Pala V, Agnoli C, Cavalleri A, Rinaldi S, Orlandi R, Segrado F, Venturelli E, Vinceti M, Krogh V, Sieri S.
Cancer Epidemiol Biomarkers Prev. 2022 Mar 4:cebp.1252.2021. doi: 10.1158/1055-9965.EPI-21-1252
Abstract
Background: Case-control studies show that copper (Cu) is high and zinc (Zn) low in blood and urine of breast cancer (BC) women compared to controls.
Methods: To assess whether pre-diagnostic Cu and Zn are associated with BC risk, odds ratios (OR) of BC according to Cu, Zn, and Cu/Zn ratio in plasma and urine were estimated in a nested case-control study within the ORDET cohort, using conditional logistic regression adjusted for multiple variables: First 496 BC cases and matched controls, diagnosed {greater than or equal to} 2 years after recruitment (to eliminate reverse causation) were analyzed. Then all eligible cases/controls were analyzed with stratification into years from recruitment to diagnosis.
Results: For women diagnosed {greater than or equal to} 2 years, compared to lowest tertiles, BC risk was higher in the highest tertile of plasma Cu/Zn ratio (OR:1.75; 95%CI): 1.21, 2.54) and the highest tertile of both plasma and urine Cu/Zn ratio (OR: 2.37; 95%CI: 1.32, 4.25). Risk did not vary with ER/PR/HER2 status. For women diagnosed <2 years, high Cu/Zn ratio was strongly associated with BC risk.
Conclusions: Our prospective findings suggest that increased Cu/Zn ratio in plasma and urine may be both an early marker of, and a risk factor for, BC development. Further studies are justified to confirm or otherwise our results and to investigate mechanisms.
Impact: Our finding that pre-diagnostic Cu/Zn ratio is a strong risk factor for BC development deserves further investigation and if confirmed might open the way to interventions to reduce BC risk in women with disrupted Cu/Zn homeostasis.