PMID- 34828284 OWN - NLM STAT- MEDLINE DCOM- 20220215 LR - 20220215 IS - 2073-4425 (Electronic) IS - 2073-4425 (Linking) VI - 12 IP - 11 DP - 2021 Oct 23 TI - Associations of Polymorphisms Localized in the 3'UTR Regions of the KRAS, NRAS, MAPK1 Genes with Laryngeal Squamous Cell Carcinoma. LID - 10.3390/genes12111679 [doi] LID - 1679 AB - 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. FAU - Insodaite, Ruta AU - Insodaite R AD - Institute of Biology Systems and Genetic Research, Lithuanian University of Health Sciences, 50103 Kaunas, Lithuania. FAU - Smalinskiene, Alina AU - Smalinskiene A AD - Institute of Biology Systems and Genetic Research, Lithuanian University of Health Sciences, 50103 Kaunas, Lithuania. FAU - Liutkevicius, Vykintas AU - Liutkevicius V AD - Department of Otorhinolaryngology, Lithuanian University of Health Sciences, 50161 Kaunas, Lithuania. FAU - Ulozas, Virgilijus AU - Ulozas V AD - Department of Otorhinolaryngology, Lithuanian University of Health Sciences, 50161 Kaunas, Lithuania. FAU - Poceviciute, Roberta AU - Poceviciute R AD - Institute of Biology Systems and Genetic Research, Lithuanian University of Health Sciences, 50103 Kaunas, Lithuania. FAU - Bielevicius, Arunas AU - Bielevicius A AD - Institute of Biology Systems and Genetic Research, Lithuanian University of Health Sciences, 50103 Kaunas, Lithuania. FAU - Kucinskas, Laimutis AU - Kucinskas L AD - Institute of Biology Systems and Genetic Research, Lithuanian University of Health Sciences, 50103 Kaunas, Lithuania. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20211023 PL - Switzerland TA - Genes (Basel) JT - Genes JID - 101551097 RN - 0 (3' Untranslated Regions) RN - 0 (KRAS protein, human) RN - 0 (Membrane Proteins) RN - EC 2.7.11.24 (MAPK1 protein, human) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1) RN - EC 3.6.1.- (GTP Phosphohydrolases) RN - EC 3.6.1.- (NRAS protein, human) RN - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras)) SB - IM MH - 3' Untranslated Regions MH - Aged MH - Case-Control Studies MH - GTP Phosphohydrolases/*genetics MH - Genetic Association Studies MH - Genetic Predisposition to Disease MH - Humans MH - Laryngeal Neoplasms/genetics/*pathology MH - Lithuania MH - Lymphatic Metastasis MH - Male MH - Membrane Proteins/*genetics MH - Middle Aged MH - Mitogen-Activated Protein Kinase 1/*genetics MH - Neoplasm Staging MH - *Polymorphism, Single Nucleotide MH - Proto-Oncogene Proteins p21(ras)/*genetics MH - Squamous Cell Carcinoma of Head and Neck/genetics/*pathology PMC - PMC8625477 OTO - NOTNLM OT - KRAS OT - MAPK1 OT - NRAS OT - laryngeal squamous cell carcinoma OT - mitogen-activated protein kinases OT - single-nucleotide polymorphisms COIS- The authors declare no conflict of interest. EDAT- 2021/11/28 06:00 MHDA- 2022/02/16 06:00 PMCR- 2021/10/23 CRDT- 2021/11/27 01:05 PHST- 2021/09/14 00:00 [received] PHST- 2021/10/18 00:00 [revised] PHST- 2021/10/21 00:00 [accepted] PHST- 2021/11/27 01:05 [entrez] PHST- 2021/11/28 06:00 [pubmed] PHST- 2022/02/16 06:00 [medline] PHST- 2021/10/23 00:00 [pmc-release] AID - genes12111679 [pii] AID - genes-12-01679 [pii] AID - 10.3390/genes12111679 [doi] PST - epublish SO - Genes (Basel). 2021 Oct 23;12(11):1679. doi: 10.3390/genes12111679.