. 2018 Nov;33(11):1063-1075.

doi: 10.1007/s10654-018-0408-6. Epub 2018 May 15.

Dietary intake of total polyphenol and polyphenol classes and the risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Raul Zamora-Ros¹, Valerie Cayssials², Mazda Jenab³, Joseph A Rothwell³, Veronika Fedirko⁴, Krasimira Aleksandrova⁵, Anne Tjønneland⁶, Cecilie Kyrø⁶, Kim Overvad⁷, Marie-Christine Boutron-Ruault^{8

9}, Franck Carbonnel^{8

9

10}, Yahya Mahamat-Saleh^{8

9}, Rudolf Kaaks¹¹, Tilman Kühn¹¹, Heiner Boeing⁵, Antonia Trichopoulou^{12

13}, Elissavet Valanou¹², Effie Vasilopoulou^{12

13}, Giovanna Masala¹⁴, Valeria Pala¹⁵, Salvatore Panico¹⁶, Rosario Tumino¹⁷, Fulvio Ricceri^{18

19}, Elisabete Weiderpass^{20

21

22

23}, Marko Lukic²⁰, Torkjel M Sandanger²⁰, Cristina Lasheras²⁴, Antonio Agudo², Maria-Jose Sánchez^{25

26}, Pilar Amiano^{26

27}, Carmen Navarro^{26

28

29}, Eva Ardanaz^{26

30

31}, Emily Sonestedt³², Bodil Ohlsson³³, Lena Maria Nilsson³⁴, Martin Rutegård³⁵, Bas Bueno-de-Mesquita^{36

37

38

39}, Petra H Peeters^{38

40}, Kay-Thee Khaw⁴¹, Nicholas J Wareham⁴², Kathryn Bradbury⁴³, Heinz Freisling³, Isabelle Romieu³, Amanda J Cross³⁸, Paolo Vineis³⁸, Augustin Scalbert³

Affiliations

¹ Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), Av Gran Via 199-203, 08908, L'Hospitalet De Llobregat, Barcelona, Spain. rzamora@iconcologia.net.
² Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), Av Gran Via 199-203, 08908, L'Hospitalet De Llobregat, Barcelona, Spain.
³ Nutrition and Metabolism Section, International Agency for Research on Cancer (IARC), Lyon, France.
⁴ Rollins School of Public Health, Winship Cancer Institute, Emory University, Atlanta, GA, USA.
⁵ Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
⁶ Danish Cancer Society Research Center, Copenhagen, Denmark.
⁷ Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark.
⁸ CESP (Centre de Recherche en Epidémiologie et Santé des Populations), Université Paris-Sud, UVSQ, INSERM, Université Paris-Saclay, Villejuif, France.
⁹ Institut Gustave Roussy, Villejuif, France.
¹⁰ Department of Gastroenterology, Bicêtre University Hospital, Assistance Publique des Hôpitaux de Paris, Le Kremlin Bicêtre, France.
¹¹ Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
¹² Hellenic Health Foundation, Athens, Greece.
¹³ WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
¹⁴ Cancer Risk Factors and Life-Style Epidemiology Unit, Cancer Research and Prevention Institute - ISPO, Florence, Italy.
¹⁵ Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
¹⁶ Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy.
¹⁷ Cancer Registry and Histopathology Unit, "Civic M.P. Arezzo" Hospital, ASP Ragusa, Italy.
¹⁸ Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.
¹⁹ Unit of Epidemiology, Regional Health Service ASL TO3, Grugliasco (TO), Italy.
²⁰ Department of Community Medicine, Faculty of Health Sciences, UiT, The Artic University of Tromsø, Tromsø, Norway.
²¹ Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway.
²² Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
²³ Genetic Epidemiology Group, Folkhälsan Research Center and Faculty of Medicine, University of Helsinki, Helsinki, Finland.
²⁴ Department of Functional Biology, Faculty of Medicine, University of Oviedo, Oviedo, Spain.
²⁵ Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs.Granada. Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain.
²⁶ CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
²⁷ Public Health Division of Gipuzkoa, Regional Government of the Basque Country, Donostia, Spain.
²⁸ Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain.
²⁹ Department of Health and Social Sciences, Universidad de Murcia, Murcia, Spain.
³⁰ Navarra Public Health Institute, Pamplona, Spain.
³¹ IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.
³² Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
³³ Department of Internal Medicine, Skåne University Hospital, Lund University, Malmö, Sweden.
³⁴ Public Health and Clinical Medicine, Nutritional Research, Umeå University, Umeå, Sweden.
³⁵ Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden.
³⁶ Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
³⁷ Department of Gastroenterology and Hepatology, University Medical Center, Utrecht, The Netherlands.
³⁸ Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, UK.
³⁹ Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
⁴⁰ Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
⁴¹ Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
⁴² MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, UK.
⁴³ Cancer Epidemiology Unit, University of Oxford, Oxford, UK.

PMID: 29761424
PMCID: PMC6760973
DOI: 10.1007/s10654-018-0408-6

Dietary intake of total polyphenol and polyphenol classes and the risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Raul Zamora-Ros et al. Eur J Epidemiol. 2018 Nov.

