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ZINC DEFICIENCY LINKED TO INCREASED RISK OF LESS-COMMON FORM OF ESOPHAGEAL CANCER

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U.S. Department of Health and Human ServicesNATIONAL INSTITUTES OF HEALTHNIH NewsNational Cancer Institute (NCI)http://www.cancer.gov/EMBARGOED FOR RELEASETuesday, February 15, 20054:00 p.m. ETCONTACT:NCI Press Office301-496-6641ZINC DEFICIENCY LINKED TO INCREASED RISK OF LESS-COMMON FORM OF ESOPHAGEAL CANCERResearchers at the National Cancer Institute (NCI), part of the NationalInstitutes of Health, have found that zinc deficiency in humans isassociated with an increased risk of developing esophageal squamous cellcarcinoma, an often-fatal form of esophageal cancer that has about 7,000cases a year. NCI researchers used a novel approach to measure theconcentration of zinc and other elements directly in the esophageal tissue.Their results, appearing in the February 15, 2005, "Journal of the NationalCancer Institute"*, showed an inverse relationship between tissue zincconcentration and subsequent risk of esophageal squamous cell carcinoma.Dietary deficiency of zinc, an essential mineral, has been associated withesophageal cancer in rodents. So far, though, examining this association inhumans has been hampered by the difficulty of measuring zinc levels in thebody through traditional methods. "Measuring zinc levels in the blood is notvery sensitive," noted lead author Christian Abnet, Ph.D., of NCI's CancerPrevention Studies Branch. "Because zinc is maintained in a state ofequilibrium, just like body temperature, the readings will tend to besimilar. Calculating zinc from intake of meat and other dietary sourcesisn't very sensitive either since other compounds, like phytates in wholegrains, will inhibit zinc absorption."Abnet turned to a different technique: X-ray fluorescence spectroscopy,which involves bombarding a sample with high-intensity X-rays, causing theelements in the sample to fluoresce, or glow, with a characteristic energysignature. "This allowed us to measure element concentrations directly inthe tissue of interest," said Abnet, "so it should be the best indicator ofthe effects of zinc or other metals."Esophageal tissue samples were obtained from a population in Linzhou, China,that was followed from 1985 through 2001. People in this region are at highrisk for squamous esophageal cancer and tend to consume little meat and alot of whole grain, and therefore are more likely to be zinc deficient. Anearlier publication estimated that residents of this region get only 62 to72 percent of the U.S. dietary recommendations for zinc, whereas mostAmericans meet current dietary recommendation levels.A subset of the population underwent endoscopy with biopsy in 1985, and theNCI team, with the aid of Barry Lai, Ph.D., at Argonne NationalLaboratories, Argonne, Ill., examined these specimens. They measured zinc,copper, iron, nickel and sulfur levels in samples from 60 subjects whodeveloped esophageal squamous cell carcinoma during the 16 year follow-upand from 72 histology-matched subjects at the start of the study who did notdevelop the disease.The average tissue zinc concentration was significantly lower in subjectswho developed esophageal cancer than in control subjects (44 ng/cm2 comparedto 57 ng/cm2). When the researchers ranked the study participants byquartiles based on zinc concentration, they found that those in the highestquartile had a 5-fold lower risk of developing esophageal cancer than thosein the lowest quartile. Overall, 90 percent of subjects in the highestquartile were alive and cancer-free after 16 years, while only 65 percent ofthe subjects in the lowest quartile were alive and cancer-free. There wereno consistent associations with cancer risk for any of the other elementsstudied.These findings establish an initial connection between zinc and esophagealsquamous cell carcinoma in humans, although further research is needed toensure this association is more than a local phenomenon in an area ofextreme zinc deficiency. However, Abnet believes the technique itself holdsgreat promise for future element studies. "X-ray fluorescence spectroscopyhas many advantages," said Abnet. "You can apply it to most elements and youonly need a tiny tissue sample. Also, it doesn't damage the tissue, so youcan make multiple measurements on one sample." Abnet also noted that theysuccessfully measured samples collected and embedded in paraffin in 1985,demonstrating that other researchers could apply this technique to archivedtissue samples.For more information about cancer, please visit the NCI Web site athttp://www.cancer.gov or call NCI's Cancer Information Service at1-800-4-CANCER (1-800-422-6237).*Christian C. Abnet, Barry Lai, You-Lin Qiao, Stefan Vogt, Xian-Mao Luo,Philip R. , Zhi-Wei Dong, D. Mark, Sanford M. Dawsey. Zincconcentration in esophageal biopsy specimens measured by X-ray fluorescenceand esophageal cancer risk. "Journal of the National Cancer Institute",2005; February 16, 2005, 97(4).##This NIH News Release is available online at:http://www.nih.gov/news/pr/feb2005/nci-15a.htm.

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