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 O-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 χ 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.

The potential role of MGMT rs12917 polymorphism in cancer risk: an updated pooling analysis with 21010 cases and 34018 controls

“…In 2010, Zhong et al [12] performed the first meta-analysis on this topic, reviewing 28 case–control studies from 26 articles [4,5,20,22,23,26–28,31,33–35,37,38,42,45,49,51,52,54,55,59–63]. Another 24 case–control studies [16–19,21,24,25,29,30,32,36,39–41,43,44,46–48,50,53,56–58] were included in our study. We excluded three studies not in-line with the HWE principle [61–63] and one that focussed only on colorectal adenomatous or hyperplastic polyps but not on colorectal cancer [60].…”

“…We excluded one of these studies [64] from our meta-analysis because it did not meet the requirement of full genotype frequency in both case and control groups. Finally, we enrolled another ten case–control studies [4,21,25,29,30,35,36,42,45,48]. In addition, when compared with another meta-analysis of Liu et al (2013) [13], which consisted of 44 case–control studies from 37 articles [4,5,16,17,19,20,22,23,25–27,31–33,35,37,38,42,43,45–47,49,51,52,54–63,65,66], we excluded four studies that were not in HWE [61–63,66], one that did not analyze colorectal cancer [60], and one that included other genetic variants [65].…”

“…In addition, when compared with another meta-analysis of Liu et al (2013) [13], which consisted of 44 case–control studies from 37 articles [4,5,16,17,19,20,22,23,25–27,31–33,35,37,38,42,43,45–47,49,51,52,54–63,65,66], we excluded four studies that were not in HWE [61–63,66], one that did not analyze colorectal cancer [60], and one that included other genetic variants [65]. We also added another 15 new case–control studies [18,21,24,28–30,34,36,39–41,44,48,50,53] for the analysis.…”

MGMT in glial carcinogenesis. Roles from prevention to treatment

“…Paradoxically, this polymorphism is also associated with a reduced risk of endometrial cancers (Sharma et al ., 2009). Even more peculiarly, studies exist for both increased and reduced risk of head and neck carcinomas in subjects carrying rs12917 SNP (Kiczmer et al ., 2018). In similar, while some studies showed no effect of this SNP on lung cancer risk, some other studies showed a risk-increasing effect of this allele (Martínez-Ramírez et al ., 2019; Sharma et al ., 2019).…”

Effects of in IL-1B/IL-1RN variants on the susceptibility to head and neck cancer in a chinese Han population

“…However, not all individuals with these risk factors will eventually develop HNC, which indicates that genetic factors may play a critical role in the carcinogenesis and progression of HNC. Cumulative evidence indicates that genetic variants contribute to the risk of HNC [6][7][8]. However, a large number of risk polymorphisms associated with HNC predisposition have not been discovered.…”