1 TITLE PAGE 1 Title: Pre-diagnostic levels of copper and zinc and breast cancer risk in the ORDET cohort 2 Authors: Valeria Pala 1 *, Claudia Agnoli 1 *, Adalberto Cavalleri 1 , Sabina Rinaldi 2 , Rosaria 3 Orlandi 3 , Francesco Segrado 3 , Elisabetta Venturelli 1 , Marco Vinceti 4,5 , Vittorio Krogh 1 , and Sabina 4 Sieri 1 5 1 Epidemiology and Prevention Unit, Department of Research, Fondazione IRCCS Istituto 6 Nazionale dei Tumori, Milan, Italy. 7 2 Nutrition and Metabolism Branch, IARC-WHO, 69372, Lyon Cedex 08, France. 8 3 Molecular Targeting Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 9 4 Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio 10 Emilia, Modena, Italy. 11 5 Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts, 12 USA. 13 Running Title: Copper, zinc and breast cancer in the ORDET cohort 14 Abbreviations: CI, confidence interval; BMI, body mass index; BC, breast cancer; OR, odds ratio; 15 SD, standard deviation; ER, estrogen receptor; PR, progesterone receptor; HER2, human epidermal 16 growth factor receptor 2. 17 Keywords: breast cancer; copper; zinc; nested case-control study; biomarkers. 18 Funding The Italian Association for Cancer Research (AIRC) provided financial support for this 19 study. Grant No 17572 awarded to S. Sieri. 20 Corresponding author: Valeria Pala, Epidemiology and Prevention Unit, Department of 21 Research, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano 20133 Milan - Italy; E- 22 mail: valeria.pala@istitutotumori.mi.it; Phone +390223903505 23 Conflict of interest statement: All authors declare they have no conflicts of interest 24 IARC/WHO disclaimer: Where authors are identified as personnel of the International Agency 25 for Research on Cancer/World Health Organization, those authors alone are responsible for the 26 Downloaded from http://aacrjournals.org/cebp/article-pdf/doi/10.1158/1055-9965.EPI-21-1252/3053320/epi-21-1252.pdf by guest on 08 March 2022