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Jefferson scientists find zinc may help prevent esophageal, oral cancers

10.01.2005


Cancer researchers at Jefferson Medical College and the Kimmel Cancer Center at Thomas Jefferson University in Philadelphia have found that zinc treatment may help prevent esophageal and oral cancers in those individuals at high risk.



Oral and esophageal cancers are associated with nutritional zinc deficiency, and a rise in the expression of the enzyme COX-2 is connected with these cancers. Louise Fong, Ph.D., assistant professor of microbiology and immunology at Jefferson Medical College of Thomas Jefferson University, and her co-workers have found that zinc given orally to zinc-deficient rats reverses the development of precancerous conditions in the esophagus and tongue and reverses the high expression of COX-2 there as well.

These findings suggest that zinc supplements may prevent the development of esophageal or oral cancers, particularly in developing countries where zinc deficiency is a problem. The researchers reported their findings January 5, 2005 in the Journal of the National Cancer Institute. Zinc in the diet comes mostly from red meat and seafood. Whereas up to 10 percent of Americans have a zinc-deficient diet, as many as 2 billion individuals in developing countries are zinc-deficient. Epidemiological evidence show the incidence of esophageal and oral cancers is rising in recent years. As many as 13,000 Americans die from esophageal cancer each year.


Dr. Fong has been studying zinc deficiency and its connection to esophageal cancer for some 20 years, and has developed animal models of zinc deficiency and cancer susceptibility. Zinc deficiency, she says, increases cell proliferation in the esophagus and in the tongue, making both areas susceptible to carcinogens and increasing the risk of cancer development. In 2002, Dr. Fong reported that rats given a carcinogen while on a zinc-deficient diet developed esophageal cancer. Giving zinc prevented the cancer.

Dr. Fong wanted to know if zinc could regulate COX-2 expression in esophageal and tongue cancers. She and her co-workers compared COX-2 protein and gene expression in esophageal and tongue tissue in normal rats, zinc-deficient rats and in zinc-deficient rats that had received zinc. They found COX-2 expression was increased 10-to-15-fold in zinc-deficient rats. Cellular proliferation was similarly increased. After giving zinc to the deficient rats, COX-2 expression was markedly reduced and the precancerous cellular proliferation was reversed. The rats lacking dietary zinc were also treated with COX-2 inhibitors, celecoxib (Celebrex) and indomethacin. They found that the rats treated with the COX-2 inhibitors had a reduction in both COX-2 and cellular proliferation in the esophagus.

"Zinc treatment restores many systems affected by the lack of zinc," Dr. Fong notes. "Zinc deficiency upregulates COX-2. Zinc replenishment restores it to near normal levels." In the future, she and her co-workers would like to determine whether zinc in combination with low amounts of celecoxib can prevent upper aerodigestive tract cancers, including esophageal and oral cancers.

Steve Benowitz | EurekAlert!
Further information:
http://www.jefferson.edu

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