Pre-diagnostic copper and zinc biomarkers and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort

作者：Magdalena Stępień, Mazda Jenab, Heinz Freisling, Niels‐Peter Becker, Magdalena Czuban, Anne Marie Tjønneland, Anja Olsen, Kim Overvad, Marie‐Christine Boutron‐Ruault, Francesca Romana Mancini, Isabelle Savoye, Verena Andrea Katzke, Tilman E. Kuhn, Heiner Boeing, Khalid Javed Iqbal, Antonia Trichopoulou, Christina Bamia, Philippos Orfanos, Domenico Palli, Sabina Sieri, Rosario Tumino, Alessio Naccarati, Salvatore Panico, H. Bas Bueno‐de‐Mesquita, Petra H. M. Peeters, Elisabete Weiderpass, Susana Merino, Paula Gabriela Jakszyn, María‐José Sánchez, Miren Dorronsoro, José María Huerta, Aurelio Barricarte, Stina Bodén, Behany van Guelpen, Nick Wareham, Kay‐Tee Khaw, Kathryn Erica Bradbury, Amanda Jane Cross, Lutz Schomburg, David J. Hughes · 发表于：Carcinogenesis · 年份：2017 · DOI：10.1093/carcin/bgx051 · 被引用次数：169 · 研究领域：Trace Elements in Health、Drug Transport and Resistance Mechanisms、Heavy Metal Exposure and Toxicity

Adequate intake of copper and zinc, two essential micronutrients, are important for antioxidant functions. Their imbalance may have implications for development of diseases like colorectal cancer (CRC), where oxidative stress is thought to be etiologically involved. As evidence from prospective epidemiologic studies is lacking, we conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to investigate the association between circulating levels of copper and zinc, and their calculated ratio, with risk of CRC development. Copper and zinc levels were measured by reflection X-ray fluorescence spectrometer in 966 cases and 966 matched controls. Multivariable adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression and are presented for the fifth versus first quintile. Higher circulating concentration of copper was associated with a raised CRC risk (OR = 1.50; 95% CI: 1.06, 2.13; P-trend = 0.02) whereas an inverse association with cancer risk was observed for higher zinc levels (OR = 0.65; 95% CI: 0.43, 0.97; P-trend = 0.07). Consequently, the ratio of copper/zinc was positively associated with CRC (OR = 1.70; 95% CI: 1.20, 2.40; P-trend = 0.0005). In subgroup analyses by follow-up time, the associations remained statistically significant only in those diagnosed within 2 years of blood collection. In conclusion, these data suggest that copper or copper levels ...