The −5 A/G single-nucleotide polymorphism in the core promoter region of MT2A and its effect on allele-specific gene expression and Cd, Zn and Cu levels in laryngeal cancer

The effect of metallothionein 2A core promoter region single-nucleotide polymorphism on accumulation of toxic metals in sinonasal inverted papilloma tissues

“…Similarly, other researchers report an increased level of Cu in untreated carcinomas of the head and neck (Büntzel et al, 2003;Kosova et al, 2012), which resembles our previous findings in a laryngeal cancer population (Starska et al, 2014a). Interestingly, while Krześlak et al (2013) describe very similar results to those given in the present study and confirm that individuals with tumors may be more sensitive to Cu toxicity, other authors observe decreased or no significant differences in concentration relative to controls (Akçil et al, 2004;Reddy et al, 2002).…”

“…However, in contrast to the results given above for heterozygotes of the major allele and atypical homozygotes, a considerably high accumulation of both Cd and Cu in IP tissue was reported. These changes in toxic metal levels in neoplastic tissue remain in line with our recent studies on laryngeal cancer, which note that − 5 A/G SNP in the MT2A gene may be related to Cd, Zn and Cu content (Starska et al, 2014a).…”

“…A literature review reveals few, and often contradictory, results concerning both Cd concentration in neoplastic and non-cancerous tissues, as well as the relationship between the presence of cadmium ions and the risk of human tumors and patient outcome (Krześlak et al, 2013;Navarro and Rohan, 2007;Sarafanov et al, 2011;Starska et al, 2014a). Most research confirms the association between Cd and higher mortality and frequency of recurrence rate, although additional prospective studies are needed (Navarro and Rohan, 2007;Park et al, 2012).…”

“…Metallothionein expression is known to be induced by various heavy metals, inter alia Zn ions, and an association has been noted between Zn content and MT2A expression or the presence of the MT2A rs28366003 SNP (Kayaalti et al, 2010(Kayaalti et al, , 2011Krześlak et al, 2013;Starska et al, 2014a). Similarly, Krześlak et al (2013) report an elevated Zn level in individuals with G allele carriage compared with homozygote typical, and suggest that disturbances in MT2A expression can affect Zn accumulation in tumor cells.…”

“…Unfortunately, the results of studies concerning the associations between the level of toxic metals and metallic agents with either pathological tumor features and disease outcome or cancer risk, have been contradictory, and no firm conclusions can be drawn from them (Basu et al, 2013;Oddone et al, 2014;Park et al, 2012;Sivulka and Seilkop, 2009). Moreover, a literature survey reveals only individual studies related to these parameters in head and neck region neoplasms and none to sinonasal inverted papilloma (Akinmoladun et al, 2013;Kosova et al, 2012;Starska et al, 2014a). Therefore, more research is needed to better understand the possible biological mechanisms of development and the role of both MTs and toxic metals in this rare, locally aggressive tumorigenic process.…”