As example a discovery/validation study conducted on 302 Caucasian Dukes’ stage B2 and C colon cancer patients homogeneously treated with 5-FU based regimen, demonstrated that a specific combination of MTHFR rs1801131 and TYMS 3’-UTR ins/del (rs16430) polymorphisms, instead the single locus, could represent a significant predictor of increased toxicity risk[83]. The gene discussed is TYMS; the disease is colonic neoplasm.