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Biomarker patterns of inflammatory and metabolic pathways are associated with risk of colorectal cancer: results from the European Prospective Investigation into Cancer and Nutrition (EPIC)

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Abstract

A number of biomarkers of inflammatory and metabolic pathways are individually related to higher risk of colorectal cancer (CRC); however, the association between biomarker patterns and CRC incidence has not been previously evaluated. Our study investigates the association of biomarker patterns with CRC in a prospective nested case–control study within the European Prospective Investigation into Cancer and Nutrition (EPIC). During median follow-up time of 7.0 (3.7–9.4) years, 1,260 incident CRC cases occurred and were matched to 1,260 controls using risk-set sampling. Pre-diagnostic measurements of C-peptide, glycated hemoglobin, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), C-reactive protein (CRP), reactive oxygen metabolites (ROM), insulin-like growth factor 1, adiponectin, leptin and soluble leptin receptor (sOB-R) were used to derive biomarker patterns from principal component analysis (PCA). The relation with CRC incidence was assessed using conditional logistic regression models. We identified four biomarker patterns ‘HDL-C/Adiponectin fractions’, ‘ROM/CRP’, ‘TG/C-peptide’ and ‘leptin/sOB-R’ to explain 60 % of the overall biomarker variance. In multivariable-adjusted logistic regression, the ‘HDL-C/Adiponectin fractions’, ‘ROM/CRP’ and ‘leptin/sOB-R’ patterns were associated with CRC risk [for the highest quartile vs the lowest, incidence rate ratio (IRR) = 0.69, 95 % CI 0.51–0.93, P-trend = 0.01; IRR = 1.70, 95 % CI 1.30–2.23, P-trend = 0.002; and IRR = 0.79, 95 % CI 0.58–1.07; P-trend = 0.05, respectively]. In contrast, the ‘TG/C-peptide’ pattern was not associated with CRC risk (IRR = 0.75, 95 % CI 0.56–1.00, P-trend = 0.24). After cases within the first 2 follow-up years were excluded, the ‘ROM/CRP’ pattern was no longer associated with CRC risk, suggesting potential influence of preclinical disease on these associations. By application of PCA, the study identified ‘HDL-C/Adiponectin fractions’, ‘ROM/CRP’ and ‘leptin/sOB-R’ as biomarker patterns representing potentially important pathways for CRC development.

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Acknowledgments

This work has been supported by World Cancer Research Fund International and Wereld Kanker Onderzoek Fonds (WCRF NL). The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); Hellenic Health Foundation (Greece); Italian Association for Research on Cancer (AIRC) and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Scientific Council and Regional Government of Skåne and Västerbotten (Sweden); Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, and Wellcome Trust (United Kingdom). The funding sources had no influence on the design of the study; the collection, analysis, and interpretation of data; the writing of the report; or the decision to submit the paper for publication. The authors thank all EPIC participants and staff for their outstanding contribution to the study.

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Authors and Affiliations

  1. Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert Allee 114-116, 14558, Nuthetal, Germany

    Krasimira Aleksandrova & Heiner Boeing

  2. International Agency for Research on Cancer (IARC-WHO), Lyon, France

    Mazda Jenab, Veronika Fedirko, Sabina Rinaldi, Isabelle Romieu & Pietro Ferrari

  3. National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands

    H. Bas Bueno-de-Mesquita, Fränzel J. B. van Duijnhoven & Eugene Jansen

  4. Department of Gastroenterology and Hepatology, University Medical Center, Utrecht, The Netherlands

    H. Bas Bueno-de-Mesquita

  5. Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA

    Veronika Fedirko

  6. Winship Cancer Institute, Emory University, Atlanta, GA, USA

    Veronika Fedirko

  7. Division of Cancer Epidemiology, German Cancer Research Centre, Heidelberg, Germany

    Rudolf Kaaks & Annekatrin Lukanova

  8. Department of Medical Biosciences/Pathology, University of Umeå, Umeå, Sweden

    Annekatrin Lukanova

  9. Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands

    Fränzel J. B. van Duijnhoven

  10. Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK

    Neil Murphy, Marc J. Gunter, Elio Riboli, Paolo Vineis & Petra H. Peeters

  11. Institute of Clinical Chemistry, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany

    Sabine Westhpal

  12. Department of Epidemiology, School of Public Health, Aarhus University, Aarhus, Denmark

    Kim Overvad

  13. Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark

    Anne Tjønneland & Jytte Halkjær

  14. Inserm, Centre for Research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women’s Health Team, 94805, Villejuif, France

