The role of MGMT polymorphisms (Rs12917 and Rs11016879) in head and neck cancer risk and prognosis

Abstract

Head and neck squamous cell carcinoma (HNSCC) is one of the leading cancers by incidence worldwide. The risk of these cancers is strictly associated with alkylation factors present in tobacco smoke. The crucial role in preventing DNA alkylation is played by O6-methylguanine-DNA methyltransferase (MGMT). Dysfunction or lack of MGMT is associated with an increased risk of cancer. The aim of the study was to assess the influence of MGMT polymorphisms: Rs12917 and Rs11016879 on HNSCC risk and course. The study consisted of 42 HNSCC patients and 58 healthy individuals. Case samples were taken from resected tumour tissue. The control group comprised samples of epithelial cells collected from mucous membranes using swabs. To analyse the SNPs we performed Real-Time PCR. DNA samples were genotyped by employing the 5' nuclease assay for allelic discrimination using TaqMan SNP Genotyping Assays. The significance between distributions of genotypes and alleles was tested using the Pearson’s χ2 test analysis. The MGMT Rs12917 TT genotype was observed only in the HNSCC patients. In case of Rs11016879 no increase in the risk was observed (p>0.05). However, we noted higher risk of nodal metastasis in Rs11016879 homozygotes [OR=10.67 (95% CI=0.36-23.93), p=0.03]. Our findings suggest that MGMT gene polymorphisms may play an important role in risk and prognosis of HNSCC. Mechanisms leading to MGMT enzymatic defect remain unknown and hence further studies need to be carried out into this topic.