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

Jennings, Barbara and Willis, Gavin (2015) How folate metabolism affects colorectal cancer development and treatment; a story of heterogeneity and pleiotropy. Cancer Letters, 356 (2 Part A). pp. 224-230. ISSN 1872-7980

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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.

Item Type: Article
Uncontrolled Keywords: colorectal cancer,pharmacogenetics,folate metabolism
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Pure Connector
Date Deposited: 24 Mar 2015 16:10
Last Modified: 22 Apr 2020 00:00
URI: https://ueaeprints.uea.ac.uk/id/eprint/52851
DOI: 10.1016/j.canlet.2014.02.024

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