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 journalArticle

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

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Metabolic Networks and Pathways
Colorectal Neoplasms
Biomarkers
Leptin Receptors
C-Reactive Protein
Adiponectin
Leptin
Neoplasms
HDL Cholesterol
Oxygen
C-Peptide
Incidence
Triglycerides
Logistic Models
Principal Component Analysis
Glycosylated Hemoglobin A
Somatomedins
Protein C
Case-Control Studies

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

Cite this

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

In: European Journal of Epidemiology, Vol. 29, No. 4, 2014, p. 261-275.

Research output: Contribution to journalArticle

Aleksandrova, K, Jenab, M, Bueno-de-Mesquita, HB, Fedirko, V, Kaaks, R, Lukanova, A, Van Duijnhoven, FJB, Jansen, E, Rinaldi, S, Romieu, I, Ferrari, P, Murphy, N, Gunter, MJ, Riboli, E, Westhpal, S, Overvad, K, Tjønneland, A, Halkjær, J, Boutron-Ruault, MC, Dossus, L, Racine, A, Trichopoulou, A, Bamia, C, Orfanos, P, Agnoli, C, Palli, D, Panico, S, Tumino, R, Vineis, P, Peeters, PH, Duell, EJ, Molina-Montes, E, Quirós, JR, Dorronsoro, M, Chirlaque, MD, Barricarte, A, Ljuslinder, I, Palmqvist, R, Travis, RC, Khaw, KT, Wareham, N, Pischon, T & Boeing, H 2014, '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)', European Journal of Epidemiology, vol. 29, no. 4, pp. 261-275. https://doi.org/10.1007/s10654-014-9901-8
Aleksandrova, Krasimira ; Jenab, Mazda ; Bueno-de-Mesquita, H. Bas ; Fedirko, Veronika ; Kaaks, Rudolf ; Lukanova, Annekatrin ; Van Duijnhoven, Fränzel J B ; Jansen, Eugene ; Rinaldi, Sabina ; Romieu, Isabelle ; Ferrari, Pietro ; Murphy, Neil ; Gunter, Marc J. ; Riboli, Elio ; Westhpal, Sabine ; Overvad, Kim ; Tjønneland, Anne ; Halkjær, Jytte ; Boutron-Ruault, Marie Christine ; Dossus, Laure ; Racine, Antoine ; Trichopoulou, Antonia ; Bamia, Christina ; Orfanos, Philippos ; Agnoli, Claudia ; Palli, Domenico ; Panico, Salvatore ; Tumino, Rosario ; Vineis, Paolo ; Peeters, Petra H. ; Duell, Eric J. ; Molina-Montes, Esther ; Quirós, J. Ramón ; Dorronsoro, Miren ; Chirlaque, Maria Dolores ; Barricarte, Aurelio ; Ljuslinder, Ingrid ; Palmqvist, Richard ; Travis, Ruth C. ; Khaw, Kay Tee ; Wareham, Nicholas ; Pischon, Tobias ; Boeing, Heiner. / 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). In: European Journal of Epidemiology. 2014 ; Vol. 29, No. 4. pp. 261-275.
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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 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.",
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T1 - Biomarker patterns of inflammatory and metabolic pathways are associated with risk of colorectal cancer

T2 - Results from the European Prospective Investigation into Cancer and Nutrition (EPIC)

AU - Aleksandrova, Krasimira

AU - Jenab, Mazda

AU - Bueno-de-Mesquita, H. Bas

AU - Fedirko, Veronika

AU - Kaaks, Rudolf

AU - Lukanova, Annekatrin

AU - Van Duijnhoven, Fränzel J B

AU - Jansen, Eugene

AU - Rinaldi, Sabina

AU - Romieu, Isabelle

AU - Ferrari, Pietro

AU - Murphy, Neil

AU - Gunter, Marc J.

AU - Riboli, Elio

AU - Westhpal, Sabine

AU - Overvad, Kim

AU - Tjønneland, Anne

AU - Halkjær, Jytte

AU - Boutron-Ruault, Marie Christine

AU - Dossus, Laure

AU - Racine, Antoine

AU - Trichopoulou, Antonia

AU - Bamia, Christina

AU - Orfanos, Philippos

AU - Agnoli, Claudia

AU - Palli, Domenico

AU - Panico, Salvatore

AU - Tumino, Rosario

AU - Vineis, Paolo

AU - Peeters, Petra H.

AU - Duell, Eric J.

AU - Molina-Montes, Esther

AU - Quirós, J. Ramón

AU - Dorronsoro, Miren

AU - Chirlaque, Maria Dolores

AU - Barricarte, Aurelio

AU - Ljuslinder, Ingrid

AU - Palmqvist, Richard

AU - Travis, Ruth C.

AU - Khaw, Kay Tee

AU - Wareham, Nicholas

AU - Pischon, Tobias

AU - Boeing, Heiner

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - Biomarker patterns

KW - Colorectal cancer

KW - European Prospective Investigation into Cancer and Nutrition (EPIC)

KW - Inflammatory and metabolic pathways

KW - Principal component analysis

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