title: 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.
abstract: Metallothioneins (MTs) are low molecular weight, cysteine-rich heavy metal-binding proteins which participate in the mechanisms of Zn homeostasis, and protect against toxic metals. MTs contain metal-thiolate cluster groups and suppress metal toxicity by binding to them. The aim of this study was to determine the -5 A/G (rs28366003) single-nucleotide polymorphism (SNP) in the core promoter region of the MT2A gene and to investigate its effect on allele-specific gene expression and Cd, Zn and Cu content in squamous cell laryngeal cancer (SCC) and non-cancerous laryngeal mucosa (NCM) as a control. The MT2A promoter region -5 A/G SNP was determined by restriction fragment length polymorphism using 323 SCC and 116 NCM. MT2A gene analysis was performed by quantitative real-time PCR. The frequency of A allele carriage was 94.2% and 91.8% in SCC and NCM, respectively, while G allele carriage was detected in 5.8% and 8.2% of SCC and NCM samples, respectively. As a result, a significant association was identified between the -5 A/G SNP in the MT2A gene with mRNA expression in both groups. Metal levels were analyzed by flame atomic absorption spectrometry. The significant differences were identified between A/A and both the A/G and G/G genotypes, with regard to the concentration of the contaminating metal. The Spearman rank correlation results showed that the MT2A expression and Cd, Zn, Cu levels were negatively correlated. Results obtained in this study suggest that -5 A/G SNP in MT2A gene may have an effect on allele-specific gene expression and accumulation of metal levels in laryngeal cancer.
authors.affiliation: I Department of Otolaryngology and Laryngological Oncology, Medical University of Łódź, Kopcinskiego 22, 90-153 Łódź, Poland. Electronic address: katarzyna.starska@umed.lodz.pl.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Starska
authors.affiliation: Department of Cytobiochemistry, University of Łódź, Pomorska 142/143, 90-236 Łódź, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Krześlak
authors.affiliation: Department of Cytobiochemistry, University of Łódź, Pomorska 142/143, 90-236 Łódź, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Forma
authors.affiliation: II Department of Otolaryngology and Laryngological Oncology, Medical University of Łódź, Żeromskiego 113, 90-549 Łódź, Poland.
authors.forename: Jurek
authors.initials: J
authors.lastname: Olszewski
authors.affiliation: Department of Head and Neck Surgery, Medical University of Łódź, Paderewskiego 4, 93-509 Łódź, Poland.
authors.forename: Alina
authors.initials: A
authors.lastname: Morawiec-Sztandera
authors.affiliation: Department of Otolaryngology and Laryngological Oncology, Medical University of Lublin, Jaczewskiego 8, 20-954 Lublin, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Aleksandrowicz
authors.affiliation: Department of Pathology, Medical University of Łódź, Pomorska 251, 92-213 Łódź, Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Lewy-Trenda
authors.affiliation: Department of Cytobiochemistry, University of Łódź, Pomorska 142/143, 90-236 Łódź, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Bryś
mesh_terms: D000368:Aged; D000483:Alleles; D002104:Cadmium / Q000032:analysis; D003300:Copper / Q000032:analysis; D005260:Female; D006801:Humans; D007822:Laryngeal Neoplasms / Q000737:chemistry / Q000235:genetics*; D008297:Male; D008668:Metallothionein / Q000235:genetics*; D019216:Metals, Heavy / Q000032:analysis*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D015032:Zinc / Q000032:analysis
chemical_list: C491053:MT2A protein, human; D019216:Metals, Heavy; D002104:Cadmium; D003300:Copper; D008668:Metallothionein; D015032:Zinc
keywords: Laryngeal cancer; Metallothionein 2A (MT2A); Metals; Single-nucleotide polymorphism (SNP)