SHMT1 gene and folate deficiency increase risk for colon cancer

Offering a likely insight into how such cancers develop in humans - Cornell University researchers report they have identified a gene that increases the risk for colon cancer in laboratory mice when the animals' diets are deficient in folate.

The new study, "Shmt1 Heterozygosity Impairs Folate-Dependent Thymidylate Synthesis Capacity and Modifies Risk of Apcmin-Mediated Intestinal Cancer Risk," published in the March issue of the peer-reviewed journal Cancer Research, provides evidence that a combination of folate deficiency and reduced expression of the SHMT1 gene, which is required for accurate DNA synthesis, boosts the risk of colon cancer in a mouse model. The study indicates that the SHMT1 gene may be a factor in itself, and also demonstrates how dietary folate, a B vitamin, may interact with an individual's genetic make-up to increase colon cancer risk.

"Nutrition and genetics work together to contribute to the creation of cancer cells and, based on the similarity of folate metabolism in mice and humans, it is likely that this gene is associated with human colon cancer," said Patrick Stover, professor in the Division of Nutritional Sciences and the senior author of the paper.

Colorectal cancer is the second leading cause of cancer-related deaths in the United States, claiming more than 50,000 lives each year.

"Molecular antecedents that promote development of sporadic colon cancer include DNA damage. Lack of critical nutrients increases rates of DNA damage. Therefore, lack of folate has the potential to induce this damage that ultimately results in transforming normal cells to cancer cells," said Stover.

Screening for colorectal cancer is recommended for all individuals over 50; however, close to 40 percent of the U.S. population in this age group does not take this precautionary method. Individuals who choose not to pursue colonoscopies may want to ensure their diets contain adequate amounts of folate, Stover said. The U.S. recommended daily allowance for folate is 400 micrograms per day. Foods that are rich in folate include many fruits and vegetables, grains, legumes, nuts and seeds.