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- <text id=93TT1687>
- <title>
- May 17, 1993: A Lethal Legacy
- </title>
- <history>
- TIME--The Weekly Newsmagazine--1993
- May 17, 1993 Anguish over Bosnia
- </history>
- <article>
- <source>Time Magazine</source>
- <hdr>
- MEDICINE, Page 51
- A Lethal Legacy
- </hdr>
- <body>
- <p>Scientists have discovered a renegade gene that causes colon
- cancer
- </p>
- <p>By CHRISTINE GORMAN--With reporting by J. Madeleine Nash/
- Chicago and Dick Thompson/Washington
- </p>
- <p> For almost a century, medical researchers have tried to
- figure out why colon cancer seems to run in certain families.
- Did their misfortune result from blind chance, a shared exposure
- to some cancer-causing trigger in the environment or their diet?
- Or could they have inherited a rogue gene that made them more
- susceptible to malignancy? Now a team led by scientists from
- Johns Hopkins University and the University of Helsinki believe
- that they have found the answer. "What has heretofore been
- called familial colon cancer can now be called heritable colon
- cancer," says Dr. Bert Vogelstein, professor of oncology at
- Johns Hopkins. "Our groups have proved beyond any shadow of a
- doubt that a genetically determined predisposition to colon
- cancer exists." About 1 in 7 cases of colon cancer--the second
- leading cause of cancer deaths in the world--can be attributed
- to this faulty gene.
- </p>
- <p> The newly discovered defect does not in itself produce
- cancer in the way that an inherited defect causes cystic
- fibrosis or sickle-cell anemia. "What the mutant gene does is
- create a predisposition to cancer," Vogelstein explains. "And
- it's only with additional mutations after birth that the cancer
- will appear."
- </p>
- <p> What is remarkable--and entirely novel--about the gene
- is that it may actively promote the accumulation of genetic
- errors, eventually causing a cell to become malignant. That was
- "a major surprise," says Albert de la Chapelle, chairman of the
- department of medical genetics at the University of Helsinki.
- "It doesn't work at all like we and others had thought." As
- reported in Science, the researchers estimate that 1 in 200
- people carries the defective gene. Of the 95% of them who will
- eventually develop cancer, 60% will get colon cancer and the
- rest will develop a variety of other malignancies, including
- tumors of the uterus, stomach, pancreas or urinary tract.
- </p>
- <p> In their attempt to locate the renegade gene, the
- scientists studied two families, one in North America and the
- other in New Zealand. In both cases, half of all adult family
- members had developed the disease. By comparing the DNA of the
- 40-odd family members who had tumors with the DNA of those who
- did not, the researchers hoped to detect a particular stretch
- of genes that could be linked to the disease. Such a unique
- pattern, called a genetic marker, would be a major step toward
- identifying the specific culprit gene. After discarding 344
- potential markers, the scientists finally found one that fit the
- bill.
- </p>
- <p> Even though the researchers have not yet isolated the
- gene, they suspect that it represents an entirely new pathway
- to peril. In the past, most genes linked to cancer, including
- a few linked to colon cancer, have been genes that play a role
- in regulating cell division, in some cases stopping cell growth
- when DNA is damaged. When such genes are themselves deranged,
- genetic errors can rapidly accumulate. But the newly discovered
- defect is not in a damage-control gene. Instead, it seems to be
- a direct agent of damage that somehow unleashes wave upon wave
- of DNA mutations over the course of a lifetime. As a result, a
- single inherited trait leads to "tens of thousands of
- alterations throughout the genome," Vogelstein marvels.
- </p>
- <p> This fundamental instability may help explain why patients
- suffering from hereditary colon cancer seem to respond better
- to treatment than those whose disease arises in other ways.
- Apparently their tumor cells are already so heavily damaged that
- the malignant tissue is actually more susceptible to
- chemotherapy and radiation than other types of cancer cells.
- </p>
- <p> Just as important, the marker may lead to better screening
- tests. Early detection makes all the difference to colon-cancer
- patients. About 90% of people whose tumors are found early are
- still alive five years after their diagnosis. That figure
- plummets to less than 10% once the cancer has spread beyond the
- intestines. However, according to a recent study, the most
- widely used screening test, which detects blood in stool
- samples, misses more than 70% of all tumors.
- </p>
- <p> Vogelstein expects that within three years there will be
- a better diagnostic test based on the newly discovered genetic
- defect. The first to benefit from such a blood test will be the
- 5 million to 10 million Americans who are now considered to be
- at an increased risk of colon cancer because of a strong family
- history (usually defined as having three or more relatives with
- the disease, one of them stricken before age 50). The test could
- cost $300 a family, according to Vogelstein. About three-fourths
- of family members will learn that they do not carry the gene.
- That does not means that they are immune to colon cancer, just
- that they bear an average risk (a 1-in-20 chance during their
- lifetime). The other 25% will probably undergo a colonoscopy,
- in which a fiber-optic scope is used to search for growths in
- the colon. The $1,000 procedure would then become an annual
- routine.
- </p>
- <p> Eventually, even people who have no family history of
- colon cancer could benefit from the current findings. Once all
- the genes whose damage can lead to intestinal tumors have been
- discovered, researchers may be able to detect such dangerous
- changes whenever they occur. "DNA testing as we know it now is
- not cost efficient," says Dr. Funmi Olopade, professor of
- oncology at the University of Chicago. "But the way technology
- is moving, 10 years from now this will no longer be such an
- exorbitant test to perform."
- </p>
-
- </body>
- </article>
- </text>
-
-