title: Metallothionein 2A core promoter region genetic polymorphism and its impact on the risk, tumor behavior, and recurrences of sinonasal inverted papilloma (Schneiderian papilloma).
abstract: Inverted papillomas are a unique group of locally aggressive benign epithelial neoplasms in the nasal cavity and paranasal sinuses arising from the Schneiderian mucosa. Metallothioneins are sulfhydryl-rich heavy metal-binding proteins required for metal toxicity protection and regulation of biological mechanisms including proliferation and invasion. The goal of this study was to identify three SNPs at loci -5 A/G (rs28366003) and -209 A/G (rs1610216) in the core promoter region and at locus +838 C/G (rs10636) in 3'UTR region of the MT2A gene with IP risk and with tumor invasiveness according to Krouse staging. Genotyping was performed using the PCR restriction fragment length polymorphism technique in 130 genetically unrelated IP individuals, and 418 randomly selected healthy volunteers. The presence of the rs28366003 SNP was significantly related to the risk of IP within the present population-based case-control study. Compared to homozygous common allele carriers, heterozygosity and homozygosity for the G variant had a significantly increased risk of IP (adjusted odds ratio [OR] = 7.71, 95% confidence interval [CI]: 4.01-14.91, p(dominant) < 0.001). Moreover, risk allele carriers demonstrated higher Krouse stage (pT1 vs. pT2-4) (OR = 19.32; 95% CI, 2.30-173.53; p < 0.0001), diffuse tumor growth (OR = 4.58; 95% CI, 1.70-12.11; p = 0.0008), bone destruction (OR = 4.13; 95% CI, 1.50-11.60; p = 0.003), and higher incidence of tumor recurrences (OR = 5.11; 95% CI, 1.68-15.20; p = 0.001). The findings suggest that MT2A gene variation rs28366003 may be implicated in the etiology of sinonasal inverted papilloma in a Polish population.
authors.affiliation: I Department of Otolaryngology and Laryngological Oncology, Medical University of Łódź, Kopcinskiego 22, 90-153, Łódź, Poland. 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: Magdalena
authors.initials: M
authors.lastname: Bryś
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: II Department of Otolaryngology and Laryngological Oncology, Medical University of Łódź, Żeromskiego 113, 90-549, Łódź, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Pietkiewicz
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 Pathology, Medical University of Łódź, Pomorska 251, 92-213, Łódź, Poland.
authors.forename: Olga
authors.initials: O
authors.lastname: Stasikowska-Kanicka
authors.affiliation: Department of Pathology, Medical University of Łódź, Pomorska 251, 92-213, Łódź, Poland.
authors.forename: Marian
authors.initials: M
authors.lastname: Danilewicz
authors.affiliation: Department of Cytobiochemistry, University of Łódź, Pomorska 142/143, 90-236, Łódź, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Krześlak
mesh_terms: D000328:Adult; D000368:Aged; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008668:Metallothionein / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology / Q000821:virology; D009669:Nose Neoplasms / Q000235:genetics* / Q000473:pathology; D018308:Papilloma, Inverted / Q000235:genetics* / Q000473:pathology; D030361:Papillomavirus Infections / Q000235:genetics / Q000473:pathology / Q000821:virology; D010256:Paranasal Sinuses / Q000473:pathology; D011044:Poland; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
chemical_list: C491053:MT2A protein, human; D008668:Metallothionein
keywords: IP; Krouse staging system; Metallothionein 2A (MT2A); Recurrences; Single-nucleotide polymorphism (SNP); Sinonasal inverted papilloma (Schneiderian papilloma)