Artículos de revistas
Association Between Genetic Polymorphisms In Dna Mismatch Repair-related Genes With Risk And Prognosis Of Head And Neck Squamous Cell Carcinoma
Registro en:
Association Between Genetic Polymorphisms In Dna Mismatch Repair-related Genes With Risk And Prognosis Of Head And Neck Squamous Cell Carcinoma. Wiley-blackwell, v. 137, p. 810-818 AUG-2015.
0020-7136
WOS:000356428400006
10.1002/ijc.29435
Autor
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
Institución
Resumen
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) 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. 137 4
810 818 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) FAPESP [2012/01807-2] CNPq [401262/2013-8]