Adiposity, mediating biomarkers and risk of colon cancer in the European prospective investigation into cancer and nutrition study
Corresponding Author
Krasimira Aleksandrova
Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
Correspondence to: Krasimira Aleksandrova, PhD, MPH, Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert Allee 114-116, 14558 Nuthetal, Germany, Tel.: +49-33200-88-2-712, Fax: +49-33200-88-2-721, E-mail: [email protected]Search for more papers by this authorDagmar Drogan
Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
Search for more papers by this authorHeiner Boeing
Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
Search for more papers by this authorMazda Jenab
International Agency for Research on Cancer (IARC-WHO), Lyon, France
Search for more papers by this authorH. Bas Bueno-de-Mesquita
National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
Department of Gastroenterology and Hepatology, University Medical Center, Utrecht, The Netherlands
Search for more papers by this authorEugene Jansen
National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
Search for more papers by this authorFränzel J.B. van Duijnhoven
National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands
Search for more papers by this authorSabina Rinaldi
International Agency for Research on Cancer (IARC-WHO), Lyon, France
Search for more papers by this authorVeronika Fedirko
International Agency for Research on Cancer (IARC-WHO), Lyon, France
Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA
Search for more papers by this authorIsabelle Romieu
International Agency for Research on Cancer (IARC-WHO), Lyon, France
Search for more papers by this authorRudolf Kaaks
Division of Cancer Epidemiology, German Cancer Research Centre, Heidelberg, Germany
Search for more papers by this authorElio Riboli
Division of Epidemiology, Public Health and Primary Care, Imperial College, London, United Kingdom
Search for more papers by this authorMarc J. Gunter
Division of Epidemiology, Public Health and Primary Care, Imperial College, London, United Kingdom
Search for more papers by this authorDora Romaguera
Division of Epidemiology, Public Health and Primary Care, Imperial College, London, United Kingdom
Search for more papers by this authorSabine Westhpal
Institute of Clinical Chemistry, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany
Search for more papers by this authorKim Overvad
Department of Epidemiology, School of Public Health, Aarhus University, Aarhus, Denmark
Search for more papers by this authorAnne Tjønneland
Department of Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark
Search for more papers by this authorJytte Halkjær
Department of Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark
Search for more papers by this authorMarie-Christine Boutron-Ruault
Inserm, Centre for Research in Epidemiology and Population Health, U1018, Institut Gustave Roussy, and Paris South University, UMRS 1018, Villejuif, France
Search for more papers by this authorFrançoise Clavel-Chapelon
Inserm, Centre for Research in Epidemiology and Population Health, U1018, Institut Gustave Roussy, and Paris South University, UMRS 1018, Villejuif, France
Search for more papers by this authorAnnekatrin Lukanova
Division of Cancer Epidemiology, German Cancer Research Centre, Heidelberg, Germany
Search for more papers by this authorAntonia Trichopoulou
WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece
Hellenic Health Foundation, Athens, Greece
Search for more papers by this authorDimitrios Trichopoulos
Hellenic Health Foundation, Athens, Greece
Department of Epidemiology, Harvard School of Public Health, Boston, MA
Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece
Search for more papers by this authorSalvatore Panico
Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy
Search for more papers by this authorClaudia Agnoli
Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy
Search for more papers by this authorDomenico Palli
Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute-ISPO, Florence, Italy
Search for more papers by this authorRosario Tumino
Cancer Registry and Histopathology Unit, “M.P.Arezzo” Hospital, Ragusa, Italy
Search for more papers by this authorPaolo Vineis
Division of Epidemiology, Public Health and Primary Care, Imperial College, London, United Kingdom
HuGeF Foundation, Turin, Italy
Search for more papers by this authorGenevieve Buckland
Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain
Search for more papers by this authorJosé-Juan Sánchez-Cruz
Andalusian School of Public Health, Granada, Spain
Search for more papers by this authorMiren Dorronsoro
Epidemiology and Health Information, Public Health Division of Gipuzkoa, Basque Regional Health Department, San Sebastian, Spain
Search for more papers by this authorMaría José Tormo Díaz
Servicio de Epidemiología, Department of Epidemiology, Consejería de Sanidad y Politica Social, Murcia, Spain
Regional Health Council, CIBER Epidemiología y Salud Pública (CIBERESP), Spain
