Abnet CC et al. (2005) Zinc concentration in esophageal biopsy specimens measured by X-ray fluorescence and esophageal cancer risk. J Natl Cancer Inst 97: 301–306

Animal studies have linked zinc deficiency to an increased risk of esophageal cancer, which is thought to be mediated by certain nitrosamines. This effect has been difficult to demonstrate in humans, however, because neither blood levels of zinc nor estimates of dietary zinc intake provide an accurate picture of the concentration of this mineral in the body's tissues. Abnet and co-workers have addressed this problem by measuring the concentration of zinc and other minerals directly in esophageal biopsy specimens, using X-ray fluorescence spectroscopy.

The samples were obtained from a population in Linzhou, China, where the diet contains large quantities of whole grain and little meat and therefore tends to be low in zinc. A total of 60 specimens were from subjects who subsequently developed esophageal squamous cell carcinoma during the 16-year Dysplasia Trial: 72 samples were from individuals who did not develop the disease. Baseline concentrations of zinc, copper, iron, nickel, and sulfur were measured by X-ray fluorescence at two sites within each tissue sample.

During the 16-year follow-up, participants in the highest zinc quartile were at a significantly lower risk of developing esophageal cancer than those in the lowest quartile (hazard ratio 0.21, 95% CI 0.065–0.680). The corresponding disease-free survival rates were 90% and 65% for the two groups, respectively, and the association was statistically significant across quartiles (P = 0.015). Sulfur concentration also appeared to be inversely related to esophageal cancer risk when the highest and lowest quartiles were compared, but this association was not significant across quartiles. None of the other minerals tested showed any such relationship.

In summary, the study provides evidence for the role of zinc deficiency in the development of esophageal squamous cell carcinoma in humans. The authors note that the approach described could be used to study other nutritional or toxic elements and their relationship with disease.