Adding to a rapidly emerging picture about colon cancer, an international team of scientists has discovered a second gene that causes what might be the most common of all inherited diseases.
People who carry the gene -- or another one identified late last year -- are born with almost certain odds of developing colon cancer. Together, the genes are believed to cause 90 percent of all cases of inherited colon cancer, a disease that strikes one out of 200 people in the United States.
The discovery, reported in this week's issue of Science, was made by researchers at the Johns Hopkins Oncology Center; Human Genome Sciences Inc. in Gaithersburg; the Institute for Genomic Research in Rockville; the University of Helsinki, Finland; and Creighton University in Omaha, Neb.
Dr. Kenneth Kinzler, one of the Hopkins researchers, said yesterday that the discoveries have led to a blood test that can be used to screen families that have been afflicted often by the disease.
The blood test searches for defective copies of the genes, identifying which family members are likely to get the disease and which ones are not.
So far, the Hopkins team has studied some 35 families in the Newfoundland, Finland, New Zeland and various parts of the United States.
In some families, the disease afflicts more than five or six family members within a few generations.
But so far, the test is being used on a limited basis -- and for research purposes only -- because it is too complicated to be applied more broadly. Dr. Kinzler said he hopes a more streamlined test will be developed in the next several years.
"Eventually, the test will involve providing a blood sample to your local physician, who will ship it off to a limited number of facilities that specialize in genetic analysis," Dr. Kinzler said.
Colon cancer is the fourth most common cancer -- trailing prostate, breast and lung cancer. Each year, about 156,000 new cases are diagnosed and 57,000 people die from the disease.
About one-sixth of the cases are inherited. An estimated 1 million people in the United States are born with the genetic predisposition and will develop colon cancer sometime in their lifetimes.
People identified as carriers would be advised to get annual colonoscopies, tests that often detect developing tumors. The cancer is frequently cured when it is caught early, making genetic screening a potential life-saver. "Genetic diagnosis combined with effective surveillance should reduce cancer deaths in these families by over 90 percent," said Dr. Bert Vogelstein, who directs the Hopkins laboratory.
The inherited disease looks and behaves like the nonhereditary cancer but tends to strike people much earlier in life -- sometimes in their 30s, 40s and 50s. The two genes -- called "mismatch repair genes" -- function in a similar manner.
Most people carry healthy copies, which prevent cancer by correcting genetic mistakes that occur when cells divide. But the defective gene allows mistakes to go uncorrected, and tumors to grow out of control.
The scientists also found two other genes that may be responsible for additional cases of inherited colon cancer because they function the same way. But scientists they have yet to find the proof -- the existence of defective versions in people who are sick with the illness.
Dr. Vogelstein said the first two genes are probably responsible for 90 percent of all cases while the second two may cause the remainder.
In screening family members, a laboratory would first take a blood sample from someone who is already sick and look for one of the four defective genes. "Each family has its own signature gene," he said. "All you need to do is test the genes in one affected member and find out which one of these four genes is the culprit. Then, you test other members for that gene."