Facultad de Medicina de Murcia, Murcia School of Medicine, Murcia, Spain
Search for more papers by this authorAurelio Barricarte
Navarre Public Health Institute, Pamplona, Spain
Search for more papers by this authorPetra H. Peeters
Division of Epidemiology, Public Health and Primary Care, Imperial College, London, United Kingdom
Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands
Search for more papers by this authorAnne M. May
Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands
Search for more papers by this authorGöran Hallmans
Department of Public Health and Clinical Medicine, Nutritional Research, Umeå University, Umeå, Sweden
Search for more papers by this authorRichard Palmqvist
Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden
Search for more papers by this authorFrancesca L. Crowe
Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom
Search for more papers by this authorKay-Tee Khaw
Medical Research Council UK and Cancer Research UK, London, United Kingdom
Search for more papers by this authorNickolas Wareham
Medical Research Council UK and Cancer Research UK, London, United Kingdom
Search for more papers by this authorTobias Pischon
Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
Molecular Epidemiology Group, Max Delbrueck Center for Molecular Medicine (MDC), Berlin-Buch, Germany
Search for more papers by this authorCorresponding Author
Krasimira Aleksandrova
Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
Correspondence to: Krasimira Aleksandrova, PhD, MPH, Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert Allee 114-116, 14558 Nuthetal, Germany, Tel.: +49-33200-88-2-712, Fax: +49-33200-88-2-721, E-mail: [email protected]Search for more papers by this authorDagmar Drogan
Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
Search for more papers by this authorHeiner Boeing
Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
Search for more papers by this authorMazda Jenab
International Agency for Research on Cancer (IARC-WHO), Lyon, France
Search for more papers by this authorH. Bas Bueno-de-Mesquita
National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
Department of Gastroenterology and Hepatology, University Medical Center, Utrecht, The Netherlands
Search for more papers by this authorEugene Jansen
National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
Search for more papers by this authorFränzel J.B. van Duijnhoven
National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands
Search for more papers by this authorSabina Rinaldi
International Agency for Research on Cancer (IARC-WHO), Lyon, France
Search for more papers by this authorVeronika Fedirko
International Agency for Research on Cancer (IARC-WHO), Lyon, France
Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA
Search for more papers by this authorIsabelle Romieu
International Agency for Research on Cancer (IARC-WHO), Lyon, France
Search for more papers by this authorRudolf Kaaks
Division of Cancer Epidemiology, German Cancer Research Centre, Heidelberg, Germany
Search for more papers by this authorElio Riboli
Division of Epidemiology, Public Health and Primary Care, Imperial College, London, United Kingdom
Search for more papers by this authorMarc J. Gunter
Division of Epidemiology, Public Health and Primary Care, Imperial College, London, United Kingdom
Search for more papers by this authorDora Romaguera
Division of Epidemiology, Public Health and Primary Care, Imperial College, London, United Kingdom
Search for more papers by this authorSabine Westhpal
Institute of Clinical Chemistry, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany
Search for more papers by this authorKim Overvad
Department of Epidemiology, School of Public Health, Aarhus University, Aarhus, Denmark
Search for more papers by this authorAnne Tjønneland
Department of Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark
Search for more papers by this authorJytte Halkjær
Department of Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark
Search for more papers by this authorMarie-Christine Boutron-Ruault
Inserm, Centre for Research in Epidemiology and Population Health, U1018, Institut Gustave Roussy, and Paris South University, UMRS 1018, Villejuif, France
Search for more papers by this authorFrançoise Clavel-Chapelon
Inserm, Centre for Research in Epidemiology and Population Health, U1018, Institut Gustave Roussy, and Paris South University, UMRS 1018, Villejuif, France
Search for more papers by this authorAnnekatrin Lukanova
Division of Cancer Epidemiology, German Cancer Research Centre, Heidelberg, Germany
Search for more papers by this authorAntonia Trichopoulou
WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece
Hellenic Health Foundation, Athens, Greece
Search for more papers by this authorDimitrios Trichopoulos
Hellenic Health Foundation, Athens, Greece
Department of Epidemiology, Harvard School of Public Health, Boston, MA
Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece
