MKK۴ variants rs۳۸۲۶۳۹۲ and rs۳۸۰۹۷۲۸ are associated with susceptibility and clinicopathological features in colorectal cancer patients

Objective(s): The mitogen-activated protein kinase kinase ۴ (MKK۴) 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 MKK۴ rs۳۸۲۶۳۹۲ and rs۳۸۰۹۷۲۸ 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 ۲۱۸ control subjects and ۲۵۰ patients. Genotyping of the MKK۴ 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 rs۳۸۰۹۷۲۸ (-۱۰۴۴ A>T) variant showed a significantly increased risk for CRC (P=۰.۰۱۲ and ۰.۰۰۷, respectively); while individuals with the G/G genotype for the rs۳۸۲۶۳۹۲ (-۱۳۰۴ T>G) variant showed a decreased risk for CRC (P=۰.۰۱۲). Genotypes of the MKK۴ rs۳۸۰۹۷۲۸ variant were also significantly related to colon localization and advanced TNM stage in CRC patients. T-T haplotype (rs۳۸۲۶۳۹۲ and rs۳۸۰۹۷۲۸) of the MKK۴ gene was associated with risk in patients with CRC.Conclusion: The rs۳۸۲۶۳۹۲ variant in the MKK۴ gene could be a cancer protective factor, while the rs۳۸۰۹۷۲۸ variant could be a risk factor. These variants play a significant role in CRC risk.

Keywords:

Colorectal cancer , Haplotypes , MKK۴ , Susceptibility , Variants