Association between genetic polymorphisms in DNA mismatch repair-related genes with risk and prognosis of head and neck squamous cell carcinoma
| Autor: | Guilherme Augusto Silva, Nogueira, Gustavo Jacob, Lourenço, Camila Borges Martins, Oliveira, Fernando Augusto Lima, Marson, Leisa, Lopes-Aguiar, Ericka Francislaine Dias, Costa, Tathiane Regine Penna, Lima, Vitor Teixeira, Liutti, Frederico, Leal, Vivian Castro Antunes, Santos, José Augusto, Rinck-Junior, Carmen Silvia Passos, Lima |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
Aged 80 and over Male Adolescent Genotype Squamous Cell Carcinoma of Head and Neck Nuclear Proteins Middle Aged Prognosis Polymorphism Single Nucleotide Disease-Free Survival DNA-Binding Proteins DNA Repair Enzymes Exodeoxyribonucleases MutS Homolog 2 Protein Head and Neck Neoplasms MutS Homolog 3 Protein Carcinoma Squamous Cell Humans Female Neoplasm Recurrence Local MutL Protein Homolog 1 Genetic Association Studies Adaptor Proteins Signal Transducing Aged |
| Zdroj: | International journal of cancer. 137(4) |
| ISSN: | 1097-0215 |
| Popis: | We examined the influence of MLH1 c.-93GA, MSH2 c.211 + 9CG, MSH3 c.3133GA and EXO1 c.1765GA 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.-93GA, MSH2 c.211 + 9CG, MSH3 c.3133GA, and EXO1 c.1765GA abnormalities of DNA MMR pathway are important determinants of HNSCC, particularly among smokers, and predictors of patient outcomes. |
| Databáze: | OpenAIRE |
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