Search for more papers by this authorSalvatore Panico
Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy
Search for more papers by this authorClaudia Agnoli
Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy
Search for more papers by this authorDomenico Palli
Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute-ISPO, Florence, Italy
Search for more papers by this authorRosario Tumino
Cancer Registry and Histopathology Unit, “M.P.Arezzo” Hospital, Ragusa, Italy
Search for more papers by this authorPaolo Vineis
Division of Epidemiology, Public Health and Primary Care, Imperial College, London, United Kingdom
HuGeF Foundation, Turin, Italy
Search for more papers by this authorGenevieve Buckland
Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain
Search for more papers by this authorJosé-Juan Sánchez-Cruz
Andalusian School of Public Health, Granada, Spain
Search for more papers by this authorMiren Dorronsoro
Epidemiology and Health Information, Public Health Division of Gipuzkoa, Basque Regional Health Department, San Sebastian, Spain
Search for more papers by this authorMaría José Tormo Díaz
Servicio de Epidemiología, Department of Epidemiology, Consejería de Sanidad y Politica Social, Murcia, Spain
Regional Health Council, CIBER Epidemiología y Salud Pública (CIBERESP), Spain
Facultad de Medicina de Murcia, Murcia School of Medicine, Murcia, Spain
Search for more papers by this authorAurelio Barricarte
Navarre Public Health Institute, Pamplona, Spain
Search for more papers by this authorPetra H. Peeters
Division of Epidemiology, Public Health and Primary Care, Imperial College, London, United Kingdom
Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands
Search for more papers by this authorAnne M. May
Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands
Search for more papers by this authorGöran Hallmans
Department of Public Health and Clinical Medicine, Nutritional Research, Umeå University, Umeå, Sweden
Search for more papers by this authorRichard Palmqvist
Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden
Search for more papers by this authorFrancesca L. Crowe
Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom
Search for more papers by this authorKay-Tee Khaw
Medical Research Council UK and Cancer Research UK, London, United Kingdom
Search for more papers by this authorNickolas Wareham
Medical Research Council UK and Cancer Research UK, London, United Kingdom
Search for more papers by this authorTobias Pischon
Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
Molecular Epidemiology Group, Max Delbrueck Center for Molecular Medicine (MDC), Berlin-Buch, Germany
Search for more papers by this authorAbstract
Adiposity is a risk factor for colon cancer, but underlying mechanisms are not well understood. We evaluated the extent to which 11 biomarkers with inflammatory and metabolic actions mediate the association of adiposity measures, waist circumference (WC) and body mass index (BMI), with colon cancer in men and women. We analyzed data from a prospective nested case–control study among 662 incident colon cancer cases matched within risk sets to 662 controls. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. The percent effect change and corresponding CIs were estimated after adjusting for biomarkers shown to be associated with colon cancer risk. After multivariable adjustment, WC was associated with colon cancer risk in men (top vs. bottom tertile RR 1.68, 95% CI 1.06–2.65; ptrend = 0.02) and in women (RR 1.67, 95% CI 1.09–2.56; ptrend = 0.03). BMI was associated with risk only in men. The association of WC with colon cancer was accounted mostly for by three biomarkers, high-density lipoprotein cholesterol, non-high-molecular-weight adiponectin and soluble leptin receptor, which in combination explained 46% (95% CI 37–57%) of the association in men and 50% (95% CI 40–65%) of the association in women. Similar results were observed for the associations with BMI in men. These data suggest that alterations in levels of these metabolic biomarkers may represent a primary mechanism of action in the relation of adiposity with colon cancer. Further studies are warranted to determine whether altering their concentrations may reduce colon cancer risk.
Abstract
What's new?
Adiposity is a well-established risk factor for colon cancer. However, the mechanisms that underlie this relationship still aren't well understood. In this study, the authors evaluated a panel of inflammatory and metabolic biomarkers for their impact on colon-cancer risk. They found that serum levels of high-density lipoprotein cholesterol, non-high-molecular-weight adiponectin, and soluble leptin receptor had the greatest impact on the association between adiposity and colon cancer. These biomarkers may thus lead to promising strategies for the targeted prevention of colon cancer.
Supporting Information
Additional Supporting Information may be found in the online version of this article.
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