Zinc supplementation may help prevent oral and esophageal cancer

Zinc deficiency fosters the development of tumors of the upper aerodigestive tract (UADT) in rats by increasing the expression of cyclooxygenase (COX)-2, new study results suggest. However, zinc replenishment or treatment with COX-2 inhibitors reverses hyperplasia and may protect against cancer.

Zinc is a required cofactor for more than 300 mammalian enzymes and a component of nuclear transcription factors involved in cell proliferation, differentiation and apoptosis, explain lead researcher Dr. Louise Y. Y. Fong and colleagues at Thomas Jefferson University in Philadelphia. Zinc deficiency, fairly widespread throughout the world, has been implicated in the etiologies of UADT cancer in humans.Dr. Fong’s group examined COX-2 gene expression, cell proliferation, and apoptosis in rats that were zinc sufficient, rats fed a zinc-deficient diet, and rats that were zinc replenished. The results appear in the Journal of the National Cancer Institute for January 5th.Zinc deficiency led to focal hyperplastic lesions and the expression of COX-2 protein and mRNA in the esophagus and tongue up to 14.7-fold higher than in control conditions.Zinc replenishment reduced cell proliferation within hours, the authors report, with normalized COX-2 expression by 48 hours. Treatment with COX-2 inhibitors celecoxib and indomethacin also reduced COX-2 overexpression, but to a lesser extent, and led to reductions in cell proliferation and an increase in apoptosis.After treatment with the carcinogen 4-nitroquinoline 1 oxide (NQO) for 15 weeks, the incidence of lingual squamous cell carcinomas in zinc-deficient rats was 74% compared with 22% in controls (p = 0.015), of greater tumor multiplicity (13.1 versus 4.3, p = 0.018). NQO also led to esophageal tumors in 39% and forestomach tumors in 61% of zinc-deficient animals, versus none in the controlsMoreover, tumors induced by NQO in zinc-deficient rats stained strongly for COX-2.’Our data provide what we believe to be the first evidence that zinc-deficient causes substantial cell proliferation in the squamous epithelium of the UADT,’ Dr. Fong’s group notes, ‘thereby providing a fertile environment for the genetic events that culminate in the development of malignant lesions’ in an animal cancer model that mimics aspects of human UADT cancer.They suggest that zinc supplementation may help prevent UADT cancer in persons at high risk for the disease. Zinc combined with low doses of retinoids and selective COX-2 inhibitors may also be of use in reversing oral leukoplakia, with less toxicity than that associated with high doses of retinoids alone.(Source: J Natl Cancer Inst 2005;97:40-50: Reuters Health: Oncolink: January 2005.)