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 Aleksandrova, 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 DossusAntoine 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

Research output: Contribution to journalArticlepeer-review

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 multi-variable-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.

Original languageEnglish
Pages (from-to)261-275
Number of pages15
JournalEuropean Journal of Epidemiology
Volume29
Issue number4
DOIs
Publication statusPublished - 2014

Keywords

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

ASJC Scopus subject areas

  • Epidemiology

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