    Marie-Christine Boutron-Ruault, Laure Dossus & Antoine Racine

  15. UMRS 1018, Univ Paris Sud, 94805, Villejuif, France

    Marie-Christine Boutron-Ruault, Laure Dossus & Antoine Racine

  16. IGR, 94805, Villejuif, France

    Marie-Christine Boutron-Ruault, Laure Dossus & Antoine Racine

  17. Hellenic Health Foundation, Athens, Greece

    Antonia Trichopoulou

  18. WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece

    Antonia Trichopoulou, Christina Bamia & Philippos Orfanos

  19. Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy

    Claudia Agnoli

  20. Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy

    Domenico Palli

  21. Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy

    Salvatore Panico

  22. Cancer Registry and Histopathology Unit, “M.P.Arezzo” Hospital, Ragusa, Italy

    Rosario Tumino

  23. HuGeF Foundation, Turin, Italy

    Paolo Vineis

  24. Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands

    Petra H. Peeters

  25. Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Bellvitge Biomedical Research Institute (IDIBELL), Catalan Institute of Oncology (ICO), Barcelona, Spain

    Eric J. Duell

  26. Escuela Andaluza de Salud Pública, Granada, Spain

    Esther Molina-Montes

  27. CIBER Epidemiology and Public Health CIBERESP, Spain http://www.ciberesp.es/

    Esther Molina-Montes & Maria-Dolores Chirlaque

  28. Instituto de Investigación Biosanitaria de Granada (Granada.bs), Granada, Spain

    Esther Molina-Montes

  29. Public Health Directorate, Asturias, Spain

    J. Ramón Quirós

  30. Epidemiology and Health Information, Public Health Division of Gipuzkoa, Basque Regional Health Department, San Sebastian, Spain

    Miren Dorronsoro

  31. Department of Epidemiology, Murcia Regional Health Authority, Murcia, Spain

    Maria-Dolores Chirlaque

  32. Navarre Public Health Institute, Pamplona, Spain

    Aurelio Barricarte

  33. Department of Radiation Sciences, Umeå University Hospital, Umeå, Sweden

    Ingrid Ljuslinder

  34. Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden

    Richard Palmqvist

  35. Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK

    Ruth C. Travis

  36. Clinical Gerontology Unit, Addenbrooke’s Hospital, University of Cambridge School of Clinical Medicine, Cambridge, UK

    Kay-Tee Khaw

  37. MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine , Cambridge, UK

    Nicholas Wareham

  38. Molecular Epidemiology Group, Max Delbrueck Center for Molecular Medicine (MDC), Berlin-Buch, Germany

    Tobias Pischon

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  1. Krasimira Aleksandrova
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  2. Mazda Jenab
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  8. Eugene Jansen
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  9. Sabina Rinaldi
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  10. Isabelle Romieu
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  11. Pietro Ferrari
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  12. Neil Murphy
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  13. Marc J. Gunter
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  15. Sabine Westhpal
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  19. Marie-Christine Boutron-Ruault
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Corresponding author

Correspondence to Krasimira Aleksandrova.

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Aleksandrova, K., Jenab, M., Bueno-de-Mesquita, H.B. et al. Biomarker patterns of inflammatory and metabolic pathways are associated with risk of colorectal cancer: results from the European Prospective Investigation into Cancer and Nutrition (EPIC). Eur J Epidemiol 29, 261–275 (2014). https://doi.org/10.1007/s10654-014-9901-8

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  • DOI: https://doi.org/10.1007/s10654-014-9901-8

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