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European Journal of Epidemiology

, Volume 29, Issue 4, pp 261–275 | Cite as

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)

  • Krasimira AleksandrovaEmail author
  • Mazda Jenab
  • H. Bas Bueno-de-Mesquita
  • Veronika Fedirko
  • Rudolf Kaaks
  • Annekatrin Lukanova
  • Fränzel J. B. van Duijnhoven
  • Eugene Jansen
  • Sabina Rinaldi
  • Isabelle Romieu
  • Pietro Ferrari
  • Neil Murphy
  • Marc J. Gunter
  • Elio Riboli
  • Sabine Westhpal
  • Kim Overvad
  • Anne Tjønneland
  • Jytte Halkjær
  • Marie-Christine Boutron-Ruault
  • Laure Dossus
  • Antoine Racine
  • Antonia Trichopoulou
  • Christina Bamia
  • Philippos Orfanos
  • Claudia Agnoli
  • Domenico Palli
  • Salvatore Panico
  • Rosario Tumino
  • Paolo Vineis
  • Petra H. Peeters
  • Eric J. Duell
  • Esther Molina-Montes
  • J. Ramón Quirós
  • Miren Dorronsoro
  • Maria-Dolores Chirlaque
  • Aurelio Barricarte
  • Ingrid Ljuslinder
  • Richard Palmqvist
  • Ruth C. Travis
  • Kay-Tee Khaw
  • Nicholas Wareham
  • Tobias Pischon
  • Heiner Boeing
CANCER

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.

Keywords

Colorectal cancer Biomarker patterns Inflammatory and metabolic pathways Principal component analysis European Prospective Investigation into Cancer and Nutrition (EPIC) 

Notes

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.

Supplementary material

10654_2014_9901_MOESM1_ESM.docx (36 kb)
Supplementary material 1 (DOCX 35 kb)

