If the results are applicable in humans, they could deepen our understanding of the synergistic interactions of this family of vitamins.
The researchers, led by Zhenhua Liu from Tufts University, studied the Wnt pathway - a cellular signalling pathway linked to more than 85 per cent of colon cancers - and found that mild depletion of all four B vitamins was needed to promote the risk of tumour formation.
Previously, studies have suggested that folate deficiency alone may promote the risk of colorectal cancer.
The new research suggests a more complex interaction.
However, 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.
"This emphasizes the concept that diets that are inadequate in multiple 1-carbon micronutrients may have important functional ramifications that do not exist with singlet or doublet states of depletion," wrote lead author Zhenhua Liu from Tufts University.
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.
Liu and collaborators used cancer-susceptible Apc mice to test if mild folate depletion alone or in combination with the other B-vitamins resulted in changes to the Wnt pathway.
They tested several biochemical, immunological and genetic markers over a ten-week dietary period, and found that a mild depletion of all four B-vitamins significantly increased the DNA damage localised at the Apc gene.
Folate depletion alone did not affect DNA.
The Apc (adenomatosis polyposis coli) gene is classified as a tumour suppressor.
Damage to the DNA that codes for this gene would therefore raise the risk of tumour formation.
"The findings, under conditions of relatively mild dietary deficiency, suggest that whereas mild folate deficiency alone may not be sufficient to observe an effect on Wnt signaling, the concomitant deficiency of folate and other B-vitamins may produce abnormalities of the type associated with human colorectal cancers," wrote the researchers.
At the end of October, researchers from universities in the UK and Ireland reported that riboflavin supplements increased the response to low-dose folate in colorectal cancer patients.
On the other hand, they noted that the combined supplements did not produce folate increases in the healthy people, suggesting benefits are limited to people with colorectal polyps.
( Cancer Epidemiology, Biomarkers & Prevention , Vol. 16, pp. 2128-2135)
The study was performed in collaboration with researchers from the University of Southern California, Harvard Medical School, and New England Medical Center.
It was funded by the National Institutes of Health (NIH), the USDA Agricultural Research Service, and the Cancer Research and Prevention Foundation.
Source: Journal of Nutrition Volume 137, Pages 2701-2708 "Mild depletion of dietary folate combined with other B-vitamins alters multiple components of the Wnt pathway in the mouse colon" Authors: Z. Liu, S.-W. Choi, J. Crott, M.K. Keyes, H. Jang, D.E. Smith, M. Kim, P.W. Laird, R. Bronson, and J.B. Mason.