Genetic Analysis of the C677t and A1298c Mthfr Polymorphisms in a Cohort of Romanian Patients with Sporadic Colorectal Cancer

Background: One of the mutated genes associated with a lower level of 5MTHF necessary for DNA methylation and possibly implicated in the carcinogenesis of sporadic colorectal cancer (CRC) is the gene encoding the methylenetetrahydrofolate reductase enzyme (MTHFR). Objectives: to investigate the frequency of the C667T and A1298C MTHFR variants in patients with sporadic CRC and controls; to establish the relative risk for sporadic CRC in association with these two polymorphisms. Patients and methods: Genotyping of C677T and A1298C MTHFR polymorphisms using PCRRFLP methods was done in 69 patients diagnosed with CRC and referred from the Surgical Clinic III Cluj. Sixty seven individuals without any signs of malignancy formed the control group. Results: The CT677 and TT677 genotypes were greater in patients with sporadic CRC compared to controls (34.78% vs. 25.37%, OR 1.57; 95% CI [0.74-3.28], p=0.23 and 8.69% vs. 4.47%, OR 2.13; 95% CI [0.51-8.91], p=0.47, respectively). The 1298AC and CC1298 genotypes were associated with an OR of 1.63 (49.27% vs. 37.31%, 95% CI [0.82-3.23], p= 0.15) and 3.00 (4.34% vs. 1.49%, 95% CI [0.3-29.58], p=0.6) for sporadic CRC. Patients positive for C677T and A1298C polymorphisms have a higher frequency of colon cancer in the left side than in the right side (18.84% vs. 4.34%, OR 5.11, 95%CI [1.38-18.83], p< 0.01, and 23.18% vs. 10.14%, OR 2.67, 95%CI [1.02-6.98], p=0.03, respectively). Moreover, patients positive for C677T and A1298C polymorphisms have a higher frequency of colon cancer than rectal cancer (34.78% vs. 18.84%, OR 2.3, 95%CI [1.05-5.01], p= 0.03, and 28.98% vs. 15.94%, OR 2.15, 95%CI [0.94-4.92], p= 0.06, respectively). Conclusions: Our study confirms the relationship between MTHFR genotypes and sporadic colorectal cancer. High risk individuals could benefit from effective prevention and treatment with 5FU strategies in order to reduce the mortality of sporadic colorectal cancer.