. 2018 Nov;33(11):1063-1075.

doi: 10.1007/s10654-018-0408-6. Epub 2018 May 15.

Authors

Affiliations

¹ Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), Av Gran Via 199-203, 08908, L'Hospitalet De Llobregat, Barcelona, Spain. rzamora@iconcologia.net.
² Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), Av Gran Via 199-203, 08908, L'Hospitalet De Llobregat, Barcelona, Spain.
³ Nutrition and Metabolism Section, International Agency for Research on Cancer (IARC), Lyon, France.
⁴ Rollins School of Public Health, Winship Cancer Institute, Emory University, Atlanta, GA, USA.
⁵ Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
⁶ Danish Cancer Society Research Center, Copenhagen, Denmark.
⁷ Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark.
⁸ CESP (Centre de Recherche en Epidémiologie et Santé des Populations), Université Paris-Sud, UVSQ, INSERM, Université Paris-Saclay, Villejuif, France.
⁹ Institut Gustave Roussy, Villejuif, France.
¹⁰ Department of Gastroenterology, Bicêtre University Hospital, Assistance Publique des Hôpitaux de Paris, Le Kremlin Bicêtre, France.
¹¹ Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
¹² Hellenic Health Foundation, Athens, Greece.
¹³ WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
¹⁴ Cancer Risk Factors and Life-Style Epidemiology Unit, Cancer Research and Prevention Institute - ISPO, Florence, Italy.
¹⁵ Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
¹⁶ Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy.
¹⁷ Cancer Registry and Histopathology Unit, "Civic M.P. Arezzo" Hospital, ASP Ragusa, Italy.
¹⁸ Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.
¹⁹ Unit of Epidemiology, Regional Health Service ASL TO3, Grugliasco (TO), Italy.
²⁰ Department of Community Medicine, Faculty of Health Sciences, UiT, The Artic University of Tromsø, Tromsø, Norway.
²¹ Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway.
²² Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
²³ Genetic Epidemiology Group, Folkhälsan Research Center and Faculty of Medicine, University of Helsinki, Helsinki, Finland.
²⁴ Department of Functional Biology, Faculty of Medicine, University of Oviedo, Oviedo, Spain.
²⁵ Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs.Granada. Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain.
²⁶ CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
²⁷ Public Health Division of Gipuzkoa, Regional Government of the Basque Country, Donostia, Spain.
²⁸ Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain.
²⁹ Department of Health and Social Sciences, Universidad de Murcia, Murcia, Spain.
³⁰ Navarra Public Health Institute, Pamplona, Spain.
³¹ IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.
³² Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
³³ Department of Internal Medicine, Skåne University Hospital, Lund University, Malmö, Sweden.
³⁴ Public Health and Clinical Medicine, Nutritional Research, Umeå University, Umeå, Sweden.
³⁵ Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden.
³⁶ Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
³⁷ Department of Gastroenterology and Hepatology, University Medical Center, Utrecht, The Netherlands.
³⁸ Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, UK.
³⁹ Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
⁴⁰ Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
⁴¹ Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
⁴² MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, UK.
⁴³ Cancer Epidemiology Unit, University of Oxford, Oxford, UK.

PMID: 29761424
PMCID: PMC6760973
DOI: 10.1007/s10654-018-0408-6

Abstract

Polyphenols may play a chemopreventive role in colorectal cancer (CRC); however, epidemiological evidence supporting a role for intake of individual polyphenol classes, other than flavonoids is insufficient. We evaluated the association between dietary intakes of total and individual classes and subclasses of polyphenols and CRC risk and its main subsites, colon and rectum, within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The cohort included 476,160 men and women from 10 European countries. During a mean follow-up of 14 years, there were 5991 incident CRC cases, of which 3897 were in the colon and 2094 were in the rectum. Polyphenol intake was estimated using validated centre/country specific dietary questionnaires and the Phenol-Explorer database. In multivariable-adjusted Cox regression models, a doubling in total dietary polyphenol intake was not associated with CRC risk in women (HR_log2 = 1.06, 95% CI 0.99-1.14) or in men (HR_log2 = 0.97, 95% CI 0.90-1.05), respectively. Phenolic acid intake, highly correlated with coffee consumption, was inversely associated with colon cancer in men (HR_log2 = 0.91, 95% CI 0.85-0.97) and positively associated with rectal cancer in women (HR_log2 = 1.10, 95% CI 1.02-1.19); although associations did not exceed the Bonferroni threshold for significance. Intake of other polyphenol classes was not related to colorectal, colon or rectal cancer risks. Our study suggests a possible inverse association between phenolic acid intake and colon cancer risk in men and positive with rectal cancer risk in women.

Keywords: Colorectal cancer; Diet; EPIC; Intake; Polyphenols; Prospective cohort.

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Conflict of interest statement

Conflict of Interest

The authors declare that they have no conflict of interest.

Figures

**Figure 1**
Hazard ratios and (95% CI) for colorectal cancer and subsites by sex and length of follow-up, according to double the intake (log₂) of total polyphenol, flavonoid, and phenolic acid in women (black circles) and men (grey circles) from the EPIC study.

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Dietary intake of total polyphenol and polyphenol classes and the risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

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Dietary intake of total polyphenol and polyphenol classes and the risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

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