How folate metabolism affects colorectal cancer development and treatment; a story of heterogeneity and pleiotropy

摘要: Folate was identified as an essential micronutrient early in the twentieth century and anti-folate chemotherapy such 5-fluorouracil (5-FU) has been central to medical management of solid tumours including colorectal cancer for more than five decades. In intervening years, evidence gathered which shows that folate deficiency leads many human diseases throughout life-course. However, we still do not know all mechanisms behind functional deficiency, or indeed its rescue through supplementation with natural particularly synthetic folates. There is growing one adverse effect folic acid fortification programmes increased risk within populations. The complexity folate-dependent, one-carbon metabolism heterogeneity exists between individuals respect enzymes involved anabolic pathways, catabolism 5-FU, are explored this review. enzyme products some genes MTHFR exert multiple perhaps unrelated effects on phenotypes, development. We describe pleiotropy common genetic variants affect metabolism; discuss studies have investigated their potential predictive biomarkers.