Association between genetic polymorphisms in DNA mismatch repair‐related genes with risk and prognosis of head and neck squamous cell carcinoma. Issue 4 (26th February 2015)

• Record Type: Journal Article
• Authors: Nogueira, Guilherme Augusto Silva; Lourenço, Gustavo Jacob; Oliveira, Camila Borges Martins; Marson, Fernando Augusto Lima; Lopes‐Aguiar, Leisa; Costa, Ericka Francislaine Dias; Lima, Tathiane Regine Penna; Liutti, Vitor Teixeira; Leal, Frederico; Santos, Vivian Castro Antunes; Rinck‐Junior, José Augusto; Lima, Carmen Silvia Passos
• Is Part Of: International journal of cancer. Volume 137:Issue 4(2015:Aug. 15)
• Page Start: 810
• Page End: 818
• Publication Date: 2015-02-26
• Subjects: Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.29435
• Languages: English
• ISSNs: 0020-7136

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>We examined the influence of <italic>MLH1</italic> c.−93G>A, <italic>MSH2</italic> c.211 + 9C>G, <italic>MSH3</italic> c.3133G>A and <italic>EXO1</italic> 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. <italic>MSH2</italic> GG plus <italic>MSH3</italic> GG (31.7% <italic>vs</italic>. 18.7%, <italic>p</italic> = 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 (<italic>p</italic> = 0.001). At 60 months of follow‐up, relapse‐free survival (RFS) was shorter in patients with <italic>EXO1</italic> GG genotype (54.8% <italic>vs</italic>. 61.1%, <italic>p</italic> = 0.03) and overall survival (OS) was shorter in patients with <italic>MSH3</italic> GG genotype (42.8% <italic>vs</italic>. 52.5%, <italic>p</italic> = 0.02) compared to those with other genotypes, respectively. After multivariate Cox analysis, patients with <italic>EXO1</italic> GG and <italic>MSH3</italic> GG genotypes had worst RFS (HR: 1.50, 95% CI: 1.03–2.20, <italic>p</italic> = 0.03) and OS (HR: 1.59, 95% CI: 1.19–2.13, <italic>P</italic> = 0.002) than those with the remaining genotypes, respectively. Our data present, for the first time, evidence that inherited <italic>MLH1</italic> c.‐93G>A, <italic>MSH2</italic> c.211 + 9C>G, <italic>MSH3</italic> c.3133G>A, and <italic>EXO1</italic> c.1765G>A abnormalities of DNA MMR pathway are important determinants of HNSCC, particularly among smokers, and predictors of patient outcomes.</p> </abstract>