Folate-Deficient Mice Prone to Colorectal Cancer

November 3, 2006

MONTREAL, Nov. 3 -- For the first time, researchers have shown directly that a deficiency in folate can lead to colorectal cancer -- at least in mice.

MONTREAL, Nov. 3 -- A deficiency in folate can lead to colorectal cancer, at least in mice, researchers have shown for the first time.

Previously, population studies have hinted that people eating a high-folate diet have a 30% to 40% reduced risk of colorectal cancer compared with people with a low-folate diet, according to Rima Rozen, Ph.D., of the McGill University Health Center.

Now, in an animal model that mimics sporadic colorectal cancer development in humans, which includes up to 85% of all such cancers, Dr. Rozen and colleagues have shown that mice on a low-folate diet had significantly greater risk of cancer than those eating a normal diet, they reported in the Nov. 1 issue of Cancer Research.

"This research, which is consistent with previous epidemiological studies in humans, demonstrates a clear link between low dietary folate and the initiation of colorectal cancer in animal models," Dr. Rozen said. "None of the mice fed a control diet developed tumors whereas one in four mice on the folate-deficient diet developed at least one tumor."

The study also provided insight into the mechanism by which folate deficiency leads to disease, Dr. Rozen said -- a finding that could lead to novel therapies.

In humans, a common genetic variant leads to a deficiency of the enzyme methylenetetrahydrofolate reductase (MTHFR), Dr. Rozen and colleagues said, which plays a key role in metabolizing folate and is associated with colorectal cancer and other neoplasias when dietary folate is low.

For this study, the researchers used mice with a germ-line mutation that makes them susceptible to colorectal cancer, but with an additional wrinkle. Some of the mice also had a defective allele in the gene for MTHFR, which created a deficiency in the enzyme, the researchers said.

After a year, the researchers found that none of the animals on the control diet (including 26 with the MTHFR deficiency) had developed tumors, while 20 of the 80 mice fed a low-folate diet (including 64 with the MTHFR deficiency) had intestinal cancers. The difference was statistically significant at P