Background: Genetic variations, localized in the 3' untranslated region (UTR) in mitogen-activated protein kinase (MAPK) pathway-related genes, may alter the transcription and impact the pathogenesis of laryngeal squamous cell carcinoma (LSCC). The present study investigated the associations of single-nucleotide polymorphisms (SNP), localized in the 3'UTR) of the KRAS, NRAS, and MAPK1 genes with LSCC risk and clinicopathological features.
Methods: Genomic DNA and clinical data were collected from 327 adult men with LSCC. The control group was formed from 333 healthy men. Genotyping of the SNPs was performed using TaqMan SNP genotyping assays. Five KRAS, NRAS, and MAPK1 polymorphisms were analyzed. All studied genotypes were in Hardy-Weinberg equilibrium and had the same allele distribution as the 1000 Genomes project Phase 3 dataset for the European population.
Results: Significant associations of the studied SNPs with reduced LSCC risk were observed between NRAS rs14804 major genotype CC. Significant associations of the studied SNPs with clinicopathologic variables were also observed between NRAS rs14804 minor T allele and advanced tumor stage and positive lymph node status. SNP of MAPK1 rs9340 was associated with distant metastasis. Moreover, haplotype analysis of two KRAS SNPs rs712 and rs7973450 revealed that TG haplotype was associated with positive lymph node status in LSCC patients.
Conclusions: According to the present study, 3'UTR SNP in the NRAS and MAPK1 genes may contribute to the identifications of patients at higher risk of LSCC lymph node and distant metastasis development.
Keywords: KRAS; MAPK1; NRAS; laryngeal squamous cell carcinoma; mitogen-activated protein kinases; single-nucleotide polymorphisms.