Genetic Variation in Glutamate Carboxypeptidase II and Interaction with Dietary Natural Vitamin C May Predict Risk for Adenomatous Polyp Occurrence

Background: The C1561T variant of the glutamate carboxypeptidase II (GCPII) gene is critical for naturalmethylfolylpolyglutamte (methylfolate) absorption, and has been associated with perturbations in folatemetabolism and disease susceptibility. However, little is known on C1561T-GCPII as a risk factor for colorectalcancer. Therefore, this study examined whether C1561T-GCPII influences folate metabolism and adenomatouspolyp occurrence. Materials and
Methods: 164 controls and 38 adenomatous polyp cases were analysed todetermine blood folate and plasma homocysteine (Hcy) level, dietary intake of natural methylfolate, syntheticpteroylglutamic acid (PteGlu), vitamin C and C1561T-GCPII genotype.
Results: In controls and cases, 7.3 and18.4 percent of subjects respectively, were found to have the CT genotype, increasing the risk for adenomatouspolyp occurrence 2.86 times (95% CI:1.37-8.0, p=0.035). Total dietary folate, methylfolate and PteGlu intakeand the level of erythrocyte folate and plasma Hcy did not predict the occurrence of an adenomatous polyp.However, dietary natural vitamin C intake was associated with adenomatous polyp risk within C1561T-GCPIICT genotype subjects (p=0.037).
Conclusions: The findings suggest that C1561T-GCPII variation may beassociated with risk for adenomatous polyp, and vitamin C may modify risk by interacting with the variantgene, its expression product and/or folate substrates.