Studies on Association Between Copper Excess, Zinc Deficiency and TP53 Mutations in Esophageal Squamous Cell Carcinoma From Kashmir Valley, India-A High Risk Area

Trace element deficiency or excess is implicated in the development or progression in some cancers. Here we report the elevated levels of copper and low level of zinc in the plasma of esophageal cancer patients in Kashmir India- a high incidence area. The average level of copper was significantly higher for patients than for controls (p<0.0001) with a mean concentration of 169 μg/dl and 149 μg/dl for patients and controls, respectively. In contrast, the average level of zinc in patients was significantly lower than in controls (p<0.0001) with a mean concentration of 86.8 μg/dl and 96.1 μg/dl for patients and controls, respectively. No significant difference in copper and zinc levels was observed for different age groups in controls or patients. For controls, the level of copper was not significantly different in males and females (median: 155 μg/dl for males and 144 μg/dl for females, p=0.10), but we observed a higher level of zinc in females (median: 90.5 μg/dl for males and 101 μg/dl for females, p=0.03). Copper or zinc concentrations were not significantly associated with gender, tumor site, green tea with salt (nun chai) consumption, smoking habits or snuff in cases. Patients with poorly differentiated tumors had a higher copper concentration than those with moderately or well-differentiated tumors (p<0.0001). No association was found between copper concentration and TP53 mutation status but patients with TP53 mutant tumor had lower zinc levels than those with no mutation. Our results point towards a role of the trace element imbalance in the esophageal tumorigenesis in high risk Kashmiri population exposed to a range of nitroso compounds or their precursors. Further prospective cohort studies are warranted to determine whether change in the plasma zinc and copper homeostasis may represent an independent risk factor for this malignancy as well as possible target for preventive intervention.