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Close to 50 percent of U.S. cases result in death, and it is an insidious disease that lays waste to the quality of life of its victims and renders many permanently disfigured. Surgeries for internal cancers may leave scars, but most such scars can be covered by clothing. A face cannot be so easily masked; missing parts cannot be replaced. "You can lose your tongue and not be able to speak," says No-Hee Park, dean of the UCLA School of Dentistry, professor of oral biology and director of the Dental Research Institute at UCLA. "You can lose your jaw and not be able to chew. And even if you only lose part of your lips, it can look horrible." The ravaging effects of the disease are too often obvious. But Park's curiosity was piqued by the seeming conundrum of its causes. The medical community has long suspected that tobacco and alcohol play a part in the disease, but that influence is far from clear. "In general, if you don't smoke or drink, you don't have oral cancer," says Park. On the other hand, research shows that only a small number of the millions who smoke, let alone those who drink alcohol to excess, actually develop oral cancers. Funded by two four-year grants totaling $1.4 million from the National Institute of Dental Research, Park embarked on a search for the etiology of the disease. Researchers have long understood the carcinogenic properties of tobacco, especially the chemicals benzoapyrene and tobacco-specific nitrosamines found in tar. These chemicals, Park explains, damage DNA; the damaged material can eventually convert normal cells to tumor cells. But the chemicals are not carcinogenic by themselves. They must be activated by cell enzymes. Alcohol, it turns out, causes the cell to make more of the enzyme. Most of the harmful chemicals we ingest are cleared away by our liver—but chronic alcoholism can render the liver dysfunctional. |
Park's research showed, for the first time, that oral cancer often comes about as a result of a complex interaction of three factors: tobacco, alcohol and a third variable, human papillomaviruses (HPV). Park had initially studied the role of the herpes simplex virus in oral cancers, but following the discovery of HPV about 10 years ago, he became interested in the virus. Present in 40 to 50 percent of the population, HPV causes no damage in most people. Researchers, however, found that several of its 70 varieties were cancer-causing: HPV types 16 and 18, for example, were discovered in more than 90 percent of all cervical cancers. From this data, Park connected HPV to oral cancer. "Our mouth is structurally very similar to the vagina—it has the same type of epithelial [lining] cells," he explains. Indeed, 60 percent of oral cancers have now been linked to HPV. Park still needed to find the mechanism behind HPV-related oral cancers. Using a technique developed only about 10 years ago, he began to culture human epithelial cells and inject the DNA from HPV into the cells. Types 16 and 18, he found, made cells "immortalized," meaning they did not die after a normal life span. This is a major characteristic of cells that turn cancerous. More specifically, Park learned that proteins produced by the virus bind with the normal cells' P53 protein—the cell "guardian" that protects the body by either killing off damaged cells before they turn cancerous or by repairing their DNA. When P53 meets up with HPV, however, it loses its effectiveness as a guardian. Additionally, Park found that Hpv also activates oral cells' telomerase, whose function is negligible in most normal cells, but highly active in most cancer cells. Park also observed that ethanol—the alcohol we imbibe in beverages—inhibits the production of the valuable P53 protein, further diminishing the body's chances of repairing damaged cells. Hence, the link: Tobacco damages cell DNA; alcohol cuts down the number of DNA-repairing "guardian" cells; and HPV undermines many of the P53 cells that remain. Park's research may provide the basic information needed to find means of early detection of oral cancers. In turn, less invasive oral cancer treatments such as gene therapy may be developed. But the battle is far from over. "Cancer cells are very smart," Park says. "We have to outsmart them." —Michele Kort |
Mystery _________ The cause of cancer of the mouth are complex. The body itself plays a surprising role in the disease. |
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xcept in rare instances when someone famous like former Los Angeles Dodger Brett Butler is stricken, we almost never hear about cancers of the mouth. (In Butler's case, it was cancer of the tonsils, which ultimately forced him to retire from the game.) But the truth is, some 30,000 cases of oral cancer are reported annually in the U.S. And though it accounts for only 3 percent of all cancer in this country, it is the third most common cancer in the world.
