Associations of Polymorphisms Localized in the 3′UTR Regions of the <i>KRAS</i>, <i>NRAS</i>, <i>MAPK1</i> Genes with Laryngeal Squamous Cell Carcinoma

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 sing...

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Main Authors: Ruta Insodaite, Alina Smalinskiene, Vykintas Liutkevicius, Virgilijus Ulozas, Roberta Poceviciute, Arunas Bielevicius, Laimutis Kucinskas
Format: Article
Language:English
Published: MDPI AG 2021-10-01
Series:Genes
Subjects:
Online Access:https://www.mdpi.com/2073-4425/12/11/1679
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author Ruta Insodaite
Alina Smalinskiene
Vykintas Liutkevicius
Virgilijus Ulozas
Roberta Poceviciute
Arunas Bielevicius
Laimutis Kucinskas
author_facet Ruta Insodaite
Alina Smalinskiene
Vykintas Liutkevicius
Virgilijus Ulozas
Roberta Poceviciute
Arunas Bielevicius
Laimutis Kucinskas
author_sort Ruta Insodaite
collection DOAJ
description 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 <i>KRAS</i>, <i>NRAS,</i> and <i>MAPK1</i> 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 <i>KRAS</i>, <i>NRAS,</i> and <i>MAPK1</i> 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 <i>NRAS</i> rs14804 major genotype CC. Significant associations of the studied SNPs with clinicopathologic variables were also observed between <i>NRAS</i> rs14804 minor T allele and advanced tumor stage and positive lymph node status. SNP of <i>MAPK1</i> rs9340 was associated with distant metastasis. Moreover, haplotype analysis of two <i>KRAS</i> 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 <i>NRAS</i> and <i>MAPK1</i> genes may contribute to the identifications of patients at higher risk of LSCC lymph node and distant metastasis development.
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spelling doaj.art-480076e31f594edbb19f08fad2adf2322023-11-22T23:27:11ZengMDPI AGGenes2073-44252021-10-011211167910.3390/genes12111679Associations of Polymorphisms Localized in the 3′UTR Regions of the <i>KRAS</i>, <i>NRAS</i>, <i>MAPK1</i> Genes with Laryngeal Squamous Cell CarcinomaRuta Insodaite0Alina Smalinskiene1Vykintas Liutkevicius2Virgilijus Ulozas3Roberta Poceviciute4Arunas Bielevicius5Laimutis Kucinskas6Institute of Biology Systems and Genetic Research, Lithuanian University of Health Sciences, 50103 Kaunas, LithuaniaInstitute of Biology Systems and Genetic Research, Lithuanian University of Health Sciences, 50103 Kaunas, LithuaniaDepartment of Otorhinolaryngology, Lithuanian University of Health Sciences, 50161 Kaunas, LithuaniaDepartment of Otorhinolaryngology, Lithuanian University of Health Sciences, 50161 Kaunas, LithuaniaInstitute of Biology Systems and Genetic Research, Lithuanian University of Health Sciences, 50103 Kaunas, LithuaniaInstitute of Biology Systems and Genetic Research, Lithuanian University of Health Sciences, 50103 Kaunas, LithuaniaInstitute of Biology Systems and Genetic Research, Lithuanian University of Health Sciences, 50103 Kaunas, LithuaniaBackground: 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 <i>KRAS</i>, <i>NRAS,</i> and <i>MAPK1</i> 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 <i>KRAS</i>, <i>NRAS,</i> and <i>MAPK1</i> 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 <i>NRAS</i> rs14804 major genotype CC. Significant associations of the studied SNPs with clinicopathologic variables were also observed between <i>NRAS</i> rs14804 minor T allele and advanced tumor stage and positive lymph node status. SNP of <i>MAPK1</i> rs9340 was associated with distant metastasis. Moreover, haplotype analysis of two <i>KRAS</i> 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 <i>NRAS</i> and <i>MAPK1</i> genes may contribute to the identifications of patients at higher risk of LSCC lymph node and distant metastasis development.https://www.mdpi.com/2073-4425/12/11/1679laryngeal squamous cell carcinomasingle-nucleotide polymorphismsmitogen-activated protein kinases<i>KRAS</i><i>NRAS</i><i>MAPK1</i>
spellingShingle Ruta Insodaite
Alina Smalinskiene
Vykintas Liutkevicius
Virgilijus Ulozas
Roberta Poceviciute
Arunas Bielevicius
Laimutis Kucinskas
Associations of Polymorphisms Localized in the 3′UTR Regions of the <i>KRAS</i>, <i>NRAS</i>, <i>MAPK1</i> Genes with Laryngeal Squamous Cell Carcinoma
Genes
laryngeal squamous cell carcinoma
single-nucleotide polymorphisms
mitogen-activated protein kinases
<i>KRAS</i>
<i>NRAS</i>
<i>MAPK1</i>
title Associations of Polymorphisms Localized in the 3′UTR Regions of the <i>KRAS</i>, <i>NRAS</i>, <i>MAPK1</i> Genes with Laryngeal Squamous Cell Carcinoma
title_full Associations of Polymorphisms Localized in the 3′UTR Regions of the <i>KRAS</i>, <i>NRAS</i>, <i>MAPK1</i> Genes with Laryngeal Squamous Cell Carcinoma
title_fullStr Associations of Polymorphisms Localized in the 3′UTR Regions of the <i>KRAS</i>, <i>NRAS</i>, <i>MAPK1</i> Genes with Laryngeal Squamous Cell Carcinoma
title_full_unstemmed Associations of Polymorphisms Localized in the 3′UTR Regions of the <i>KRAS</i>, <i>NRAS</i>, <i>MAPK1</i> Genes with Laryngeal Squamous Cell Carcinoma
title_short Associations of Polymorphisms Localized in the 3′UTR Regions of the <i>KRAS</i>, <i>NRAS</i>, <i>MAPK1</i> Genes with Laryngeal Squamous Cell Carcinoma
title_sort associations of polymorphisms localized in the 3 utr regions of the i kras i i nras i i mapk1 i genes with laryngeal squamous cell carcinoma
topic laryngeal squamous cell carcinoma
single-nucleotide polymorphisms
mitogen-activated protein kinases
<i>KRAS</i>
<i>NRAS</i>
<i>MAPK1</i>
url https://www.mdpi.com/2073-4425/12/11/1679
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