MKK4 variants rs3826392 and rs3809728 are associated with susceptibility and clinicopathological features in colorectal cancer patients

Objective(s): The mitogen-activated protein kinase kinase 4 (MKK4) plays a key role in several processes like inflammation, apoptosis, and tumorigenesis. Several authors have proposed that genetic variations in these genes may alter their expression with subsequent cancer risk. This study aimed to e...

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Main Authors: Kimberly Martínez-Casillas, Anilú Margarita Saucedo-Sariñana, Patricio Barros-Núñez, Martha Patricia Gallegos Arreola, Tomas Daniel Pineda Razo, María Eugenia Marín-Contreras, Silvia Esperanza Flores-Martínez, Mónica Alejandra Rosales-Reynoso
Format: Article
Language:English
Published: Mashhad University of Medical Sciences 2021-08-01
Series:Iranian Journal of Basic Medical Sciences
Subjects:
Online Access:https://ijbms.mums.ac.ir/article_18466_c0e4a052275af6639aa289130d350391.pdf
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author Kimberly Martínez-Casillas
Anilú Margarita Saucedo-Sariñana
Patricio Barros-Núñez
Martha Patricia Gallegos Arreola
Tomas Daniel Pineda Razo
María Eugenia Marín-Contreras
Silvia Esperanza Flores-Martínez
Mónica Alejandra Rosales-Reynoso
author_facet Kimberly Martínez-Casillas
Anilú Margarita Saucedo-Sariñana
Patricio Barros-Núñez
Martha Patricia Gallegos Arreola
Tomas Daniel Pineda Razo
María Eugenia Marín-Contreras
Silvia Esperanza Flores-Martínez
Mónica Alejandra Rosales-Reynoso
author_sort Kimberly Martínez-Casillas
collection DOAJ
description Objective(s): The mitogen-activated protein kinase kinase 4 (MKK4) plays a key role in several processes like inflammation, apoptosis, and tumorigenesis. Several authors have proposed that genetic variations in these genes may alter their expression with subsequent cancer risk. This study aimed to examine the possible association of MKK4 rs3826392 and rs3809728 variants in Mexican patients with colorectal cancer (CRC). These variants were also compared with clinical features as sex, age, TNM stage, and tumor location.Materials and Methods: The study included genomic DNA from 218 control subjects and 250 patients. Genotyping of the MKK4 variants was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) procedure. Results: Individuals with A/T and T/T genotypes for the rs3809728 (-1044 A>T) variant showed a significantly increased risk for CRC (P=0.012 and 0.007, respectively); while individuals with the G/G genotype for the rs3826392 (-1304 T>G) variant showed a decreased risk for CRC (P=0.012). Genotypes of the MKK4 rs3809728 variant were also significantly related to colon localization and advanced TNM stage in CRC patients. T-T haplotype (rs3826392 and rs3809728) of the MKK4 gene was associated with risk in patients with CRC.Conclusion: The rs3826392 variant in the MKK4 gene could be a cancer protective factor, while the rs3809728 variant could be a risk factor. These variants play a significant role in CRC risk.
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spelling doaj.art-ad582631b4b1430b8e588fb7a25c02ef2022-12-21T20:15:45ZengMashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-38662008-38742021-08-012481033104010.22038/ijbms.2021.56874.1269018466MKK4 variants rs3826392 and rs3809728 are associated with susceptibility and clinicopathological features in colorectal cancer patientsKimberly Martínez-Casillas0Anilú Margarita Saucedo-Sariñana1Patricio Barros-Núñez2Martha Patricia Gallegos Arreola3Tomas Daniel Pineda Razo4María Eugenia Marín-Contreras5Silvia Esperanza Flores-Martínez6Mónica Alejandra Rosales-Reynoso7División de Medicina Molecular, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, MéxicoDivisión de Medicina Molecular, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, MéxicoUnidad de Investigación Seguimiento Enfermedades Metabólicas, Unidad Médica de Alta Especialidad Pediatría, Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco. MéxicoDivisión de Genética, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, MéxicoServicio de Oncología Médica, Hospital de Especialidades, Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, MéxicoServicio de Gastroenterología, Hospital de Especialidades, Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, MéxicoDivisión de Medicina Molecular, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, MéxicoDivisión de Medicina Molecular, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, MéxicoObjective(s): The mitogen-activated protein kinase kinase 4 (MKK4) plays a key role in several processes like inflammation, apoptosis, and tumorigenesis. Several authors have proposed that genetic variations in these genes may alter their expression with subsequent cancer risk. This study aimed to examine the possible association of MKK4 rs3826392 and rs3809728 variants in Mexican patients with colorectal cancer (CRC). These variants were also compared with clinical features as sex, age, TNM stage, and tumor location.Materials and Methods: The study included genomic DNA from 218 control subjects and 250 patients. Genotyping of the MKK4 variants was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) procedure. Results: Individuals with A/T and T/T genotypes for the rs3809728 (-1044 A>T) variant showed a significantly increased risk for CRC (P=0.012 and 0.007, respectively); while individuals with the G/G genotype for the rs3826392 (-1304 T>G) variant showed a decreased risk for CRC (P=0.012). Genotypes of the MKK4 rs3809728 variant were also significantly related to colon localization and advanced TNM stage in CRC patients. T-T haplotype (rs3826392 and rs3809728) of the MKK4 gene was associated with risk in patients with CRC.Conclusion: The rs3826392 variant in the MKK4 gene could be a cancer protective factor, while the rs3809728 variant could be a risk factor. These variants play a significant role in CRC risk.https://ijbms.mums.ac.ir/article_18466_c0e4a052275af6639aa289130d350391.pdfcolorectal cancerhaplotypesmkk4susceptibilityvariants
spellingShingle Kimberly Martínez-Casillas
Anilú Margarita Saucedo-Sariñana
Patricio Barros-Núñez
Martha Patricia Gallegos Arreola
Tomas Daniel Pineda Razo
María Eugenia Marín-Contreras
Silvia Esperanza Flores-Martínez
Mónica Alejandra Rosales-Reynoso
MKK4 variants rs3826392 and rs3809728 are associated with susceptibility and clinicopathological features in colorectal cancer patients
Iranian Journal of Basic Medical Sciences
colorectal cancer
haplotypes
mkk4
susceptibility
variants
title MKK4 variants rs3826392 and rs3809728 are associated with susceptibility and clinicopathological features in colorectal cancer patients
title_full MKK4 variants rs3826392 and rs3809728 are associated with susceptibility and clinicopathological features in colorectal cancer patients
title_fullStr MKK4 variants rs3826392 and rs3809728 are associated with susceptibility and clinicopathological features in colorectal cancer patients
title_full_unstemmed MKK4 variants rs3826392 and rs3809728 are associated with susceptibility and clinicopathological features in colorectal cancer patients
title_short MKK4 variants rs3826392 and rs3809728 are associated with susceptibility and clinicopathological features in colorectal cancer patients
title_sort mkk4 variants rs3826392 and rs3809728 are associated with susceptibility and clinicopathological features in colorectal cancer patients
topic colorectal cancer
haplotypes
mkk4
susceptibility
variants
url https://ijbms.mums.ac.ir/article_18466_c0e4a052275af6639aa289130d350391.pdf
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