Brothers’ Research Casts New Light on Colon Cancer Risks
Seven years ago, Cedric Garland and his brother Frank were looking at a U.S. county-by-county map showing the death rate from different types of cancers and became intrigued by the large white splotches across the Southwest for colon cancer and the large dark splotches in the Northeast.
The white indicated low colon cancer mortality, and the dark high mortality for data covering the period between 1950 and 1969. The two San Diego epidemiologists, then at Johns Hopkins University in Baltimore, theorized that perhaps the amount of sunlight--with its vitamin D--played a role, since solar radiation tends to be far more intense in the Southwest.
To test their theory, the Garlands obtained federal dietary data that ruled out significant differences between geographic areas in terms of fruit, vegetable or fiber consumption--foods thought to reduce the risk of colon cancer. They then examined statistics worldwide--including five years of death certificates for Marrakech, Morocco--on the edge of the Sahara Desert--that showed colon cancer was almost non-existent in areas of intense sunlight nearer the Equator.
Their hypothesis, first published in 1980, suggested that dietary vitamin D as well as that obtained naturally from sunlight could lower the risk of colon cancer. It was further strengthened early this year when the Garlands and others completed a study of 20-year medical records of almost 2,000 Chicago men that showed those eating foods rich in vitamin D and calcium had a colon cancer rate one-third that of those who rarely ate such foods.
Last month, the first laboratory evidence indicating that an enriched calcium diet can lower the risk of colon cancer was issued by the Memorial Sloan-Kettering Cancer Center in New York. Colon cancer is the second most common type of cancer in the United States.
The linkage of colon cancer rates to sunlight, vitamin D and dietary calcium illustrates the path that medical research often takes, beginning with a large-population hypothesis that links diet or environment to disease, and ending ultimately with a tightly-controlled clinical study that tracks down a precise biological explanation. An ongoing UC San Diego Medical School study of more than 2,500 adults in Rancho Bernardo, now in its 16th year, is among those that have been yielding valuable information on the links between diet, smoking and disease.
“The first clues often come from large groups,” said Cedric Garland, today an assistant professor of community medicine at the UCSD Medical School and one of the researchers on the Rancho Bernardo study. “The key is to think in creative ways.”
And Garland said that in certain cases developing from population studies, such as with calcium and colon cancer, application of possible benefits should not necessarily await clinical verification.
“We’re trying to prevent disease,” Garland said. “And when we have a low-risk intervention that looks effective (calcium supplements), I see no reason to wait for laboratory confirmation.” Garland suggests that even President Reagan, who underwent successful colon surgery last summer to eradicate a cancer, should be on a vitamin D and calcium supplement, such as milk, to reduce risk of a second occurrence.
In the case of tobacco, the link between smoking and lung cancer was observed many years ago somewhat intuitively, similar to the way the Garlands first postulated the vitamin D and colon cancer connection in 1980. Population studies followed that showed lung cancers occurred with much higher frequency in persons who smoke.
While researchers have now determined the precise biological mechanism that causes cells to become cancerous, Garland said that anti-smoking campaigns did not need to wait for such studies.
In a similar pattern, Garland, after the brothers’ initial article on colon cancer was published, cast about for a large population study group. While he could eventually have obtained the necessary data from Rancho Bernardo or other large-population studies ongoing in Europe, Garland was able to short-circuit the process by using statistics already gathered from a Chicago study.
The head of UCSD’s Rancho Bernardo study, Dr. Elizabeth Barrett-Connor, knew of a Western Electric study in Chicago that had tested 2,000 workers for dietary habits between 1957 and 1959 and then followed them for the next 20 years to see what types of cancers developed. Garland and Barrett-Connor discovered that the 49 men who had come down with colon cancer had a significantly lower dietary intake of vitamin D and calcium than other men.
Garland expressed excitement at the Sloan-Kettering lab study announced Nov. 29 because such clinical work usually occurs many years after patterns suggested from population studies. Sloan-Kettering researchers gave calcium tablets to 10 people who had family histories of colon cancer. The tablets appeared to reverse potentially dangerous changes in the lining of the colon that often precede cancer, the researchers reported.
“There are going to be a proliferation of calcium studies, both clinical and epidemiological, as a result of the latest announcement,” Garland said. Rancho Bernardo participants will also be looked at for evidence of lower colon cancer rates, he said.
Garland praised the originators of the Chicago study for asking for such detailed dietary information over a 28-day period in 1957 and repeating the questions one year later. Researchers then watched for diseases that develop over a period of years and attempted to trace back the differences in diet or life style that could account for a greater or lesser occurrence of the diseases. Similar planning at the study’s beginning to ensure a high degree of follow-up has enabled Barrett-Connor and her colleagues to harvest a wealth of material from Rancho Bernardo.
“Ideally, you would want to measure changes every day but our studies are limited by the bounds of intrusiveness and money,” said Garland, who has authored numerous papers from out of the Rancho Bernardo data. “But realistically, you ask enough questions at the outset so that you can build a study to look at multiple outcomes.” Since the study first began in 1972, follow-up questions have been asked every two years and blood pressure and blood checks taken.
The original study, under sponsorship of the National Heart, Lung and Blood Institute, looked at the level of cholesterol and danger of heart disease. Subsequent studies by UCSD have found that nonsmoking women exposed to cigarette smoke of husbands have an elevated risk for heart disease, and that women who drink four or more cups of coffee a day had higher blood cholesterol levels and therefore may be at higher risk for heart disease. Further population and clinical research based on Rancho Bernardo findings are under way at present.
While the emphasis up until now has been on circulatory and heart-related diseases, data expected this year will begin to look at rates of cancer and link them to dietary habits. Garland hopes to add more evidence to the calcium and colon cancer link.
“Heart disease is the most common cause of death and you can get more adequate data (from population-based studies) earlier than for cancer, since cancers are a lot rarer and of many different kinds,” Garland said.
Garland pointed out that in many cases, such as smoking, certain hypotheses can only be tested through large-population studies. “Clinical testing is difficult, for example, in that you can’t stick a person in a room for 20 years and have them smoke, unless they want to.”
Garland said that population studies do not cause people intentional harm but simply measure the effects of their own choices; “we allow them to live their lives.”
But Garland added, “People can then act on the basis of what we find. For example, for coffee, if someone is naturally at higher risk for heart disease because of high cholesterol, then they should cut down their coffee consumption.
“I hope that our studies can equate longer life with better life.”
