Study Shows That Colon-Cancer Subtypes Are Linked to Different Dietary Risk Factors

SNOWBIRD, UTAH -- Molecular epidemiologists from Roswell Park Cancer Institute in Buffalo and the University at Buffalo have shown for the first time that colon cancers that develop along separate pathways respond differently to known dietary risk factors.

The knowledge could someday be used to develop individualized dietary interventions for specific subtypes of cancers.

"We used to think that eating cruciferous vegetables had a protective effect against all colon cancers, and that eating meat and beef were risk factors for all colon cancers," said Andrew N. Freedman, Ph.D., research fellow at Roswell Park affiliated with UB's Department of Social and Preventive Medicine and lead researcher on the study.

"Now we know that is not the case. We effectively have divided colon cancer into two diseases: those that are affected by eating cruciferous vegetables and those that are not, and those in which eating meat and beef is a risk factor and those in which it is not. The key now is to intervene along these pathways."

Results of the study were presented here today at the annual meeting of the Society for Epidemiologic Research.

The case-control study analyzed colon cancer cases based on the presence or absence of alterations in the p53 gene. Freedman said alterations of the p53 gene are important in almost all types of cancer and play a role in at least half of colorectal cancers.

Knowing that diet has an effect on the development of colon cancer, Freedman and colleagues sought to determine if malignancies that occur via p53-negative and p53-positive pathways differed in their relationship to dietary and other potential risk factors.

The researchers obtained dietary, medical-history and lifestyle data from 163 patients with colorectal cancer and 326 healthy controls. All tumors were analyzed for the presence of p53 alterations. About half of the cases were found to be p53 positive. Dietary histories from patients with both types of tumors then were compared with diets of controls to determine if there was a relationship with various dietary factors.

The researchers found that the two pathways to malignancy were affected differently.

Patients whose tumors exhibited p53 alterations ate fewer cruciferous vegetables than controls. "This indicates that people who eat cruciferous vegetables may still get colon cancer, but it likely won't be caused by alterations in the p53 gene," Freedman said.

The major members of this vegetable group are broccoli, cabbage, brussels sprouts, and cauliflower.

Tumors that developed independently of p53 alterations were associated with family history of colon cancer and meat and beef consumption, and were not affected by a diet rich in cruciferous vegetables.

He said these findings could eventually have clinical implications. "Examinations for colon cancer often reveal benign polyps that can become malignant. These polyps usually are removed as a precaution. In the future if such tissue is found to be p53 positive, a physician may suggest a certain diet as a preventive measure."

Freedman said his group will continue to study the effect of diet and other lifestyle factors on the genesis of colorectal tumors.

"Many gene alterations, in addition to those affecting p53, are known to play a role in colon cancer," Freedman noted. "We will be conducting the same dietary comparisons with several other genes, and we will also be studying the effect of smoking, alcohol consumption and aspirin use on these pathways."

Members of Freedman's research team were Arthur M. Michalek, Ph.D.; James R. Marshall, Ph.D.; Curtis J. Mettlin, Ph.D.; and Nicholas J. Petrelli, M.D., all of the UB Department of Social and Preventive Medicine and Roswell Park; John E. Asirwatham, M.D., and Sateesh Satchidanand, M.D of The Buffalo General Hospital; Jennifer D. Black , Ph.D., of Roswell Park, and Zuo-feng Zhang, of Memorial Sloan-Kettering Cancer Center, New York City.