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

Paweł Kiczmer; Alicja Prawdzic Seńkowska; Joanna Katarzyna Strzelczyk; Błażej Szydło; Krzysztof Biernacki; Tadeusz Osadnik; Łukasz Krakowczyk; Zofia Ostrowska

doi:10.18388/abp.2017_1613

Paweł Kiczmer Department of medical and molecular Biology, Medical University of Silesia, Zabrze, Poland
Alicja Prawdzic Seńkowska Department of medical and molecular Biology, Medical University of Silesia, Zabrze, Poland
Joanna Katarzyna Strzelczyk Department of medical and molecular Biology, Medical University of Silesia, Zabrze, Poland
Błażej Szydło Department of medical and molecular Biology, Medical University of Silesia, Zabrze, Poland
Krzysztof Biernacki Department of medical and molecular Biology, Medical University of Silesia, Zabrze, Poland
Tadeusz Osadnik 1 2nd Department of Cardiology and Angiology, Silesian Center for Heart Disease, Zabrze, Poland; 2 Genomics Laboratory, Kardio-Med Silesia Science and Technology Park, Zabrze, Poland;
Łukasz Krakowczyk Department of Oncological and Reconstructive Surgery, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland;
Zofia Ostrowska Department of medical and molecular Biology, Medical University of Silesia, Zabrze, Poland

DOI: https://doi.org/10.18388/abp.2017_1613

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.

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