Association of MTHFR 677C>T and 1298A>C genetic polymorphisms with colorectal cancer: Genotype and haplotype analysis in a Southeast Iranian population

Abstract Background The methylenetetrahydrofolate reductase (MTHFR) gene is involved in DNA methylation, synthesis and repair, which influences the risk of cancers. Many studies have demonstrated that the MTHFR rs1801133 and rs1801131 polymorphisms are linked with the risks of colorectal cancer (CRC). However, no study has probed the relationship between these polymorphisms and CRC risk in southeast Iranian population. Therefore, the aim of this study was to investigate the association of these two polymorphisms with CRC risk in a case-control investigation. Methods A total of 200 confirmed CRC patients and 200 healthy controls (matched to sex and age) were recruited from the Southeast of Iran between 2014 and 2019. Genomic DNA was extracted and genotyped for the polymorphisms using the polymerase chain reaction-restriction fragment length polymorphism method. The relationship between the polymorphism and CRC risk was evaluated by logistical regression analysis. Results MTHFR 667C>T polymorphism was significantly associated with a lower risk of CRC (TT vs CC: p-value = 0.021; CT vs CC: p-value = 0.047; CT+TT vs CC: p-value = 0.017). The T-allele was associated with decreased risk for CRC (p-value = 0.012). However, we did not observe any association of 1298A>C with CRC. Furthermore, stratified analysis showed that MTHFR 667C>T polymorphism was correlated with tumor location in CRC patients. The frequency of T-A haplotype was significantly higher in the healthy controls compared to CRC patients (p-value = 0.021). Conclusion In conclusion, the T-allele of MTHFR 667C>T polymorphism was related to decreased susceptibility to CRC in this Iranian population. Moreover, the CT-AA and TT-AA combined genotypes and T-A haplotype of MTHFR 667C>T and 1298A>C polymorphisms were associated with decreased risk of CRC.