GENETIC PREDISPOSITION TO THE RISK OF POTENTIALLY MALIGNANT AND MALIGNANT DISEASES OF THE HEAD AND NECK, EGFR A2073T RECEPTOR GENE POLYMORPHISM

Abstract

Single-nucleotide polymorphisms (SNPs) in the epidermal growth factor receptor (EGFR) gene are considered key determinants of individual susceptibility to premalignant oral lesions and head-and-neck squamous-cell carcinoma (HNSCC), diseases in which aberrant EGFR signalling is almost ubiquitous. The purpose of the study was investigate the association of the EGFR A2073T SNP (rs2227984) with oral leukoplakia and HNSCC. Materials and methods. A total of 60 subjects aged 25–55 years were enrolled: leukoplakia (n = 20), HNSCC (n = 20) and healthy controls (n = 20). Genomic DNA was extracted from buccal epithelial cells using a modified Chelex protocol. Genotyping of A2073T was performed by allele-specific polymerase chain reaction. Genotype and allele distributions were analysed with Pearson’s χ² test; associations were expressed as odds ratios (OR) with 95 % confidence intervals (CI). Statistical significance was set at p < 0,05.Research results. Genotype frequencies conformed to Hardy–Weinberg equilibrium in all cohorts. In both the dominant and codominant inheritance models, carriage of the A allele (genotypes AA / AT) was strongly associated with HNSCC (OR = 11.111; 95 % CI 1.395–88.521; χ² = 6.240; p = 0.013). Conversely, the homozygous mutant genotype TT exerted a protective effect against leukoplakia (OR = 0.448; 95 % CI 0.255–0.787; p = 0.012) and, even more markedly, against carcinoma (OR = 0.281; 95 % CI 0.157–0.504; p < 0.001). No significant differences were detected between leukoplakia and control groups for the AA and AT genotypes (p > 0.05). Conclusions. The EGFR rs2227984 polymorphism is a significant genetic marker of susceptibility to HNSCC, whereas the T allele appears to confer protection against both malignant and premalignant oral conditions. Genotyping of A2073T may enhance early-screening strategies, enabling timely identification and personalised follow-up of high-risk individuals.