Raul Zamora-Ros1, Leila Lujan-Barroso1, David Achaintre2, Silvia Franceschi3, Cecilie Kyrø4, Kim Overvad5, Anne Tjønneland4,6, Therese Truong7,8, Lucie Lecuyer7,8, Marie-Christine Boutron-Ruault7,8, Verena Katzke9, Theron S Johnson9, Matthias B Schulze10,11, Antonia Trichopoulou12, Eleni Peppa12, Carlo La Vechia12,13, Giovanna Masala14, Valeria Pala15, Salvatore Panico16, Rosario Tumino17, Fulvio Ricceri18,19, Guri Skeie20, J Ramón Quirós21, Miguel Rodriguez-Barranco22,23,24,25, Pilar Amiano24,26, María-Dolores Chirlaque24,27, Eva Ardanaz24,28,29, Martin Almquist30, Joakim Hennings31, Roel Vermeulen32,33, Nicholas J Wareham34, Tammy Y N Tong35, Dagfinn Aune36,37,38, Graham Byrnes2, Elisabete Weiderpass2, Augustin Scalbert2, Sabina Rinaldi2, Antonio Agudo1. 1. Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain. 2. International Agency for Research on Cancer (IARC-WHO), Lyon, France. 3. Oncology Referral Center (CRO), Aviano National Cancer Institute, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Aviano, Italy. 4. Danish Cancer Society Research Center, Copenhagen, Denmark. 5. Department of Public Health, Aarhus University, Aarhus, Denmark. 6. Department of Public Health, University of Copenhagen, Copenhagen, Denmark. 7. Versailles Saint-Quentin-en-Yvelines University (UVSQ), Université Paris-Saclay, Institut National de la Santé et de la Recherche Médicale, Centre for Research in Epidemiology and Population Health (CESP), Villejuif, France. 8. Gustave Roussy, Villejuif, France. 9. Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. 10. Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. 11. Institute of Nutritional Sciences, University of Potsdam, Nuthetal, Germany. 12. Hellenic Health Foundation, Athens, Greece. 13. Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy. 14. Cancer Risk Factors and Lifestyle Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network-ISPRO, Florence, Italy. 15. Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 16. Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy. 17. Cancer Registry and Histopathology Department, "Civic-MP Arezzo" Hospital, ASP Ragusa, Ragusa, Italy. 18. Department of Clinical and Biological Sciences, University of Turin, Turin, Italy. 19. Unit of Epidemiology, Regional Health Service ASL TO3, Grugliasco, Turin, Italy. 20. Department of Community Medicine, UiT the Arctic University of Norway, Tromsø, Norway. 21. Public Health Directorate, Asturias, Spain. 22. Andalusian School of Public Health, Granada, Spain. 23. Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain. 24. CIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain. 25. Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain. 26. Public Health Division of Gipuzkoa, BioDonostia Research Institute, Donostia-San Sebastian, Spain. 27. Department of Epidemiology, Murcia Regional Health Council, Instituto Murciano de Investigación Biosanitaria (IMIB)-Arrixaca, Murcia, Spain. 28. Navarra Public Health Institute, Pamplona, Spain. 29. Navarra Institute for Health Research (IdiSNA), Pamplona, Spain. 30. Department of Surgery, Endocrine-Sarcoma Unit, Skåne University Hospital, Lund, Sweden. 31. Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden. 32. Institute of Risk Assessment Sciences, Utrecht University, Utrecht, Netherlands. 33. Department of Public Health, University Medical Center Utrecht, Utrecht, Netherlands. 34. Medical Research Council (MRC) Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom. 35. Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. 36. Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom. 37. Department of Nutrition, Bjørknes University College, Oslo, Norway. 38. Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway.
Abstract
BACKGROUND: Polyphenols are natural compounds with anticarcinogenic properties in cellular and animal models, but epidemiological evidence determining the associations of these compounds with thyroid cancer (TC) is lacking. OBJECTIVES: The aim of this study was to evaluate the relations between blood concentrations of 36 polyphenols and TC risk in EPIC (the European Prospective Investigation into Cancer and Nutrition). METHODS: A nested case-control study was conducted on 273 female cases (210 papillary, 45 follicular, and 18 not otherwise specified TC tumors) and 512 strictly matched controls. Blood polyphenol concentrations were analyzed by HPLC coupled to tandem MS after enzymatic hydrolysis. RESULTS: Using multivariable-adjusted conditional logistic regression models, caffeic acid (ORlog2: 0.55; 95% CI: 0.33, 0.93) and its dehydrogenated metabolite, 3,4-dihydroxyphenylpropionic acid (ORlog2: 0.84; 95% CI: 0.71, 0.99), were inversely associated with differentiated TC risk. Similar results were observed for papillary TC, but not for follicular TC. Ferulic acid was also inversely associated only with papillary TC (ORlog2: 0.68; 95% CI: 0.51, 0.91). However, none of these relations was significant after Bonferroni correction for multiple testing. No association was observed for any of the remaining polyphenols with total differentiated, papillary, or follicular TC. CONCLUSIONS: Blood polyphenol concentrations were mostly not associated with differentiated TC risk in women, although our study raises the possibility that high blood concentrations of caffeic, 3,4-dihydroxyphenylpropionic, and ferulic acids may be related to a lower papillary TC risk.
BACKGROUND: Polyphenols are natural compounds with anticarcinogenic properties in cellular and animal models, but epidemiological evidence determining the associations of these compounds with thyroid cancer (TC) is lacking. OBJECTIVES: The aim of this study was to evaluate the relations between blood concentrations of 36 polyphenols and TC risk in EPIC (the European Prospective Investigation into Cancer and Nutrition). METHODS: A nested case-control study was conducted on 273 female cases (210 papillary, 45 follicular, and 18 not otherwise specified TC tumors) and 512 strictly matched controls. Blood polyphenol concentrations were analyzed by HPLC coupled to tandem MS after enzymatic hydrolysis. RESULTS: Using multivariable-adjusted conditional logistic regression models, caffeic acid (ORlog2: 0.55; 95% CI: 0.33, 0.93) and its dehydrogenated metabolite, 3,4-dihydroxyphenylpropionic acid (ORlog2: 0.84; 95% CI: 0.71, 0.99), were inversely associated with differentiated TC risk. Similar results were observed for papillary TC, but not for follicular TC. Ferulic acid was also inversely associated only with papillary TC (ORlog2: 0.68; 95% CI: 0.51, 0.91). However, none of these relations was significant after Bonferroni correction for multiple testing. No association was observed for any of the remaining polyphenols with total differentiated, papillary, or follicular TC. CONCLUSIONS: Blood polyphenol concentrations were mostly not associated with differentiated TC risk in women, although our study raises the possibility that high blood concentrations of caffeic, 3,4-dihydroxyphenylpropionic, and ferulic acids may be related to a lower papillary TC risk.