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Rola wybranych polimorfizmów genu MGMT w rozwoju chorób nowotworowych

100%

Kiczmer P., Szydło B., Strzelczyk J. K., Gołąbek K., Ostrowska Z.

Annales Academiae Medicae Silesiensis

2017

vol. 71

378-382

Materiał genetyczny komórki jest nieustannie narażony na działanie czynników mutagennych. Odpowiednie mechanizmy chroniące przed szkodliwym wpływem mutagenów są niezwykle ważne dla prawidłowego funkcjonowania oraz kontroli proliferacji komórek. Jednym z mechanizmów naprawczych jest działanie enzymu MGMT, który odpowiada za ochronę DNA komórki przed czynnikami alkilującymi. Różnice w aktywności enzymu, wynikające z występowania wielu odmian polimorficznych jego genu, mogą prowadzić niekiedy do zwiększonego ryzyka zachorowania na nowotwory. Tematem pracy jest omówienie roli niektórych polimorfizmów genu MGMT w rozwoju oraz terapii chorób nowotworowych.

Cell DNA is constantly exposed to mutagenic factors. DNA repair mechanisms are very important to provide proper cell functioning and proliferation control. One of the DNA repair mechanisms is based on the O6-methylguanine-DNA methyltransferase enzyme, which provides protection against alkylating agents. Differences in MGMT enzyme activity may be caused by MGMT gene polymorphisms. MGMT polymorphisms may increase cancer risk, e.g. lung cancer or esophageal cancer. In this review we have described the role of some MGMT polymorphisms in cancer development and therapy.

The role of MGMT polymorphisms rs12917 and rs11016879 in head and neck cancer risk and prognosis

100%

Kiczmer P., Prawdzic Seńkowska A., Strzelczyk J., Szydło B., Biernacki K., Osadnik T., Krakowczyk Ł., Ostrowska Z.

2018

vol. 65

issue 1

87-92

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 69 HNSCC patients and 242 healthy individuals. Case samples were taken from resected tumour tissue. The control group comprised samples of epithelial cells collected from mucous membranes using swabs. 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 Pearson's χ2 test analysis. Our results indicated that the MGMT rs12917 TT genotype increases the risk of HNSCC. The MGMT rs11016879 AG genotype and A allele were associated with increased HNSCC risk. We noted higher risk of nodal metastasis in rs11016879 AA homozygotes. Mechanisms leading to MGMT enzymatic defect are unknown and hence further studies need to be carried out. Our data suggest that the examined polymorphisms may be considered as potential prognostic factors for HNSCC risk and outcome. Further studies are necessary to verify our results.

Expression profiles of MGMT, p16, and APC genes in tumor and matching surgical margin from patients with oral squamous cell carcinoma

86%

Strzelczyk J., Gołąbek K., Krakowczyk Ł., Owczarek A.

2016

vol. 63

issue 3

505-509

The aim of the study was to assess the expression of MGMT, p16, and APC genes in tumors and matching surgical margin samples from 56 patients with primary OSCC. We also analyzed the association of the clinical variables with the expression of the studied genes. After RNA isolation and cDNA synthesis gene expression levels were assessed by quantitative reverse transcription (qRT)-PCR. Two-sided parametrical Student's t-test for independent groups with equal/unequal variances showed no statistically significant differences in genes' expression in tumor compared to margin samples. No association was found between the genes' expression and clinical parameters, except for MGMT, whose low expression was probably associated with smoking (0.87 vs 1.34, p=0.065). 'Field cancerization' is an area with genetically or epigenetically altered cells and at the same time a risk factor for cancer. Disturbances in gene expression could also be the source of damages leading to cancerization. In conclusion, it is important to mention that the field remaining after a surgery may pose an increased risk of cancer development. It may be suggested that the diagnosis and treatment of cancers should not be concentrated only on the tumor itself, but also on the cancer field effect. Therefore, further molecular analysis on surgical margins and additional research regarding their assessment are required.

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2 Acta Biochimica Polonica

1 Annales Academiae Medicae Silesiensis

1 2018

1 2017

1 2016

2 Gołąbek K.

2 Kiczmer P.

2 Krakowczyk Ł.

2 Ostrowska Z.

2 Strzelczyk J.

2 Szydło B.

1 Biernacki K.

1 Osadnik T.

1 Owczarek A.

1 Prawdzic Seńkowska A.

1 Strzelczyk J. K.

Search results

Rola wybranych polimorfizmów genu MGMT w rozwoju chorób nowotworowych

The role of MGMT polymorphisms rs12917 and rs11016879 in head and neck cancer risk and prognosis

Expression profiles of MGMT, p16, and APC genes in tumor and matching surgical margin from patients with oral squamous cell carcinoma