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

Document Type : Original Article


1 División de Medicina Molecular, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, México

2 Unidad de Investigación Seguimiento Enfermedades Metabólicas, Unidad Médica de Alta Especialidad Pediatría, Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco. México

3 División de Genética, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, México

4 Servicio de Oncología Médica, Hospital de Especialidades, Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, México

5 Servicio de Gastroenterología, Hospital de Especialidades, Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, México


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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