Zinc Deficiency Linked to Increased Risk of LessCommon Form of Esophageal Cancer
Researchers at the National Cancer Institute (NCI), part of the
National Institutes of Health, have found that zinc deficiency
in humans is associated with an increased risk of developing esophageal
squamous cell carcinoma, an often-fatal form of esophageal cancer
that has about 7,000 cases a year. NCI researchers used a novel
approach to measure the concentration of zinc and other elements
directly in the esophageal tissue. Their results, appearing in
the February 15, 2005, Journal of the National Cancer Institute*,
showed an inverse relationship between tissue zinc concentration
and subsequent risk of esophageal squamous cell carcinoma.
Dietary deficiency of zinc, an essential mineral, has been associated
with esophageal cancer in rodents. So far, though, examining this
association in humans has been hampered by the difficulty of measuring
zinc levels in the body through traditional methods. “Measuring
zinc levels in the blood is not very sensitive,” noted lead
author Christian Abnet, Ph.D., of NCI’s Cancer Prevention
Studies Branch. “Because zinc is maintained in a state of
equilibrium, just like body temperature, the readings will tend
to be similar. Calculating zinc from intake of meat and other dietary
sources isn’t very sensitive either since other compounds,
like phytates in whole grains, 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 the elements in the sample to fluoresce, or glow, with
a characteristic energy signature. “This allowed us to measure
element concentrations directly in the tissue of interest,” said
Abnet, “so it should be the best indicator of the 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 high risk
for squamous esophageal cancer and tend to consume little meat and a lot of whole
grain, and therefore are more likely to be zinc deficient. An earlier publication
estimated that residents of this region get only 62 to 72 percent of the U.S.
dietary recommendations for zinc, whereas most Americans meet current dietary
A subset of the population underwent endoscopy with biopsy in 1985, and the NCI
team, with the aid of Barry Lai, Ph.D., at Argonne National Laboratories, Argonne,
Ill., examined these specimens. They measured zinc, copper, iron, nickel and
sulfur levels in samples from 60 subjects who developed esophageal squamous cell
carcinoma during the 16 year follow-up and from 72 histology-matched subjects
at the start of the study who did not develop the disease.
The average tissue zinc concentration was significantly lower in subjects who
developed esophageal cancer than in control subjects (44 ng/cm2 compared to 57
ng/cm2). When the researchers ranked the study participants by quartiles based
on zinc concentration, they found that those in the highest quartile had a 5-fold
lower risk of developing esophageal cancer than those in the lowest quartile.
Overall, 90 percent of subjects in the highest quartile were alive and cancer-free
after 16 years, while only 65 percent of the subjects in the lowest quartile
were alive and cancer-free. There were no consistent associations with cancer
risk for any of the other elements studied.
These findings establish an initial connection between zinc and esophageal squamous
cell carcinoma in humans, although further research is needed to ensure this
association is more than a local phenomenon in an area of extreme zinc deficiency.
However, Abnet believes the technique itself holds great promise for future element
studies. “X-ray fluorescence spectroscopy has many advantages,” said
Abnet. “You can apply it to most elements and you only need a tiny tissue
sample. Also, it doesn’t damage the tissue, so you can make multiple measurements
on one sample.” Abnet also noted that they successfully measured samples
collected and embedded in paraffin in 1985, demonstrating that other researchers
could apply this technique to archived tissue samples.
For more information about cancer, please visit the NCI Web site
at http://www.cancer.gov or call NCI's Cancer Information Service
at 1-800-4-CANCER (1-800-422-6237).
* Christian C. Abnet, Barry Lai, You-Lin Qiao, Stefan Vogt, Xian-Mao
Luo, Philip R. Taylor, Zhi-Wei Dong, Steven D. Mark, Sanford M.
Dawsey. Zinc concentration in esophageal biopsy specimens measured
by X-ray fluorescence and esophageal cancer risk. Journal of the
National Cancer Institute, 2005; February 16, 2005, 97(4).