Researchers in the United Kingdom and Texas combined proteomic and biochemical approaches to show that proteins known to play a part in formation of cancer are affected by low folate levels. Such a relationship was “hitherto unrecognised”, wrote the researchers in the Journal of Proteome Research.
Previous studies have already suggested that folate deficiency may promote the risk of colorectal cancer. The new study, led by Susan Duthie from the Rowett Research Institute in Aberdeen, deepens our understanding of this relationship.
The subject of folate and colorectal cancer is controversial, however, with some studies reporting that the B-vitamin may in fact increase the risk of the disease. On the other hand, other studies have reported protective benefits from folate for colorectal cancer.
Folate is found in foods such as green leafy vegetables, chick peas and lentils, and an overwhelming body of evidence has linked folate deficiency in early pregnancy to increased risk of neural tube defects (NTD) - most commonly spina bifida and anencephaly - in infants.
This connection led to the 1998 introduction of public health measures in the US and Canada, where all grain products are fortified with folic acid - the synthetic, bioavailable form of folate.
While preliminary evidence indicates that the measure is having an effect with a reported 15 to 50 per cent reduction in NTD incidence, parallel measures in European countries, including the UK and Ireland, are still on the table.
The Aberdeen-based researchers, in collaboration with scientists from the Incell Corporation in San Antonio, Texas, used functional biomarkers combined with proteomics to elucidate the mechanisms behind changes to DNA caused by folate deficiency in a human colon cells.
Proteomics is the study of proteins that carry out the biological functions in the biochemical pathway.
The cells were cultured in folate-deficient and folate-sufficient media, and proteins involved in proliferation, DNA repair, programmed cell death (apoptosis), and those linked to the transformation of cells into malignancies.
Proteins associated with all of these processes were altered, and the researchers specifically noted that proteins such as Nit2 and COMT associated with the malignant transformation had not previously been associated with low folate levels.
“This is the first study to describe how folate deficiency alters global protein expression and genomic stability in non-cancer-derived human colon cells in vitro,” wrote Duthie and co-workers.
“It is limited in that it investigates the effects of folate deficiency only in a single colon epithelial cell line, and protein expression was determined only at a single time point.
“Nonetheless, the principal aim of this initial study was to establish how severe folate deficiency altered DNA stability and global protein expression in the colon.”
Colorectal cancer accounts for nine per cent of new cancer cases every year worldwide. The highest incidence rates are in the developed world, while Asia and Africa have the lowest incidence rates.
Source: Journal of Proteome ResearchVolume 7, Pages 3254-3266, doi: 10.1021/pr700751y"The Response of Human Colonocytes to Folate Deficiency in Vitro: Functional and Proteomic Analyses"Authors: S.J. Duthie, Y. Mavrommatis, G. Rucklidge, M. Reid, G. Duncan, M.P. Moyer, L.P. Pirie, C.S. Bestwick