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Title: First Molecular Evidence Linking Cigarette Smoke to Lung Cancer
URL: http://www.pslgroup.com/dg/D016.htm
Doctor's Guide
October 17, 1996


DUARTE, Calif., Oct. 17, 1996 -- Researchers at the Beckman Research Institute at City of Hope Thursday reported the first molecular evidence linking a specific compound in cigarette smoke directly to lung cancer.

The study, Preferential Formation of Benzo(a)pyrene Adducts at Lung Cancer Mutational Hotspots in p53, appears in the Oct. 18 edition of the journal Science.

Since the release in 1964 of the first U.S. Surgeon General's report linking cigarette smoking to lung cancer, researchers have reported overwhelming statistical evidence that smoking causes lung cancer. Also, scientists have identified numerous possible carcinogens in the "tar" of cigarette smoke. However, researches had not yet determined which specific carcinogen, or combination of carcinogens, participate in the development of lung cancer.

The City of Hope study, conducted by Gerd P. Pfeifer and Mikhail F. Denissenko, in conjunction with Annie Pao and Moon-shong Tang of M.D. Anderson Cancer Center, University of Texas, suggests that a benzo(a)pyrene-metabolite in the "tar" or a structurally related compound, is directly involved in the transformation of human lung tissue.

The study provides a direct etiological link between a defined cigarette-smoke carcinogen and human cancer, the authors note.

Using a sophisticated genetic amplification technique developed at City of Hope, researchers analyzed the damage to specific sites in the p53 tumor suppressor gene by benzo(a)pyrene, which is known to bind to DNA and to be associated with the initiation of cancer in model systems.

The researchers found that the gene damage by benzo(a)pyrene matches exactly with several mutational hot spots specific to lung cancer, indicating that the tissue is systematically damaged by the cigarette smoke carcinogen.

"Dr. Pfeifer's elegant study, part of the emerging field of molecular epidemiology, permitted the positive identification of the specific molecule associated with the development of lung cancer. Such technology will permit more reliable classification of the cancer potential of environmental toxins than has been possible in the past. Such knowledge has the potential to save literally billions of dollars by eliminating unnecessary environmental protection regulation of harmless agents and intensifying control of known carcinogens," said Dr. John Kovach, executive vice president medical and scientific affairs at City of Hope.

Lung cancer is currently the leading cause of cancer deaths in the United States and is also the most common type of tumor worldwide. More than 419,000 Americans died of lung cancer last year, according to the American Cancer Society, which estimates that smokers lose an average of 15 years of life.

Founded in 1913, City of Hope is one of the world's leading research and treatment centers for cancer and other life-threatening diseases, including diabetes. The largest provider of bone marrow transplantation services in California, City of Hope is a National Cancer Institute-designated Clinical Cancer Research Center.

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