期刊
EUROPEAN JOURNAL OF EPIDEMIOLOGY
卷 29, 期 4, 页码 261-275出版社
SPRINGER
DOI: 10.1007/s10654-014-9901-8
关键词
Colorectal cancer; Biomarker patterns; Inflammatory and metabolic pathways; Principal component analysis; European Prospective Investigation into Cancer and Nutrition (EPIC)
资金
- World Cancer Research Fund International and Wereld Kanker Onderzoek Fonds (WCRF NL)
- European Commission (DG-SANCO)
- International Agency for Research on Cancer
- Danish Cancer Society (Denmark)
- Ligue contre le Cancer (France)
- Institut Gustave Roussy (France)
- Mutuelle Generale de l'Education Nationale (France)
- Institut National de la Sante et de la Recherche Medicale (INSERM) (France)
- Deutsche Krebshilfe (Germany)
- Deutsches Krebsforschungszentrum (Germany)
- Federal Ministry of Education and Research (Germany)
- Hellenic Health Foundation (Greece)
- Italian Association for Research on Cancer (AIRC) (Italy)
- National Research Council (Italy)
- Dutch Ministry of Public Health, Welfare and Sports (VWS) (The Netherlands)
- Netherlands Cancer Registry (NKR) (The Netherlands)
- LK Research Funds (The Netherlands)
- Dutch Prevention Funds (The Netherlands)
- Dutch ZON (Zorg Onderzoek Nederland) (The Netherlands)
- World Cancer Research Fund (WCRF) (The Netherlands)
- Statistics Netherlands (The Netherlands)
- Health Research Fund (FIS) (Spain)
- Regional Governments of Andalucia (Spain)
- Asturias (Spain)
- Basque Country (Spain)
- Murcia and Navarra (Spain)
- ISCIII RETIC (Spain) [RD06/0020]
- Swedish Cancer Society (Sweden)
- Swedish Scientific Council (Sweden)
- Regional Government of Skane and Vasterbotten (Sweden)
- Cancer Research UK (United Kingdom)
- Medical Research Council (United Kingdom)
- Stroke Association (United Kingdom)
- British Heart Foundation (United Kingdom)
- Department of Health, Food Standards Agency (United Kingdom)
- Wellcome Trust (United Kingdom)
- Cancer Research UK [16491, 14136] Funding Source: researchfish
- Medical Research Council [MC_U106179471, G0401527, MC_UU_12015/1, G1000143] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0512-10114, NF-SI-0512-10135] Funding Source: researchfish
- MRC [MC_UU_12015/1] Funding Source: UKRI
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.
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