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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Item Type:	Article
Title:	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)
Creators Name:	Aleksandrova, K., Jenab, M., Bueno-de-Mesquita, H.B., Fedirko, V., Kaaks, R., Lukanova, A., van Duijnhoven, F.J.B., Jansen, E., Rinaldi, S., Romieu, I., Ferrari, P., Murphy, N., Gunter, M.J., Riboli, E., Westhpal, S., Overvad, K., Tjønneland, A., Halkjær, J., Boutron-Ruault, M.C., Dossus, L., Racine, A., Trichopoulou, A., Bamia, C., Orfanos, P., Agnoli, C., Palli, D., Panico, S., Tumino, R., Vineis, P., Peeters, P.H., Duell, E.J., Molina-Montes, E., Quirós, J.R., Dorronsoro, M., Chirlaque, M.D., Barricarte, A., Ljuslinder, I., Palmqvist, R., Travis, R.C., Khaw, K.T., Wareham, N., Pischon, T. and Boeing, H.
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)
Source:	European Journal of Epidemiology
ISSN:	0393-2990
Publisher:	Springer
Volume:	29
Number:	4
Page Range:	261-275
Date:	1 April 2014
Official Publication:	https://doi.org/10.1007/s10654-014-9901-8
PubMed:	View item in PubMed

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