Matrix metalloproteinase-9 (MMP-9) promoter -1562C/T functional polymorphism is associated with an increased risk to develop micropapillary thyroid carcinoma

Abstract

BACKGROUND: Matrix metalloproteinase-9 (MMP-9) is an important mediator of tumor initiation and progression. The MMP-9 promoter -1562C/T functional polymorphism increases gene expression and was identified as a susceptibility factor for various cancers. OBJECTIVE: To evaluate the influence of the MMP-9 promoter genotype on the risk of developing papillary thyroid cancer (PTC) and to correlate cancer patient genotype with the clinical and pathological phenotype. METHODS: We evaluated 236 patients with nodular thyroid disease pre-thyroidectomy (119 benign disease, 117 PTC). Genomic DNA was isolated from whole blood and the MMP-9 -1562C/T genotype was evaluated by PCR-RFLP analysis. RESULTS: Genotype frequencies were in Hardy-Weinberg equilibrium for all groups. The T allele was significantly more frequent in cancer compared to benign disease (17.5% vs 10.1%), p= 0.019. Patients with the CT or CT+TT genotype had an increased risk of developing PTC, specifically micropapillary thyroid carcinoma (MPTC) (CT genotype: OR = 6.467, p= 0.00006; CT+TT: OR = 6.859, p= 0.00002), but not more advanced stages (CT: p= 0.094; CT+TT: p= 0.157). The -1562C/T genotype did not significantly correlate with tumor histological subtype, invasion or TNM stage. CONCLUSION: The MMP-9 -1562C/T functional polymorphism may indicate susceptibility to develop thyroid cancer, specifically intrathyroidal clinically non-relevant MPTC. This suggests that although this genotype might be a predisposing factor, other genetic/epigenetic events are needed for cancer progression.

The Role of Genetic Polymorphisms in Differentiated Thyroid Cancer: A 2023 Update

“…Serum MMP-9 levels measured using an immunometric assay were evaluated in subjects with PTC in a case-control study that concluded that although serum MMP-9 is not helpful in the diagnosis of PTC, a high pre-surgical level might be a prognostic factor that could dictate the treatment aggressiveness [ 60 ]. In a recent study that investigated the role of MMP-9 promoter −1562C/T functional SNP in the risk of developing PTC, the T allele was found significantly more frequently in subjects with PTC (17.5% vs. 10.1%, p = 0.019) [ 61 ]. PTC had an increased risk of developing in subjects with the CT or CT + TT genotype.…”

“…PTC had an increased risk of developing in subjects with the CT or CT + TT genotype. Although MMP-9 promoter SNP seems to increase the susceptibility of developing PTC, it was not associated with tumor histological subtype, invasion, or tumor stage [ 61 ]. Nevertheless, despite these promising results that strongly suggest a role for MMP-9 SNPs in thyroid carcinogenesis, future research is still needed on larger populations.…”