Colon Cancer Study Cites Link to Genetic Defects
In a discovery that could lead to better diagnosis and treatment of a common form of cancer, scientists have found that more than 20% of colon cancers arise from genetic defects that now have been traced to a specific chromosome.
The discovery, by an international team of researchers, is expected to lead to the development of diagnostic tests, a more accurate assessment of the potential of colon polyps to become malignant, and possibly a means of preventing the disease from developing in some people.
“I think it’s an exciting finding because it gives us a window on the origin of colon cancer--an area where we have been floundering around,” said Dr. John J. Mulvihill, chief of clinical genetics at the U. S. National Cancer Institute.
Findings Described
The research team, headed by Dr. Walter F. Bodmer of the Imperial Cancer Research Fund in London, reported its findings in two articles in this week’s issue of Nature, a British science journal.
The report is the latest addition to a list of cancers that have been found to have a genetic basis. They include neuroblastoma, an inherited form of eye cancer; Wilm’s tumor, a kidney cancer that strikes children, and acoustic neuroma, a tumor of the hearing nerve.
Colon cancer is by far the most common type of cancer for which researchers have been able to establish a genetic link. An estimated 145,000 new cases of colon and rectum cancer and 60,000 deaths--second only to lung cancer--will occur this year in the U.S., according to the American Cancer Society.
The scientists from Britain and Israel made their discoveries by tracking down a clue obtained from studying a patient who was mentally retarded.
The patient also had an inherited condition known as familial polyposis, in which a very large number of polyps that tend to become cancerous develop in the colon.
Retarded Patient Studied
Because mental retardation often can be traced to some kind of chromosome abnormality, the scientists speculated that they might be able to learn more about polyposis by studying a retarded patient who also had that inherited disorder. Chromosomes are the carriers of genetic information.
In a telephone interview, Bodmer said the fact that the patient’s retardation was related to a chromosomal defect turned out to be important because it meant that the chromosome defect was large enough to be visible under a microscope.
This, in turn, meant that the researchers were able to identify which of the 46 human chromosomes to focus on as they searched for the region that is responsible for polyposis.
They found that the defect consisted of a missing small piece of chromosome No. 5. In order to learn whether the defect had anything to do with colon cancer, they began looking at the genetic material in tumor cells removed from patients with the common kind of colon cancer that occurs in persons who do not have polyposis.
Using tools employed in genetic engineering to make the comparisons, they found that the genetic material from more than 20% of the colon cancers they examined lacked the same regions of the No. 5 chromosome that had been missing in the retarded patient with the inherited polyposis.
Linked to Tumors
This finding indicates that when that region is missing or defective, colon cancer appears to result. Noncancerous cells removed from those same patients had a normal complement of genetic material. Only the tumor cells showed the genetic change.
The scientists believe that colon cancer in such cases is triggered when mutations occur in colon cells during the normal process of cell division. It is well established that such mutations occur not infrequently in many cells of the body, but usually result in no damage because the genes located at those sites involve functions that are not vital.
The scientists theorize that in the case of colon cancer, the mutated genes had been involved in the regulation of tissue growth. When they no longer are present, cell growth becomes uncontrolled and cancer may occur.
Bodmer said that although the team was able to show this defect in only 20% of colon cancers, he believes that possibly 40% of all colon cancers are caused in this manner. Further, he said, more advanced techniques necessary to pinpoint very small changes among the millions of genes on each chromosome may someday show that even more colon cancer is due to this cause.
Useful Blood Test
In the meantime, Bodmer said, an immediate application of the work will be the development of a blood test that can identify individuals who have inherited the genetic defect that is responsible for polyposis, which occurs in between one in 5,000 and one in 10,000 persons.
Mulvihill, the U. S. geneticist, said the discovery may well result in the development within five years of a stool test to determine whether cells shed from the colon contain defective genetic material. Such a test, he said, could provide the earliest warning that a cancer has begun to grow and alert the person to seek immediate treatment.
The increase in fundamental knowledge that has been gained, Bodmer concluded, should also enable doctors to assess more accurately the malignant potential of colon polyps. And someday, he added, it may be possible to compensate for the defective genetic area with drugs that can replace the functions those genes normally perform.
