Furthermore, we found that individuals with germline pathogenic variants in MLH1 and the CC genotype of A1298C (rs1801131) had a significantly reduced risk of developing CRC (39%) compared to the rest of the cohort, indicating that the underlying germline MMR variant is important when looking at the modifying effects of MTHFR polymorphisms. This evidence concerns the gene MTHFR and colorectal carcinoma.