Discovery of Genetic Defect Will Aid Colon Cancer Detection
Researchers have discovered a new kind of genetic defect that doubles a person’s risk of colon cancer and is present in one of every 17 American Jews, making it the most common cancer-associated mutation ever identified in any ethnic population.
The mutation, apparently rare in non-Jews, appears to be responsible for about one in four cases of inherited colon cancer in Ashkenazi Jews--those of Eastern European ancestry, who constitute more than 95% of this country’s 6 million Jewish people. It can be detected with a newly available $200 blood test, which some geneticists predicted would quickly become one of the more commonly used genetic tests.
Doctors called the discovery a major advance since a positive blood test can alert people to the need for regular colon examinations, called colonoscopies, which can detect colon cancer in its earliest stages. The disease is easily prevented or cured when growths in the colon are spotted early and removed.
“This is perhaps the best example yet of a situation where a genetic test will not only detect a significant number of folks at increased risk, but in a circumstance where you have something to offer them in the way of an intervention,” said Francis Collins, chief of the National Human Genome Research Institute.
At the same time, experts expressed concern that federal protections against genetic discrimination still are not fully in place, even as the number and value of genetic tests grow. Several said they hoped the discovery would spur the passage of legislation, recently endorsed by President Clinton, to protect people against the misuse of genetic information by health insurers and others.
“Despite the potential benefits of this testing . . . there still are substantial risks for people, including insurance discrimination and the likelihood of adverse psychological effects for the individual or family members,” said Caryn Lerman, director of cancer genetics at Georgetown University’s Lombardi Cancer Center. “For an individual to make an informed decision and weigh the risks and benefits adequately, informed consent and pretest genetic counseling would have to be offered.”
The new work, led by Bert Vogelstein of the Howard Hughes Medical Institute at Johns Hopkins University in Baltimore, focused on a stretch of DNA called the APC gene. Scientists have known since 1991 that mutations in that gene can lead to colon cancer. The new work shows that a less dramatic kind of genetic variation in the APC gene, called a polymorphism, also predisposes to cancer--not by directly causing tumor formation but by making the gene unstable and prone to further damage by carcinogens.
Researchers said the identification of the new kind of cancer-promoting glitch could help them find the underlying causes of other kinds of cancers in different populations.
“We always assumed polymorphisms are harmless variations,” Vogelstein said, like spellings of the word “color” and “colour” in America and England. “Now people are going to be going back and looking at all these to see what else they may be doing.”
The new research, which appears in the September issue of Nature Genetics, involved genetic analyses of blood or tissue samples taken from about 1,000 Ashkenazi Jews. It concluded that Ashkenazim who carry a genetic polymorphism called 11307K in either of their two APC genes (one inherited from each parent) have a 16% to 30% chance of getting colon cancer during their lifetime--double the odds of other Ashkenazim.
Most colon cancers are due to genetic changes acquired during a person’s lifetime, but an estimated 15% to 50% are caused by inherited genetic alterations--most of them still undiscovered.
The new alteration may account for about one-quarter of those in the Jewish population. The high number is probably due to the mutation’s presence in the group’s early ancestors and the relative lack of intermarriage.
Diets high in fiber and low in fat lower a person’s risk of getting colon cancer, which is the third most common type of cancer in U.S. men and women and will kill about 55,000 Americans this year. Doctors recommend periodic colonoscopies starting at age 50 to watch for the development of precancerous growths called polyps, which can turn into tumors. But many people avoid the painful hour-long procedure, which involves threading a long viewing device up the large intestine.
“Colonoscopies are not pleasant. You can easily convince yourself, ‘I’m healthy. Don’t worry about me,’ ” Vogelstein said. With the new blood test, however, people who test positive may find themselves motivated to sign up for the potentially lifesaving procedure.
Collins agreed that the blood test may benefit many people. But the approximately 1,200 genetic counselors in this country are already overtaxed, he said, and a recent study in the New England Journal of Medicine found that other health professionals such as doctors do not have the training to provide adequate counseling.
“How will this information be explained to people so they understand that in the low likelihood of a positive test, there is still an 88% chance they will not get colon cancer?” Collins asked.
“Error No. 2 is when the test comes back negative and you think, ‘There’s one kind of cancer I never have to think about,’ and when recommendations come down for colonoscopies at age 50 you think, ‘I can skip it.’ ” That ignores the fact that most colon cancers, even in Ashkenazim, are from causes other than the newly identified defect, Collins said.
