The Role of functional polymorphisms in oxidative stress-related genes on laryngeal squamous cell carcinoma

Abstract

Oxidative stress has a key role in laryngeal carcinogenesis as well as laryngeal squamous cell carcinoma (LSCC) progression [1]. One of the oxidative stress-related protein NFE2L2 mediate protection against oxidants itself and controls the expression of other antioxidant response elements–dependent genes [2]. Another gene involved in antioxidant protection, p21 also plays multiple functions in cell cycle arrest, apoptosis, and transcriptional regulation [3]. Higher p21 and NFE2L2 facilitate squamous cell carcinoma progression and metastasis [4, 5]. Genetic variation in oxidative stress-related genes may alter the coded protein level and impact the pathogenesis of LSCC. The present study investigated the association of functional single-nucleotide polymorphisms (SNP) in the p21 and NFE2L2 genes with LSCC clinicopathological features. The current study investigated the association of the fourth functional SNP in the NFE2L2 (rs10183914, rs35652124) and p21 (rs1801270, rs1059234) genes with the LSCC clinicopathological features. Genomic DNA and clinical data were collected from 261 Eastern European (Lithuanian) patients with LSCC. Genotyping of SNPs was performed using TaqMan Genotyping assays. The associations of polymorphisms with clinicopathologic variables primary tumor stage (T1 and T2/T3 and T4), lymph node status (positive/negative), distant metastasis status (positive/negative), and tumor grade (G1 and G2/G3) were evaluated by Pearson’s chi-square or Fishers’s exact test. All studied genotypes were in Hardy-Weinberg equilibrium and had the same distribution as the 1,000 Genomes project Phase 3 dataset for the European population. Evaluating the associations between studied polymorphisms and clinicopathological variables it was found, that carrying of T allele (TT+CT vs CC) in NFE2L2 rs35652124 was associated with positive lymph node status (Odds ratio (OR) 2.21; 95% confidence interval (CI) 1.03-6.74; p=0.041), positive distant metastasis status (OR 4.12; 95%CI 1.01-6.89; p=0.045) and high tumor grade (OR 3.65; 95%CI 2.10-7.32; p=0.034). Significant associations were found between p21 gene polymorphisms rs1059234 minor allele T carrying (TT+CT vs CC) and advanced tumor stage (OR 0.37; 95%CI 0.02-0.68; p=0.002). The study also shows that carrying of minor A allele (AA+CA vs CC) in another p21 gene polymorphism rs1801270 was associated with advanced tumor stage (OR 0.43; 95%CI 0.24-0.79; p=0.006). p21 polymorphism C allele (CC+CA vs AA) was associated with high cancer grade (OR 0.18; 95%CI 0.02-0.43; p=0.043). According to the present study, there is a correlation between polymorphisms in p21 and NFE2L2 genes and LSCC clinicopathological features. Functional SNPs in these genes may have the potential to operate as markers contributing to the assessment of LSCC clinical characteristics.