IL6 Rs1800795 and MMP9 Rs11697325 Polymorphisms in Vocal Fold Fibroma, Laryngeal Papilloma and Chronic Hyperplastic Laryngitis: A Case–Control Study

Abstract

Background. Vocal fold fibroma and laryngeal papilloma differ in origin, yet both develop on a background of chronic mucosal inflammation and extracellular matrix remodelling. Whether inherited variation in IL6 and MMP9 contributes to these lesions, and whether such a contribution is specific to tumours or shared with chronic hyperplastic laryngitis (CHL), is unknown.
Methods. In this case–control study, 45 patients with histologically verified benign laryngeal tumours (25 fibroma, 20 papilloma), 25 patients with CHL and 30 healthy controls were genotyped for IL6 rs1800795 (−174 G>C) and MMP9 rs11697325 (−8202 A/G) by allele-specific PCR. Allelic, dominant, recessive and additive models were tested; additive models were adjusted for age and sex. A cumulative minor-allele dose (0–4) was analysed, and genotype–phenotype relations were examined in the 70 patients.
Results. All genotype distributions were in Hardy–Weinberg equilibrium. The IL6 C allele was more frequent in tumour patients than in controls (45.6% vs 25.0%; OR 2.51, 95% CI 1.23–5.14, p=0.011), with similar estimates for fibroma (OR 2.36) and papilloma (OR 2.71); the adjusted per-allele OR was 2.18 (1.09–4.35). The MMP9 A allele was not significantly associated with tumours (OR 1.83, 0.90–3.73) but was associated with CHL (OR 2.34, 1.05–5.20, p=0.035). Allele frequencies did not differ between tumours and CHL. Carrying two or more minor alleles across both loci was found in 60.0% of every patient group against 26.7% of controls (OR 4.12, 1.61–10.56, p=0.002). Among patients, the C-allele dose correlated with Voice Handicap Index (ρ=0.30, p=0.011) and the A-allele dose with the number of recurrences (ρ=0.24, p=0.049).
Conclusions. IL6 rs1800795 is associated with benign laryngeal tumours irrespective of histological type, while MMP9 rs11697325 shows its clearest signal in chronic hyperplastic laryngitis. The two variants appear to mark a shared susceptibility to proliferative laryngeal disease, not a tumour-specific risk. The findings are exploratory and need replication in a larger cohort.