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Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Krasimira Aleksandrova
    • 1
    Email author
  • Mazda Jenab
    • 2
  • H. Bas Bueno-de-Mesquita
    • 3
    • 4
  • Veronika Fedirko
    • 2
    • 5
    • 6
  • Rudolf Kaaks
    • 7
  • Annekatrin Lukanova
    • 7
    • 8
  • Fränzel J. B. van Duijnhoven
    • 3
    • 9
  • Eugene Jansen
    • 3
  • Sabina Rinaldi
    • 2
  • Isabelle Romieu
    • 2
  • Pietro Ferrari
    • 2
  • Neil Murphy
    • 10
  • Marc J. Gunter
    • 10
  • Elio Riboli
    • 10
  • Sabine Westhpal
    • 11
  • Kim Overvad
    • 12
  • Anne Tjønneland
    • 13
  • Jytte Halkjær
    • 13
  • Marie-Christine Boutron-Ruault
    • 14
    • 15
    • 16
  • Laure Dossus
    • 14
    • 15
    • 16
  • Antoine Racine
    • 14
    • 15
    • 16
  • Antonia Trichopoulou
    • 17
    • 18
  • Christina Bamia
    • 18
  • Philippos Orfanos
    • 18
  • Claudia Agnoli
    • 19
  • Domenico Palli
    • 20
  • Salvatore Panico
    • 21
  • Rosario Tumino
    • 22
  • Paolo Vineis
    • 10
    • 23
  • Petra H. Peeters
    • 10
    • 24
  • Eric J. Duell
    • 25
  • Esther Molina-Montes
    • 26
    • 27
    • 28
  • J. Ramón Quirós
    • 29
  • Miren Dorronsoro
    • 30
  • Maria-Dolores Chirlaque
    • 27
    • 31
  • Aurelio Barricarte
    • 32
  • Ingrid Ljuslinder
    • 33
  • Richard Palmqvist
    • 34
  • Ruth C. Travis
    • 35
  • Kay-Tee Khaw
    • 36
  • Nicholas Wareham
    • 37
  • Tobias Pischon
    • 38
  • Heiner Boeing
    • 1
  1. 1.Department of EpidemiologyGerman Institute of Human Nutrition Potsdam-RehbrueckeNuthetalGermany
  2. 2.International Agency for Research on Cancer (IARC-WHO)LyonFrance
  3. 3.National Institute for Public Health and the Environment (RIVM)BilthovenThe Netherlands
  4. 4.Department of Gastroenterology and HepatologyUniversity Medical CenterUtrechtThe Netherlands
  5. 5.Department of Epidemiology, Rollins School of Public HealthEmory UniversityAtlantaUSA
  6. 6.Winship Cancer InstituteEmory UniversityAtlantaUSA
  7. 7.Division of Cancer EpidemiologyGerman Cancer Research CentreHeidelbergGermany
  8. 8.Department of Medical Biosciences/PathologyUniversity of UmeåUmeåSweden
  9. 9.Division of Human NutritionWageningen UniversityWageningenThe Netherlands
  10. 10.Department of Epidemiology and Biostatistics, School of Public HealthImperial College LondonLondonUK
  11. 11.Institute of Clinical ChemistryOtto-von-Guericke-University MagdeburgMagdeburgGermany
  12. 12.Department of Epidemiology, School of Public HealthAarhus UniversityAarhusDenmark
  13. 13.Diet, Genes and EnvironmentDanish Cancer Society Research CenterCopenhagenDenmark
  14. 14.Inserm, Centre for Research in Epidemiology and Population Health (CESP), U1018Nutrition, Hormones and Women’s Health TeamVillejuifFrance
  15. 15.UMRS 1018Univ Paris SudVillejuifFrance
  16. 16.IGRVillejuifFrance
  17. 17.Hellenic Health FoundationAthensGreece
  18. 18.WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical StatisticsUniversity of Athens Medical SchoolAthensGreece
  19. 19.Nutritional Epidemiology UnitFondazione IRCCS Istituto Nazionale TumoriMilanItaly
  20. 20.Molecular and Nutritional Epidemiology UnitCancer Research and Prevention Institute (ISPO)FlorenceItaly
  21. 21.Department of Clinical and Experimental MedicineFederico II UniversityNaplesItaly
  22. 22.Cancer Registry and Histopathology Unit“M.P.Arezzo” HospitalRagusaItaly
  23. 23.HuGeF FoundationTurinItaly
  24. 24.Julius Center for Health Sciences and Primary CareUniversity Medical CenterUtrechtThe Netherlands
  25. 25.Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Bellvitge Biomedical Research Institute (IDIBELL)Catalan Institute of Oncology (ICO)BarcelonaSpain
  26. 26.Escuela Andaluza de Salud PúblicaGranadaSpain
  27. 27.CIBER Epidemiology and Public Health CIBERESP, Spain
  28. 28.Instituto de Investigación Biosanitaria de Granada (Granada.bs)GranadaSpain
  29. 29.Public Health DirectorateAsturiasSpain
  30. 30.Epidemiology and Health Information, Public Health Division of GipuzkoaBasque Regional Health DepartmentSan SebastianSpain
  31. 31.Department of EpidemiologyMurcia Regional Health AuthorityMurciaSpain
  32. 32.Navarre Public Health InstitutePamplonaSpain
  33. 33.Department of Radiation SciencesUmeå University HospitalUmeåSweden
  34. 34.Department of Medical Biosciences, PathologyUmeå UniversityUmeåSweden
  35. 35.Cancer Epidemiology Unit, Nuffield Department of Clinical MedicineUniversity of OxfordOxfordUK
  36. 36.Clinical Gerontology Unit, Addenbrooke’s HospitalUniversity of Cambridge School of Clinical MedicineCambridgeUK
  37. 37.MRC Epidemiology Unit, Institute of Metabolic ScienceUniversity of Cambridge School of Clinical Medicine CambridgeUK
  38. 38.Molecular Epidemiology GroupMax Delbrueck Center for Molecular Medicine (MDC)Berlin-BuchGermany

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