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

RESULTS

The characteristics of the study participants are presented in Table 1. Allele and genotype frequencies of MTHFR C677T polymorphism are presented in Table 2. No significant deviations from Hardy-Weinberg equilibrium were noted in either group. We found a statistically significant inverse association between the MTHFR T allele (35.35% for CRC patients and 41.35% for controls) and CRC risk (OR 0.776; 95% CI 0.603-0.997; p = 0.047). Prevalence of the variant allele (677T) within this population did not differ significantly from the prevalences reported in other Caucasian populations (30-35%) [30,31].

      We observed a difference in overall genotype distribution between the CRC patients and controls (CC 42.61%; CT 44.07%; TT 13.32% for CRC patients and CC 35.13%; CT 47.03%; TT 17.84% for controls) even though it did not reach statistical significance (p = 0.064 TT; p = 0.185 CT; CC as reference). The MTHFR 677T allele was not associated with CRC either in a recessive (TT vs. CT + CC) or in a dominant (TT + CT vs. CC) model (OD 0.708; 95% CI 0.442-1.134; p = 0.149 and OD 0.729; 95% CI 0.729; p = 0.085 respectively), although there was a trend for significance towards the dominant model.

      We stratified the subjects according to gender, age, and tumor stage, localization and microsatellite instability (MSI) status. Table 3 provides the ORs for the association between these variables and CRC risk (in all calculations the C allele was used as a reference). The results point towards a protective role of the MTHFR T allele in the progression of CRC, as shown with the lower prevalence of the T allele in patients with aggressive CRC (OD 0.682; 95% CI 0.484-0.961; p = 0.028 for Duke’s C and OR 0.575; 95% CI 0.305-1.085; p = 0.084 for Duke’s D). Although with borderline significance, we found a similar inverse association between the MTHFR 677T allele and MSI status (OD 0.561; 95% CI 0.308-1.020; p = 0.055).



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