A nationwide study that may link nutrients found in carrots, oranges and other common foods with inhibiting the growth of potentially cancerous colon polyps is endangered because local investigators are having difficulty finding qualified subjects.
The object of the study, funded by a five-year, $3.5-million grant from the National Cancer Institute, is to learn whether patients who have recently had a polyp removed can be prevented from growing new polyps if they are given carefully measured doses of beta carotene and vitamins C and E. UCLA is one of six clinical centers around the country participating in the study, which is being coordinated by Dartmouth College.
"If this works out, we think it could be recommended to people at high risk of developing polyps," said Robert W. C. Haile, an epidemiologist at the UCLA Cancer Center and principal investigator in the local branch of the study.
Greater Interest Possible
He said it would be of particular benefit to persons who have already had a polyp removed, because there is about a 50% chance that they will grow another polyp within two years. Haile hopes that the recent removal of a cancerous polyp from President Reagan's colon will translate into greater interest in the study.
Beta carotene, a substance that the body converts into Vitamin A, has long been thought to have anti-cancerous properties. Vitamin C has been championed as a possible anti-cancer agent for more than a decade, most prominently by two-time Nobel Prize-winner Linus Pauling, whose theories have been vigorously rejected by other scientists. Less has been written about the role of Vitamin E in stopping cancer, but it, along with Vitamin C, is thought to block the formation of n-nitroso, a substance that has been carcinogenic in experimental settings.
The current study is seeking more than 700 subjects in the next two years. Since April, UCLA has enrolled only six persons toward its goal of 150 subjects. Also involved in the study are the Mayo Clinic, the University of Iowa and the Leahy Clinic, a cancer clinic in Burlington, Mass. Cornell University, while still technically part of the program, will drop out in September due to lack of recruitment, Haile said.
Haile said that a continued low recruitment rate could result in the elimination of funding for the program in Los Angeles, and could possibly threaten the national program. Robert Greenberg, an associate professor at Dartmouth Medical School and principal investigator of the national study, said recruitment "hasn't been easy anywhere." He added, however, that of the remaining clinics, UCLA and one other, which he declined to identify, were having the greatest difficulty in finding subjects.
Patients at the UCLA Medical Center and the Wadsworth and Sepulveda Veterans Administration hospitals were originally targeted for the study. Haile said that all the patients who were qualified had agreed to participate.
The problem, he explained, is that the eligibility criteria disqualify most prospective candidates. To participate in the current study, one must have had a polyp removed within the last three months and be in generally good health.
Other exclusionary criteria are any ongoing cancer, a history of invasive cancer of the large bowel or known polyps that remain in the bowel, a history of kidney stones, diabetes that requires urine testing for glucose, persons undergoing anti-coagulation therapy and women of child-bearing potential (age 18 through menopause).
Haile said the study is important because it is the first clinical trial of the link between polyps and the nutrients. Following initial experimental studies that dealt with animals and tissue cultures, later research centered on human observational studies where dietary questionnaires and blood samples were compared with incidences of polyps and colon cancer, Haile said.
Cancer and Diet Linked
The study attempts to build upon observational research showing that industrialized nations such as the United States, where the population consumes a substantial amount of animal fat, protein and refined carbohydrates, generally have a higher incidence of colon cancer than countries in Africa or South America, where diets tend to be high in vegetables and fiber and low in meat.
In past studies, colon cancer patients were questioned about their dietary history. Their diets were compared to that of a control group of persons who had never had cancer.
Although these studies have implicated fats, "there is quite a bit of inconsistency in the findings," Greenberg said.
In some studies, the groups of persons who had never had cancer tended to eat more vegetables, particularly those containing beta carotene. However, "the evidence is very far from convincing," and less consistent than it is in implicating fats, Greenberg said.
Polyps Can Be a Danger
A substantial proportion of colon cancers are thought to arise from polyps. Although only a small proportion of polyps become cancerous, it is thought that the longer they stay in the body, the more likely they are to become cancerous.
Harvard Medical School is conducting a massive study to determine the cancer-fighting ability of beta carotene. Half of the 27,000 doctors involved in the Physicians' Health Study are taking beta carotene capsules every other day. The other half is receiving a placebo. At the end of five years, the incidences of cancer in the two groups will be compared. Haile said results of the study will be available in several years.
Beta carotene is most often found in dark green and dark yellow vegetables and deep-yellow fruits, including broccoli, carrots, sweet potatoes, kale, turnip greens, dark-leaf lettuce, deep orange winter squashes and yams, apricots, nectarines, cantaloupe and peaches.
The body converts beta carotene to Vitamin A as needed. For this reason, beta carotene is not toxic while large doses of Vitamin A are, Haile said.
Vitamin C Debated
The debate over the cancer-fighting ability of Vitamin C dates to 1974, when Dr. Ewan Cameron, a Scottish surgeon, published a report claiming that high daily doses could cause tumors to regress in some cancer patients.
Two years later, a report by Pauling and Cameron compared the survival times of 100 terminal cancer patients who had received Vitamin C with 1,000 similar patients who had not. The patients receiving Vitamin C lived 210 days after being diagnosed as incurable; the others lived an average of 50 days.
Two studies conducted by researchers at the Mayo Clinic Cancer Center in Rochester, Minn., have failed to replicate these findings, however.
Vitamin E is thought to inhibit "free radicals," a species of molecule that can destroy healthy tissue. It is also thought to help conserve the body's supply of Vitamin A by preventing its oxidation in the intestinal tract, Haile said.
Haile said the project is now concentrating on the greater Los Angeles area. Patients or physicians interested in participating in the study may call (213) 825-5777.