METHYLENETETRAHYDROFOLATE REDUCTASE C677T POLYMORPHISM AND RISK OF COLORECTAL CANCER IN THE MACEDONIAN POPULATION
Matevska N1**, Josifovski T2**, Kapedanovska A1, Sterjev Z1, Serafimoska Z1, Panovski M2, Jankulovski N2, Petrusevska N3, Angelovska B3, Petrusevska G4, Suturkova L1, Dimovski AJ1*
*Corresponding Author: Aleksandar J. Dimovski, Ph.D., Center for Biomolecular Sciences, Faculty of Pharmacy, University Ss Cyril and Methodius, Skopje 1000, Republic of Macedonia; Tel.: +389- 2-3217 580; 3119 694; Fax: +389-2-3290 830; 3123 054; e-mail: adimovski@ff.ukim.edu.mk
page: 17
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Abstract

Methylenetetrahydrofolate reductase (MTHFR) regulates the flow of folate groups between DNA synthesis and DNA methylation. A common C677T substitution (Ala222Val) in exon 4 of the MTHFR gene has been linked with the risk of colorectal cancer (CRC). To assess this risk in the Macedonian population, we conducted a case-control study of 413 randomly selected CRC patients and 185 controls without a clinical diagnosis of CRC. We found a statistically significant inverse association between the MTHFR T allele (35.35% for the patients and 41.35% for the controls) and the CRC risk [odds ratio (OR) 0.776; 95% confidence interval (95% CI) 0.603-0.997; p = 0.047). The prevalence of the MTHFR T allele is lower in patients with advanced CRC (Duke’ s stage C and D) and with microsatellite instable tumors (MSI+), indicating the inverse association with the CRC aggressiveness and MSI status. This effect seems to be independent of gender, age of onset and localization. We concluded that the MTHFR 677T allele is more likely to have a protective effect on CRC development and progression in the Macedonian population.

      Key words: Methylenetetrahydrofolate reductase (MTHFR); C677T polymorphism; Colorectal cancer (CRC)

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1 Center for Biomolecular Sciences, Faculty of Pharmacy, University of Ss Cyril and Methodius, Skopje, Republic of Macedonia

2 Clinic for Abdominal Surgery, University of Ss Cyril and Methodius, Skopje, Republic of Macedonia

3 Institute of Radiotherapy and Oncology, University of Ss Cyril and Methodius, Skopje, Republic of Macedonia

4 Institute of Pathology, Faculty of Medicine, University Ss Cyril and Methodius, Skopje, Republic of Macedonia

 

 

 




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