Urinary metallomics as a novel biomarker discovery platform: Breast cancer as a case study

Background: Urinary metallomics is presented here as a new "omics" approach that aims to facilitate personalized cancer screening and prevention by improving our understanding of urinary metals in disease. Methods: Twenty-two urinary metals were examined with inductively-coupled plasma-mass spectrometry in 138 women newly diagnosed with breast cancer and benign conditions. Urinary metals from spot urine samples were adjusted to renal dilution using urine specific gravity. Results: Two urinary metals, copper (P-value = 0.036) and lead (P-value = 0.003), were significantly increased in the urine of breast cancer patients. A multivariate model that comprised copper, lead, and patient age afforded encouraging discriminatory power (AUC: 0.728, P-value < 0.0005), while univariate models of copper (61.7% sensitivity, 50.0% specificity) and lead (76.6% sensitivity, 51.2% specificity) at optimized cutoff thresholds compared favorably with other breast cancer diagnostic modalities such as mammography. Correlations found among various metals suggested potential geographic and dietary influences on the urine metallome that warrant further investigation. Conclusions: This proof-of-concept work introduces urinary metallomics as a noninvasive, potentially transformative "omics" approach to early cancer detection. Urinary copper and lead have also been preliminarily identified as potential breast cancer biomarkers. (C) 2015 Elsevier B.V. All rights reserved.