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 language | English |
|---|---|
| Pages (from-to) | 261-275 |
| Number of pages | 15 |
| Journal | European Journal of Epidemiology |
| Volume | 29 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2014 |
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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 journal › Article
}
TY - JOUR
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
UR - http://www.scopus.com/inward/record.url?scp=84903769474&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84903769474&partnerID=8YFLogxK
U2 - 10.1007/s10654-014-9901-8
DO - 10.1007/s10654-014-9901-8
M3 - Article
C2 - 24791703
AN - SCOPUS:84903769474
VL - 29
SP - 261
EP - 275
JO - European Journal of Epidemiology
JF - European Journal of Epidemiology
SN - 0393-2990
IS - 4
ER -