People with just one copy of the variant adenomatous polyposis coli (APC) gene do not have an increased risk of colon cancer. But people with two copies of the B1822V variant (meaning they inherited B1822V variants from both parents) have a much lower colon cancer risk if they eat a low-fat diet, according to the study.

The APC gene was discovered 10 years ago as a result of its association with colorectal cancer risk. Some APC mutations interfere with the gene?s normal functions. People who inherit an APC gene with such a mutation from one of their parents will have a condition known as familial adenomatous polyposis. These individuals develop hundreds of precancerous polyps during their teens or 20s. One or more of these polyps typically become cancerous before the patient reaches 40 years of age.

In contrast to these harmful APC mutations, the B1822V variant does not interfere with proper functioning of the APC gene and does not increase colorectal cancer risk. In fact, it may help the gene work even better than usual among individuals who eat a low-fat diet.

At this stage, the finding is an intriguing puzzle to researchers, according to two senior epidemiologists with the American Cancer Society (ACS).

In the study, a low-fat diet offered no protection against colon cancer for the general population, only for the small group with two copies of the B1822V variant, says Eric Jacobs, PhD, senior epidemiologist with the ACS? department of epidemiology and surveillance research.

Between 1991 and 1994, the researchers collected information on 1,585 colon cancer patients, then compared their genetic, dietary, and lifestyle factors. They found that, regardless of APC gene type, the risk of colon cancer decreased with:

• vigorous physical activity
• lower weight
• regular, low-dose use of aspirin or other nonsteroidal anti-inflammatory drugs

Those findings are nothing new. But in the 5% of the study group with the double-variant APC gene, a low-fat diet lowered the risk of colon cancer by about 80%. Only people with this double-gene variant reduced their colorectal cancer risk with a low-fat diet.

As the study authors noted, "these findings could be due to chance, and so they should be replicated in other populations," cautions Marji McCullough, PhD, also a senior epidemiologist with the ACS. "We're just at the tip of the iceberg looking at gene-diet interactions."

Senior author John D. Potter, PhD, head of the Cancer Prevention Program at Fred Hutchinson Cancer Research Center in Seattle, agrees. Is the low-fat diet and lowered cancer risk a cause-effect relationship? Or just a quirk in the data? "We don't know what to make of it," he says.

However, says Potter, the finding is "raising some interesting questions about the possible functioning of this gene."

Potter, McCullough, and Jacobs agree that the public is still well-advised to follow current ACS guidelines for lowering cancer risk: eat lots of fruits and vegetables. Eat less fat, particularly animal fat. Don't smoke. Don't drink alcohol excessively. Achieve and maintain an ideal weight. Exercise.

"Regardless of your genetic makeup, physical activity is good," Jacobs says, "and this is a conclusion seen in virtually every study of colon cancer."

Other recent evidence points to red meat consumption as an important factor, Potter says. Well-done meats appear to be part of the story, he says, as well as processed meats, such as sausage and lunch meat.

"There are other good reasons for eating a low-fat diet," Potter says, "mostly for its effect on obesity, cardiovascular disease and diabetes."