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Int J Cancer. 2018 Apr 26. doi: 10.1002/ijc.31563. [Epub ahead of print]

A prospective evaluation of plasma polyphenol levels and colon cancer risk.

Author information

1
Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France.
2
Unit of Nutrition and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.
3
CESP, INSERM U1018, Univ. Paris-Sud, UVSQ, Université Paris-Saclay, Villejuif Cedex, France.
4
Université Paris Sud and Gastroenterology Unit, Hôpitaux Universitaires Paris Sud, CHU de Bicêtre, AP-HP, Le Kremlin Bicêtre, France.
5
Gustave Roussy, Espace Maurice Tubiana, Villejuif Cedex, France.
6
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
7
Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbrücke, Germany.
8
Department of Epidemiology, Nutrition, Immunity and Metabolism Start-up Lab, Potsdam-Rehbrücke, Germany.
9
Danish Cancer Society Research Center, Copenhagen, Denmark.
10
Department of Public Health, Aarhus University, Aarhus, Denmark.
11
Public Health Directorate, Asturias, Spain.
12
Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria ibs.GRANADA. Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain.
13
CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
14
Osakidetza/Basque Health Service, Breast Cancer Screening Program, Bilbao, Spain.
15
Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain.
16
Navarra Public Health Institute, Pamplona, Spain.
17
Navarra Institute for Health Research (IdiSNA), Pamplona, Spain.
18
Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
19
Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
20
Hellenic Health Foundation, Athens, Greece.
21
Pulmonary Medicine Department, School of Medicine, National and Kapodistrian University of Athens, "ATTIKON" University Hospital, Haidari, Greece.
22
Cancer Risk Factors and Life-Style Epidemiology Unit, Cancer Research and Prevention Institute-ISPO, Florence, Italy.
23
Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
24
Cancer Registry and Histopathology Department, "Civic - M.P. Arezzo" Hospital, ASP Ragusa, Ragusa, Italy.
25
Unit of Cancer Epidemiology, , Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), Turin, Italy.
26
Dipartimento di Medicina Clinica e Sperimentale, Federico II University, Naples, Italy.
27
Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), PO Box 1, Bilthoven, BA, 3720, The Netherlands.
28
Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands.
29
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
30
Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
31
Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
32
MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
33
Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden.
34
Department of Odontology, Umeå University, Umeå, Sweden.
35
Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, Ioannina, Greece.

Abstract

Polyphenols have been shown to exert biological activity in experimental models of colon cancer; however, human data linking specific polyphenols to colon cancer is limited. We assessed the relationship between pre-diagnostic plasma polyphenols and colon cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition study. Using high pressure liquid chromatography coupled to tandem mass spectrometry, we measured concentrations of 35 polyphenols in plasma from 809 incident colon cancer cases and 809 matched controls. We used multivariable adjusted conditional logistic regression models that included established colon cancer risk factors. The false discovery rate (qvalues ) was computed to control for multiple comparisons. All statistical tests were two-sided. After false discovery rate correction and in continuous log2 -transformed multivariable models, equol (odds ratio [OR] per log2 -value, 0.86, 95% confidence interval [95% CI] = 0.79-0.93; qvalue  = 0.01) and homovanillic acid (OR per log2 -value, 1.46, 95% CI = 1.16-1.84; qvalue  = 0.02) were associated with colon cancer risk. Comparing extreme fifths, equol concentrations were inversely associated with colon cancer risk (OR = 0.61, 95% CI = 0.41-0.91, ptrend  = 0.003), while homovanillic acid concentrations were positively associated with colon cancer development (OR = 1.72, 95% CI = 1.17-2.53, ptrend  < 0.0001). No heterogeneity for these associations was observed by sex and across other colon cancer risk factors. The remaining polyphenols were not associated with colon cancer risk. Higher equol concentrations were associated with lower risk, and higher homovanillic acid concentrations were associated with greater risk of colon cancer. These findings support a potential role for specific polyphenols in colon tumorigenesis.

KEYWORDS:

EPIC; biomarkers; colon cancer; nested case-control study; polyphenols

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