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

Cancer letters (2014-03-13)
Barbara Anne Jennings, Gavin Willis
ABSTRACT

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

MATERIALS
Product Number
Brand
Product Description

Supelco
Folic acid, Pharmaceutical Secondary Standard; Certified Reference Material
USP
Folic acid, United States Pharmacopeia (USP) Reference Standard
Folic acid, European Pharmacopoeia (EP) Reference Standard
Supelco
Folic acid, analytical standard
Sigma-Aldrich
Folic acid, ≥97%
Sigma-Aldrich
Folic acid, BioReagent, suitable for cell culture, suitable for insect cell culture, suitable for plant cell culture, ≥97%
Sigma-Aldrich
Folic acid, meets USP testing specifications
Sigma-Aldrich
Capecitabine, ≥98% (HPLC)
Capecitabine, European Pharmacopoeia (EP) Reference Standard