University of Minnesota News Service
6 Morrill Hall
100 Church St. S.E.
Minneapolis, MN 55455
November 26, 1984

GENETIC DISCOVERY LEADS TO CANCER TEST;
FOLIC ACID LINKED TO PREVENTION

The discovery of 51 weak points in human chromosomes is leading to a simple blood test for detecting susceptibility to cancer and shows how folic acid, a B vitamin, could lower the risk of developing cancer.

Jorge J. Yunis, a University of Minnesota geneticist who has pioneered new techniques of studying human chromosomes, reports the discovery of the 51 chromosome-gene weak points called "fragile sites" in the Dec. 7 issue of Science.

The weak points, which are found in all people, correspond to where chromosomes break in different types of cancer, including blood, lymph gland, ovarian and lung cancer.

Yunis reports that healthy cells of patients with different types of cancer showed a higher than normal weakness at the same chromosome-gene site where a break occurs in their tumor cells. "Such chromosomal weakness may make a healthy person more susceptible to cancer," he said in an interview.

Some families have a higher breakage rate in their chromosomes, which could explain why cancer is more frequent in them, Yunis said.

To confirm the association, he is conducting a two-year large-scale study of cancer patients, cancer-prone families and healthy people in the general population, he said.

Yunis's discovery also could have vast implications for preventing cancer. In his study, normal chromosomes showed the weak points when cells are deprived of folic acid or thymidine, essential substances for DNA synthesis.

Yunis found that chromosomes from healthy test subjects were made especially resistant to breakage after the subjects took a folic acid supplement.

Cells that lacked folic acid broke more easily when caffeine was added. Although caffeine by itself is not a carcinogen, it interferes with the normal repair process during DNA replication after cells have been damaged by a carcinogen or folic acid deficiency, Yunis writes.

Folic acid is a B-complex vitamin ordinarily obtained from food. Leafy vegetables, asparagus, whole grain breads and cereals, fruits and liver are notably high in folic acid. Caffeine and related substances are found in coffee, tea, chocolate and in a number of carbonated drinks and pain-killing drugs.

Some types of cancer have been associated with the use of drugs that reduce the level of folic acid in the blood, Yunis said. These drugs include alcohol, oral contraceptives and some anti-convulsants used by epileptics.

Caffeine has been linked to cancer of the pancreas and to fibrocystic breast disease in women, he said.

Confirmation of Yunis's results would make possible testing for individual predisposition to and early diagnosis of different types of cancer, he said, adding that preventive measures could be taken.

People found to be at high risk could be checked regularly for signs of a solid tumor so that it could be removed well before it advances to the point where treatment is difficult. "High-risk individuals could take folic acid pills and avoid ingesting large amounts of substances like caffeine t reduce chromosomal weakness and lower the risk of cancer." Yunis said.

Yunis's finding represents a major advance for understanding the general mechanism of how a normal cell begins to be transformed into a cancerous one. He reports that some cancer genes (oncogenes) already have been found at the chromosome weak points and suggests that many others will be identified in the future.

In the interview, Yunis said that folic acid or thymidine deficiency in individual cells together with assault from carcinogens in food or the environment care probably involved in producing most of the chromosome-gene changes seen in cancer. He said he has reproduced in the test tube some of the chromosome defects characteristic of cancer by using folic acid-deficient cells and either a chemical carcinogen or caffeine.

The Yunis test may prove to have other applications besides in cancer susceptibility. He said it can be used as a highly sensitive method to screen chemical and environmental agents to measure their cancer-causing potential to human cells.

Also, patients undergoing cancer therapy might benefit because the test can be used to show the relative sensitivity of tumor cells to different drugs and radiation, he said.

BACKGROUND:

Jorge J. Yunis, M.D., Ph.D., is a professor of laboratory medicine and pathology at the University of Minnesota Medical School and a trustee of the Leukemia Society of America. A self-taught geneticist, he is best known for developing a widely used high-resolution chromosome technique for the study of birth defects, mental retardation and cancer.

His studies often appear in the leading scientific and medical journals. In an article in Science (July 9, 1983) he reported that most malignant tumors have a chromosome-gene defect, and recently in the New England Journal of Medicine (Sept. 27, 1984) he reported that acute myelogenous leukemia, a common blood cancer, actually represents many separate diseases, each with a completely different prognosis. Yunis has found that cancers of the lymph gland and a few solid tumors also can be subdivided through chromosome analysis and that testing the chromosomes of cancer cells should soon become routine to determine more precisely how long patients can be expected to live and to select the best treatment possible.

Last year in the July 9 issue of Science, Yunis reported finding a correlation between patients with blood and lymph gland cancer and 16 chromosomal fragile sites found in certain families. Largely because of that report, the National Cancer Institute has launched a national research program to investigate the role of chromosome-gene weakness in cancer predisposition.

-UNS-