WASHINGTON -- Bert Vogelstein of Johns Hopkins Universityand two other researchers announced on Wednesday thediscovery of a new gene that triggers colorectal cancer at apress conference at the American Association for theAdvancement of Science here.
Because the gene apparently triggers mutations that lead tocancer, it may also be responsible for cancers of the uterus,stomach, ovary, small intestine, gall bladder, kidney and ureter.
"This development in three different laboratories, which havecome to the same and complementary conclusions, will have amajor impact on health all over the world," said DanielKoshland, editor of the AAAS journal, Science.
The gene very strongly predisposes people to cancer of thecolon by affecting genes that were already known to prime thedisease: APC, RAS, DCC and p53. "What has heretofore beencalled familial colon cancer is now heritable colon cancer,"Vogelstein said. "If someone has a mutant form of the gene, heor she will get this cancer."
Tagged HNPCC (hereditary non-polyposis colorectal cancer), thegene is carried by an estimated one out of 200 people, and maybe the most common genetic defect known. Ninety-five percentof those with the mutation develop the disease, translatingannually into 600,000 new cases worldwide -- more new casesin the West than any other cancer except for lung. The lifetimerisk for colon cancer of all types is about one in 20. Bycomparison, only one Caucasion in 2,500 carries the gene forcystic fibrosis, and one person in 5,000 carries the gene formuscular dystrophy.
About 75,000 Americans died of colon and rectal cancer in1989.
The researchers had simply been searching for another tumorsuppresser gene, and were surprised to find that instead theirquarry was expanding or contracting repetitive sequences inthe genes of the colon cancer cascade, in colon tumors. They donot know whether damage to these sequences is causal or amarker for damage elsewhere in the genes, said StephenThibodeau, director of the molecular genetics laboratory at theMayo Clinic in Rochester, Minn. But the general pattern led tothe hypothesis that the HNPCC gene codes for a defective DNAreplication factor.
Indeed, damage caused by the gene is not limited to genes forcolon cancer. Among carriers, "there are literally thousands ofchanges throughout the genome," Vogelstein said, and othercancers, including ovarian, uterine and kidney, run in afflictedfamilies.
Vogelstein and Albert de la Chapelle, chairman of thedepartment of medical science at the University of Helsinki,Sweden, mapped the gene to the 3 million base pair, p215region of chromosome 2. This, said Vogelstein, is close enoughfor development of blood tests.
Companies can now develop these and DNA tests to determinethe genetic status of the estimated 5 million to 10 millionmembers of carrier families so that those harboring the genecan be more closely watched, and the rest "can be spared thecostly colonoscopies that would have to be done on all themembers of such families."
Besides cases of familial cancers, the de la Chapelle/Vogelsteingroup found repetitive sequences in 13 percent of 46 sporadic(non-family-associated) colon cancers tested, suggesting thatthese, too, may have been hereditary, despite appearances tothe contrary.
An odd clinical finding among those with the HNPCC gene isthat cancers tended to occur in the front half of the colon.Survival rates were higher than for patients with sporadiccolon cancer.
Five-year survival for cancer of the colon is about 50 percent.
-- David C. Holzman Washington Editor
(c) 1997 American Health Consultants. All rights reserved.