April 25, 1995
Media Contact: John Cramer
Phone: (410) 955-1534

A cancer of the mouth and throat linked in middle-aged people to smoking, drinking or specific genetic mutations is more likely in the elderly to result from random genetic errors accumulated over a lifetime -- in plain language, aging itself -- according to results of a study at The Johns Hopkins Medical Institutions.

The Hopkins scientists report that squamous cell carcinoma in patients over age 75 "more commonly results from accumulated spontaneous mutations rather than through heavy exposure to known carcinogens, and less commonly involves mutation of the p53 gene." Mutation of the p53 gene, a tumor suppressor gene that normally helps to prevent the formation and growth of cancers, is the most common cancer-related genetic mutation. Many independent mutations in different genes are required for a cell to become a cancer cell.

Results published in the March 1995 issue of Archives of Otolaryngology -- Head and Neck Surgery suggest older people may develop cancer because they accumulate genetic mutations that usually occur only in people who have been exposed to carcinogens. The aging process itself may increase the tendency for certain older people to develop cancer, the researchers say.

In support of this view, the study found that older patients who develop cancers besides those in the head and neck were more likely than their younger counterparts to get skin and prostate cancers as well. Both of these cancers are commonly associated with old age. In contrast, when middle-aged people developed other cancers, they were more likely to have lung and colon cancers. These cancers are strongly associated with smoking, drinking and mutations in the p53 gene.

Hopkins scientists say the study's results have two implications for the treatment of patients in their 70s or older:

These patients and their physicians should be alert to the risk of squamous cell carcinoma, the most common type of head and neck cancer, even if the patients have been non-smokers and non-drinkers.

Many patients in their 70s, 80s and 90s who have not smoked or drunk heavily are strong enough to undergo standard cancer-fighting therapies used on younger patients. Major surgery was an integral part of the treatment for most of the older patient group.

"Although stopping smoking would prevent a large number of cases of head and neck cancer each year, this study indicates that a group of older patients would continue to develop the disease spontaneously," says Wayne M. Koch, M.D., the study's lead author and associate professor of otolaryngology. "We believe that aggressive standard therapy should still be considered for older patients. If they are in generally good health, they should get the same types of treatment as younger people."

Aggressive therapy can include major surgery and/or radiation, with treatment determined on an individual patient basis.

For the study, researchers analyzed the medical records of patients with a new onset of squamous cell carcinoma between 1988 and 1993. The study group included 81 patients who developed the carcinoma of the upper respiratory and digestive tracts after age 75. The control group included 102 patients who developed the carcinoma between age 40 and 70. Researchers analyzed the patients' exposure to tobacco and alcohol, family history of cancer, treatment and other factors. This data was a subset of patient data from a recently reported Hopkins study that uncovered the most conclusive molecular evidence to date linking cigarette smoking to cancer.

Cancer of the upper respiratory and digestive tracts accounts for about 5 percent of all cancer cases in the United States annually, or about 70,000 cases. Eighty percent of these are squamous cell carcinoma.

While mutation of the p53 gene is the most common known genetic mutation in head and neck cancer, it is suspected that eight to 10 different mutations in this gene are required to develop this disease, Koch says. The study offers support for the possible involvement of multiple tumor-suppressor genes, which requires further research.

Koch estimated it will be five to 10 years before scientists identify all the head and neck cancer-related genes and their mutations and "someday maybe tailor treatment according to the mutation of the genes."

Other researchers on the study include Himanshu Patel, M.D.; Joseph Brennan, M.D.; Jay O. Boyle, M.D., and David Sidransky, M.D.

-- JHMI --
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