse-free survival (RFS) was shorter in patients with EXO1 GG genotype (54.8% vs. 61.1%, p = 0.03) and overall survival (OS) was shorter in patients with MSH3 GG genotype (42.8% vs. 52.5%, p = 0.02) compared to those with other genotypes, respectively. After multivariate Cox analysis, patients with EXO1 GG and MSH3 GG genotypes had worst RFS (HR: 1.50, 95% CI: 1.03-2.20, p = 0.03) and OS (HR: 1.59, 95% CI: 1.19-2.13, P = 0.002) than those with the remaining genotypes, respectively. Our data present, for the first time, evidence that inherited MLH1 c.-93G>A, MSH2 c.211 + 9C>G, MSH3 c.3133G>A, and EXO1 c.1765G>A abnormalities of DNA MMR pathway are important determinants of HNSCC, particularly among smokers, and predictors of patient outcomes
Subject: Carcinoma de células escamosas de cabeça e pescoço
Country: Estados Unidos
Editor: John Wiley & Sons
Rights: Fechado
Identifier DOI: 10.1002/ijc.29435
Date Issue: 2015
Appears in Collections:IB - Artigos e Outros Documentos
FCM - Artigos e Outros Documentos

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