Association of CRP genetic variants with blood concentrations of C‐reactive protein and colorectal cancer risk
Year: 2014
Type: article
Study design: Observational Study
Abstract: High blood concentrations of C-reactive protein (CRP) have been associated with elevated risk of colorectal cancer in several prospective studies including the European Prospective Investigation into Cancer and Nutrition (EPIC), but it is unknown whether these observations reflect a causal relationship. We aimed to investigate whether CRP genetic variants associated with lifelong higher CRP concentrations translate into higher colorectal cancer risk. We conducted a prospective nested case-control study within EPIC including 727 cases diagnosed between 1992 and 2003 and 727 matched controls selected according to an incidence-density sampling protocol. Baseline CRP concentrations were measured in plasma samples by a high sensitivity assay. Tagging single nucleotide polymorphisms (SNPs) in the CRP gene (rs1205, rs1800947, rs1130864, rs2808630, rs3093077) were identified via HapMap. The causal effect of CRP on colorectal cancer risk was examined in a Mendelian Randomization approach utilizing multiple CRP genetic variants as instrumental variables. The SNPs rs1205, rs1800947, rs1130864 and rs3093077 were significantly associated with CRP concentrations and were incorporated in a CRP allele score which was associated with 13% higher CRP concentrations per allele count (95% confidence interval 8-19%). Using the CRP-score as instrumental variable, genetically twofold higher CRP concentrations were associated with higher risk of colorectal cancer (odds ratio 1.74, 95% confidence interval 1.06-2.85). Similar observations were made using alternative definitions of instrumental variables. Our findings give support to the hypothesis that elevated circulating CRP may play a direct role in the etiology of colorectal cancer.
Source: International Journal of Cancer
DOI: 10.1002/ijc.29086
Authors: Katharina Nimptsch, Krasimira Aleksandrova, Heiner Boeing, Jürgen Janke, Young‐Ae Lee, Mazda Jenab, H.B(as) Bueno‐de‐Mesquita, Eugène HJM Jansen, Konstantinos K Tsilidis, Antonia Trichopoulou, Elisabete Weiderpass, Chunsen Wu, Kim Overvad, Anne Tjønneland, Marie‐Christine Boutron‐Ruault, Laure Dossus, Antoine Racine, Rudolf Kaaks, Federico Canzian, Pagona Lagiou, Dimitrios Trichopoulos, Domenico Palli, Claudia Agnoli, Rosario Tumino, Paolo Vineis, Salvatore Panico, Anders Johansson, Bethany Van Guelpen, Kay‐Tee Khaw, Nick Wareham, Petra H Peeters, J. Ramón Quirós, Adoración Venceslá García, Esther Molina‐Montes, Miren Dorronsoro, María‐Dolores Chirlaque, Aurelio Barricarte Gurrea, Timothy J Key, Talita Duarte‐Salles, Magdalena Stepien, Marc J. Gunter, Elio Riboli, Tobias Pischon
Institutions: Harvard University, Max Delbrück Center, German Institute of Human Nutrition, Centre international de recherche sur le cancer, University Medical Center Utrecht, University of Malaya, National Institute for Public Health and the Environment, Imperial College London, University of Ioannina, University of Oxford, National and Kapodistrian University of Athens, Hellenic Health Foundation, Karolinska Institutet, Cancer Registry of Norway, Folkhälsans Forskningscentrum, UiT The Arctic University of Norway, Aarhus University, Danish Cancer Society, Université Paris-Sud, Inserm, Institut Gustave Roussy, Centre de recherche en Epidémiologie et Santé des Populations, German Cancer Research Center, Academy of Athens, Istituto per lo Studio e la Prevenzione Oncologica, Fondazione IRCCS Istituto Nazionale dei Tumori, Azienda Usl 8 Arezzo, Italian institute for Genomic Medicine, Federico II University Hospital, University of Naples Federico II, Umeå University, University of Cambridge, Addenbrooke's Hospital, Medical Research Council, Gobierno del Principado de Asturias, Institut d'Investigació Biomédica de Bellvitge, Institut Català d'Oncologia, Universidad de Granada, Instituto de Investigación Biosanitaria de Granada, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Andalusian School of Public Health, Biogipuzkoa Health Research Institute, Servicio Murciano de Salud
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
Funders: Kræftens Bekæmpelse, Deutsches Krebsforschungszentrum, Centre International de Recherche sur le Cancer, Cancer Research UK, National Institute for Health and Care Research, European Commission, Institut National de la Santé et de la Recherche Médicale, Bundesministerium für Bildung und Forschung, Cancerfonden, Ministerie van Volksgezondheid, Welzijn en Sport, Ligue Contre le Cancer, NordForsk, Associazione Italiana per la Ricerca sul Cancro, Deutsche Krebshilfe, Institut Gustave-Roussy, Mutuelle Générale de l'Education Nationale, Hellenic Health Foundation, Medical Research Council, World Cancer Research Fund, Instituto de Salud Carlos III, Health and Medical Research Fund
OpenAlex ID: W2115418403