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Allele and Genotype Frequencies of the Polymorphic Methylenetetrahydrofolate Reductase and Colorectal Cancer among Jordanian Population

  • Yousef, Al-Motassem (Department of Biopharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, The University of Jordan) ;
  • Shomaf, Maha (Department of Pathology, Department of Biochemistry, Faculty of Medicine, The University of Jordan) ;
  • Berger, Sondra (Department of Pharmaceutical and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina) ;
  • Ababneh, Nidaa (Molecular Biology Research Lab, Department of Biochemistry, Faculty of Medicine, The University of Jordan) ;
  • Bobali, Yahya (Molecular Biology Research Lab, Department of Biochemistry, Faculty of Medicine, The University of Jordan) ;
  • Ali, Dema (Molecular Biology Research Lab, Department of Biochemistry, Faculty of Medicine, The University of Jordan) ;
  • Al-Hasan, Sara (Molecular Biology Research Lab, Department of Biochemistry, Faculty of Medicine, The University of Jordan) ;
  • Diab, Ola (Department of Biopharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, The University of Jordan) ;
  • Ismail, Said (Molecular Biology Research Lab, Department of Biochemistry, Faculty of Medicine, The University of Jordan)
  • Published : 2013.08.30

Abstract

Background: Methylenetetrahydrofolate reductase (MTHFR) is involved in DNA synthesis and repair. We here aimed to investigate two common polymorphisms, C677T and A1298C, with genotype and haplotype frequencies in colorectal cancer (CRC) cases among Jordanian. Materials and Methods: 131 CRC cases were studied for MTHFR C677T and A1298C polymorphisms, compared to 117 controls taken from the general population, employing the PCR-RFLP technique. Results: We found the frequency of the three different genotypes of MTHFR C677T among Jordanians to be CC: 61.7%, CT: 35.2%, and TT 3.1% among CRC cases and 50.9%, 38.8% and 10.3% among controls. Carriers of the TT genotype were less likely to have CRC (OR=0.25; 95%CI: 0.076-0.811; p=0.021) as compared to those with the CC genotype. Genotype analysis of MTHFR A12987C revealed AA: 38.9%, AC: 45%, and CC 16% among CRC cases and 37.4%, 50.4% and 12.2% among controls. There was no significant association between genetic polymorphism at this site and CRC. Haplotype analysis of MTHFR polymorphism at the two loci showed differential distribution of the TA haplotype (677T-1298A) between cases and controls. The TA haplotype was associated with a decreased risk for colorectal cancer (OR=0.6; 95% CI: 0.4-0.9, p=0.03). Conclusions: The genetic polymorphism of MTHFR at 677 and the TA haplotype may modulate the risk for CRC development among the Jordanian population. Our findings may reflect an importance of genes involved in folate metabolism in cancer risk.

Keywords

Genetic polymorphism;colorectal cancer;methylene tetrahydrofolate;genomic DNA

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