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.
Highlights
Sinonasal inverted papillomas (Schneiderian papillomas) of the nasal cavity and paranasal sinuses are unique, locally aggressive, primarily benign epithelial neoplasms derived from the Schneiderian membrane with an endophytic growth pattern and proliferation in the underlying stroma
The findings suggest that Metallothionein 2A (MT2A) gene variation rs28366003 may be implicated in the etiology of sinonasal inverted papilloma in a Polish population
All patients had received a confirmed diagnosis of inverted papilloma (IP) based on histopathological evaluation and had undergone functional endoscopic sinonasal surgery (FESS), this was dependent on the extent of neoplastic lesions described by CT scans of nasal cavity and paranasal sinuses performed before surgery and assessed during an earlier FESS procedure
Summary
Sinonasal inverted papillomas (Schneiderian papillomas) of the nasal cavity and paranasal sinuses are unique, locally aggressive, primarily benign epithelial neoplasms derived from the Schneiderian membrane with an endophytic growth pattern and proliferation in the underlying stroma. The metallothioneins (MTs) family of low molecular mass (6–7 kDa) proteins is a family of metal-binding and metalabsorbing, cysteine-rich molecules which affect the homeostasis of intracellular metals such as cadmium, lead, mercury, zinc, and copper [5,6,7]. MTs are involved in many pathophysiological processes including metal detoxification, cell proliferation, apoptosis, and deactivation of reactive oxygen species [5,6,7,8]. The transcription of the MT gene is activated in response to a wide range of stimuli, including oxidative stressinducing agents, cytokines, hormones and various chemical agents, as well as Cd and Zn in particular [5, 6, 9, 10]. MTF-1 exerts effects on MT gene transcription by independent increase in MTF-1 DNA-binding activity [12, 13]
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