Prediagnostic Levels of Copper and Zinc and Breast Cancer Risk in the ORDET Cohort.


Journal

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
ISSN: 1538-7755
Titre abrégé: Cancer Epidemiol Biomarkers Prev
Pays: United States
ID NLM: 9200608

Informations de publication

Date de publication:
01 06 2022
Historique:
received: 29 10 2021
revised: 22 01 2022
accepted: 18 02 2022
pubmed: 8 3 2022
medline: 3 6 2022
entrez: 7 3 2022
Statut: ppublish

Résumé

Case-control studies show that copper (Cu) is high and zinc (Zn) low in blood and urine of women with breast cancer compared with controls. To assess whether prediagnostic Cu and Zn are associated with breast cancer risk, OR of breast cancer according to Cu, Zn, and Cu/Zn ratio in plasma and urine was estimated in a nested case-control study within the ORDET cohort, using conditional logistic regression adjusted for multiple variables: First 496 breast cancer cases and matched controls, diagnosed ≥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. For women diagnosed ≥2 years, compared with lowest tertiles, breast cancer 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 breast cancer risk. 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, breast cancer development. Further studies are justified to confirm or otherwise our results and to investigate mechanisms. Our finding that prediagnostic Cu/Zn ratio is a strong risk factor for breast cancer development deserves further investigation and, if confirmed, might open the way to interventions to reduce breast cancer risk in women with disrupted Cu/Zn homeostasis.

Sections du résumé

BACKGROUND
Case-control studies show that copper (Cu) is high and zinc (Zn) low in blood and urine of women with breast cancer compared with controls.
METHODS
To assess whether prediagnostic Cu and Zn are associated with breast cancer risk, OR of breast cancer according to Cu, Zn, and Cu/Zn ratio in plasma and urine was estimated in a nested case-control study within the ORDET cohort, using conditional logistic regression adjusted for multiple variables: First 496 breast cancer cases and matched controls, diagnosed ≥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 ≥2 years, compared with lowest tertiles, breast cancer 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 breast cancer 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, breast cancer development. Further studies are justified to confirm or otherwise our results and to investigate mechanisms.
IMPACT
Our finding that prediagnostic Cu/Zn ratio is a strong risk factor for breast cancer development deserves further investigation and, if confirmed, might open the way to interventions to reduce breast cancer risk in women with disrupted Cu/Zn homeostasis.

Identifiants

pubmed: 35255128
pii: 682049
doi: 10.1158/1055-9965.EPI-21-1252
doi:

Substances chimiques

Copper 789U1901C5
Zinc J41CSQ7QDS

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1209-1215

Informations de copyright

©2022 American Association for Cancer Research.

Auteurs

Valeria Pala (V)

Epidemiology and Prevention Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Claudia Agnoli (C)

Epidemiology and Prevention Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Adalberto Cavalleri (A)

Epidemiology and Prevention Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Sabina Rinaldi (S)

Nutrition and Metabolism Branch, IARC-WHO, 69372, Lyon Cedex 08, France.

Rosaria Orlandi (R)

Molecular Targeting Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Francesco Segrado (F)

Molecular Targeting Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Elisabetta Venturelli (E)

Epidemiology and Prevention Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Marco Vinceti (M)

Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts.

Vittorio Krogh (V)

Epidemiology and Prevention Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Sabina Sieri (S)

Epidemiology and Prevention Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

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