Zinc stable isotopes in urine as diagnostic for cancer of secretory organs.
Schilling K., Moore RET., Sullivan KV., Capper MS., Rehkämper M., Goddard K., Ion C., Coombes RC., Vesty-Edwards L., Lamb AD., Halliday AN., Larner F.
Breast, prostatic and pancreatic cancers alter the zinc (Zn) metabolism. Combined analyses of urinary Zn concentrations ([Zn]) and Zn stable isotope compositions (δ66Zn) may provide a non-invasive approach for tracing malignancy-induced Zn dyshomeostasis. In this study, we measured [Zn] and δ66Zn in urine from prostate (n = 22), breast (n = 16) and from women with benign breast disease (n = 14) and compared those to age-matched healthy controls (22-49 yrs or 50 + yrs) and published data for pancreatic cancer (n = 17). Our results show cancer-induced changes are reflected in higher urinary [Zn] and lower urinary δ66Zn for pancreatic and prostate cancer and benign breast disease when compared to healthy controls. For prostate cancer, low [Zn] and high δ66Zn for patients of low-risk disease progresses towards high [Zn] and low δ66Zn for the higher-risk patients, demonstrates that [Zn] and δ66Zn in urine could serve as a reliable prognostic tool. Urinary excretion of isotopically light Zn by patients with prostatic and pancreatic cancer is probably the result of increased reactive oxygen species in cancerous cells, which limits the scavenging of hydroxyl radicals and thus facilitates the oxidation of metalloproteins with sulfur-rich ligands. Urine from malignant breast cancer patients shows undistinguishable δ66Zn to healthy controls, implying that the expression of metalloproteins with sulfur-rich ligands is stronger in breast cancer tissues. In conclusion, urinary δ66Zn may provide a non-invasive diagnostic tool for pancreatic cancer and support disease prognosis for prostate cancer. These findings should translate to comprehensive transverse and longitudinal cohort studies in future.