Metallothionein 2A core promoter region genetic polymorphism and its impact on the risk, tumor behavior, and recurrences of sinonasal inverted papilloma (Schneiderian papilloma)

Katarzyna Starska, Magdalena Bryś, Ewa Forma, Jurek Olszewski, Piotr Pietkiewicz, Iwona Lewy-Trenda, Olga Stasikowska-Kanicka, Marian Danilewicz, Anna Krześlak

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.