Too little folate in diet may raise colon cancer risk: mouse study
Last Updated: Thursday, November 2, 2006 | 10:02 AM ET
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A diet low in folic acid appears to increase the risk of colorectal cancer in laboratory mice and a similar deficiency could play a role in the human form of the disease, a study by Canadian researchers suggests.
In a one-year study of 137 mice, scientists at McGill University found that animals fed a diet deficient in folic acid — a B vitamin also known as folate — were more likely to develop colorectal cancer than rodents given a fully balanced diet that contained adequate folate.
"We found tumours in the mice that were on the low-folate diet and no tumours in mice that were on the regular diet," said geneticist Rima Rozen, scientific director of the Montreal Children's Hospital and the study's lead investigator.
Overall, one in four mice given low-folate diets developed intestinal tumours, with some of the animals developing more than one, said researchers, whose study was published Wednesday in the journal Cancer Research.
Rozen said several large human-population studies have suggested that low intake of folic acid, which is found in leafy green vegetables and citrus fruits, might be associated with an increased risk of colon cancer. But such studies cannot pinpoint with any accuracy what factor or factors definitely lead to a person developing a certain cancer.
Using mice allowed the researchers to carefully control possible contributing factors — including environment and diet, she said, bringing them closer to a direct cause and effect.
"What folate does, or the mechanism we propose in this study, is that lack of folate damages your DNA," Rozen said from Montreal.
Indeed, folic acid is vital to health: It is needed to help cells retain the integrity of DNA during division. Furthermore, it has been shown to help prevent certain types of heart disease and pregnant women who do not get enough risk producing offspring with neural tube defects such as spina bifida.
Rozen stressed that she's not suggesting people start loading up on folic acid. However, they should make sure to get the recommended daily allowance of 400 micrograms by eating foods such as broccoli, spinach and orange juice or by taking a multivitamin.
"I want to make sure people understand the value of recommended daily allowances," she said. "I don't want people to go out and take pharmacologic doses of anything. … In moderation, folate is important."
Double whammy
As part of the study, the researchers also tested mice with a genetic mutation that impairs the body's ability to metabolize folic acid. Rodents with the mutation that were also fed a low-folate diet had more than double the incidence of intestinal tumours.
"It's sort of a double whammy in the sense that it's not only the low dietary folate, but it's the combination," Rozen said, noting that 10 per cent of humans are believed to carry a similar genetic mutation.
Teasing out mechanisms
Dr. Andy Smith, a colorectal cancer surgeon at Sunnybrook Health Sciences Centre in Toronto, said the study is important because it appears to confirm the long-held suspicion that inadequate folic acid plays a role in tumour formation.
"It really helps tease out the actual mechanisms," Smith said.
And while one shouldn't jump to the conclusion that the mechanism found in mice is exactly the same in humans, he added, "in this case it really resonates because of the observations made so clearly in humans that low folate is associated with the development of tumours."
"Even if you have a healthy diet, you still ought to be talking to your physician about whether you should be having a test to screen for colorectal cancer," he said, recommending that Canadians aged 50 or older should have a fecal occult blood test or a colonoscopy.
"Because while your risk may be reduced, it's not eliminated. And people who live very healthy lives are still vulnerable to colorectal cancer."
By year's end, an estimated 20,000 Canadians will have been diagnosed with colorectal cancer. About 8,500 will die of the disease in 2006, making it the second most deadly cancer after lung cancer.
Dr. Sharlene Gill, a medical oncologist at the B.C. Cancer Agency, lauded the study for advancing medicine's understanding of folic acid's role in tumour prevention. But she noted that unlike the mice in the study, humans are exposed daily to many other factors that could contribute to colorectal cancer.
"So it's much more than just folate, but it's one part of the puzzle," Gill said from Vancouver. "This does support the idea that a balanced, healthy diet that does include an appropriate intake of fruits and vegetables may contribute to a lower incidence of cancer."
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