Teams of scientists at Johns Hopkins and several other research labs have isolated a gene responsible for a rare inherited form of colon cancer. On the way, they also found the suspected triggers for the more common forms of the disease. The discoveries, reported in the journals Science and Cell, illustrate the promise of progress to come in mapping out the human genome.
Several years ago, Bert Vogelstein of the Hopkins Oncology Center found a series of "tumor suppressor genes" that act like brakes, controlling cell growth. Deactivated or damaged, these genes can cause a cell to grow into a tumor. One, p53, when altered, can turn a benign tumor into a cancer. Now his lab says a malignant colon cell collects mutations in other genes as well, demonstrating that cancer is a multi-step process.
Working with teams led by Curt Harris of the National Cancer Institute, Ray White of the Howard Hughes Medical Institute at the University of Utah and the Tokyo Cancer Institute, Dr. Vogelstein's team has isolated the gene causing familial adenomatous polyposis (FAP). Inheriting a mutated version of this gene is a crucial first step in the conversion of a normal colon cell into a cancerous one, Dr. Vogelstein says. The same gene turned up in tumor cells from patients suffering more widespread forms of colon cancer, indicating that once damaged, it becomes a switch helping to activate all colon cancers.
One immediate result of this research is a blood test for the inherited defect, relieving members of families ravaged by FAP of the need to submit to uncomfortable colon examinations to check for disease. Cancerous or pre-cancerous conditions can be discovered early, when treatment is more effective. Even a fetus can be tested for the damaged gene, which could lead some couples to decide not to have a child.
That leads to ethical questions. The morality of screening the unborn for a disease which doesn't affect people until their late teens, a disease which can be treated if diagnosed early, is bound to be challenged. And if a parent's or a doctor's morality can be questioned, a medical insurer's use of the new test to determine whether to extend or to continue coverage would be fraught with controversy.
fTC Over the long-term, these discoveries could lead to better chemical treatments for cancer. Presenting doctors with a detailed blueprint of the workings of a disease which kills 60,000 Americans a year could result in a new family of pharmaceuticals to arrest pre-cancerous states, halt cancers at early stages and reduce cancers that are further advanced. For many families, the news from Hopkins gives them hope for a new beginning.