It is an unexpected location for an advance in cancer research. Nestled in a valley on the banks of the Ottawa River, the laboratory shares a 10-acre site with five nuclear reactors where scientists test equipment for power plants. It is here, at Chalk River Nuclear Laboratories (CRNL), that medical researchers have developed a way to detect individuals with unusual sensitivity to cancer-causing radiation.
The test method, still in its rough lab form, is just one in a number of recent developments in cancer-related genetic research. Though their application in mass screening programs to detect cancer-prone individuals may be years away, the prospect is sufficiently near to prompt some scientists to ask the difficult moral question: do people really want to know whether they are cancer-prone?
Medical science has long known that some forms of cancer appear frequently in certain families, indicating a genetic link, while others are caused by external agents—cigarette smoke, chemicals in the workplace or large doses of radiation. About 200 genetic disorders carry with them a predisposition to cancer, says Dr. David Hoar, a genetic researcher at the University of Toronto. But the interplay between the genetic structure of cells and cancer-causing agents has not been well understood. Just how genetic abnormalities lead
to a high risk of cancer, what types of cancer are linked to specific genetic disorders and how to detect cancer-prone individuals are the questions researchers have been probing throughout the 1970s. Some pieces of the very large puzzle are beginning to fall into place.
In Boston, researchers last month reported the discovery of a genetic abnormality linked to a specific type of kidney cancer in a family in which 10 members were affected over three generations. The noted New England Journal of Medicine described the finding as “the first example of a dominantly inherited chromosomal aberration that imposes a high risk of a specific cancer” and suggested it could be a step toward compiling a catalogue of “cancer genes” of man.
At the University of Toronto, Hoar’s work with families in which the incidence of cancer is high has led to a test method for determining unusual sensitivity to chemical agents, some of them known carcinogens. A summary of his findings is soon to be published in the Canadian Journal of Genetics and Cytology.
And at Chalk River, work by Dr. Malcolm Paterson, head of the CRNL team, with individuals who have cancer-re-
lated rare hereditary disorders has led to the development of the test method for detecting unusual sensitivity to cancer-causing radiation.
“Some of the most rapid advances in understanding of cancer are coming in the field of somatic (nonreproductive) cell research,” says Dr. Robert W. Miller, chief of clinical epidemiology of the U.S. National Cancer Institute (NCI), part of the Boston team. The NCI has also placed Paterson’s Chalk River team under a three-year, $400,000 contract to continue its work.
One theory, borne out by the research to date, is that certain genetic abnormalities reduce the ability of cells to repair damage from cancer-causing agents. The damage takes the form of breaks in the “spiral staircases” or sugar-phosphate backbone of DNA, the repository of genetic information in cells. The result, Paterson says, is that cells successfully repair damage, die or mutate, carrying altered genetic information which is passed on to subsequent generations of cells and may lead to the appearance of cancer.
Paterson’s work with cultured skin cells of persons with a rare hereditary disorder provides, he says, “one of the best pieces of evidence available for a causal relation between defective repair of DNA damage and predisposition to cancer.” The simplest conclusion, Paterson says, is that they lack a fully functional enzyme needed for repair.
Hoar’s work is also exploring the genetic factor and he is looking into a method to test an enzyme deficiency in blood samples. The test results can be available in as little as five days. Compared with the six weeks required for the Paterson test method, it seems a giant step toward mass screening.
But Hoar cautions against such a development. “Is it fair to tell somebody that they may develop cancer?” he asks. “The psychological effect could be tremendously deleterious.” The personal and family issues aside, what would industries, pension plans or insurance companies do with such information? “If we get into that business the insurance companies are really going to hit us hard.”
In the meantime, the $400,000 U.S. contract, together with funds from Atomic Energy of Canada Ltd., operator of CRNL, is also enabling the research team to investigate other hereditary disorders. The prognosis, Paterson confidently predicts, is for the successful detection of cancer-prone individuals and their protection from environmental agents that might trigger the cancer. Undoubtedly, with a quick test to determine unusual sensitivity to radiation among future employees, “the nuclear industry would be a direct beneficiary.” Barbara Robson
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