The findings, published in the March issue of Cancer Epidemiology, Biomarkers and Prevention, join a small but growing body of evidence that dietary and behavioral changes can reduce the risk of some cancers in people who may have an inherited tendency to develop them.
“Previous research has demonstrated that people’s risk of developing colon cancer is two times greater if they have a parent or sibling who has been diagnosed with the disease,” says study leader Charles Fuchs, MD, of Dana-Farber. “Our study points to steps that such individuals can take to substantially lower those odds.”
With approximately 135,000 new cases reported each year, colon cancer is the third most commonly diagnosed cancer in the United States, and it is one of the leading causes of cancer-related deaths. Studies have shown that a variety of diet and behavioral modifications – such as stopping smoking, eating a diet high in fruits and vegetables, avoiding heavy red meat consumption, and having regular colon exams after age 50 – can reduce colon cancer risk in the general population. In the new study, Fuchs and his colleagues asked whether any of these measures are especially effective in people with a family history of the disease.
For answers, the researchers turned to the Nurses’ Health Study, a project which has been tracking the health of 121,700 female registered nurses in the United States for more than 25 years. The study, run by researchers at BWH, maintains an extensive databank of participants’ dietary and lifestyle habits, making it possible to explore the relation between people’s behavior and their risk of developing certain diseases.
Fuchs, who is also on staff at BWH and an assistant professor of medicine at Harvard Medical School, analyzed information from 88,758 nurses whose family health histories and dietary habits were recorded in the database. He focused on behaviors known to be associated with colon cancer to see if any were particularly helpful or harmful in people with a family history of the disease.
He found three: A diet high in folic acid, high in methionine (an essential amino acid), and low in alcohol intake, when followed at least five years, reduced colon cancer risk much more sharply in those with first-degree relatives who had the disease than in those without such a family history. Although all the study participants were women, Fuchs contends there’s no reason to think the results do not apply to men as well.
Participants with a family history of colorectal cancer who consumed low-folate diets were 2.5 times more likely to develop colon cancer than similar individuals who did not have a family history. In contrast, among participants on a high-folate diet, those with a family pattern of colorectal cancer did not experience any significant increase in colon cancer risk compared to those without such a pattern. “It appeared that either a high-folate diet or use of folate-containing multivitamins virtually eliminated the excess risk of colon cancer associated with a family history of the disease,” Fuchs explains.
While folic acid is found in fruits and vegetables and products made with enriched flour, obtaining the high levels tracked in the study – 400 micrograms a day – can be easily achieved by taking a multivitamin, Fuchs says. The quantity of alcohol consumption that appeared to increase the risk associated with a family history was greater than two glasses of wine per day.
The findings around methionine are more complicated. While high levels of the nutrient were shown to reduce the influence of a family history of colorectal cancer on the development of the disease, high amounts also may be associated with the “hardening of the arteries” that can lead to heart attacks. As a result, dieticians do not recommend taking methionine supplements.
The new study not only provides guidance to people with family risks of colon cancer, Fuchs comments, but also may point toward a better understanding of the biology of the disease. Scientists know that folic acid, methionine, and alcohol all affect a process known as “methylation,” in which specialized compounds of hydrogen and carbon are attached to various structures and products of cells.
Methylation plays a vital role, for example, in creating the building blocks of DNA within cells. Without sufficient methylation, the DNA structure may become unstable, raising the prospect of certain diseases, including cancer.
It’s possible, Fuchs says, that families with a pattern of colon cancer may have some modest alteration in either DNA processing or repair that makes them particularly susceptible to deficiencies in the methylation process.
“This research may make it possible to identify genes that confer a greater risk of the disease in families with a history of it,” Fuchs remarks. “That would be an important step toward therapies able to reduce that risk. Our findings involving folate may offer a first clue.”
Co-authors of the study are Walter Willett, MD, Graham Colditz, MD, David Hunter, MD, Meir Stampfer, MD, Frank Speizer, MD, and Edward Giovannucci, MD, all of the Channing Laboratory at BWH, Harvard Medical School and Harvard School of Public Health.
The research was supported by the National Cancer Institute.
Dana-Farber Cancer Institute (www.danafarber.org) is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute.