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Title: | Circulating Levels of Insulin-like Growth Factor 1 and Insulin-like Growth Factor Binding Protein 3 Associate With Risk of Colorectal Cancer Based on Serologic and Mendelian Randomization Analyses. | Authors: | English D.;Van Guelpen B.;Visvanathan K.;Vodicka P.;Vodickova L.;Vymetalkova V.;Wang H.;White E.;Wolk A.;Woods M.O.;Wu A.H.;Zheng W.;Peters U.;Gunter M.J.;Murphy N.;Carreras-Torres R.;Song M.;Chan A.T.;Martin R.M.;Papadimitriou N.;Dimou N.;Tsilidis K.K.;Banbury B.;Bradbury K.E.;Besevic J.;Rinaldi S.;Riboli E.;Cross A.J.;Travis R.C.;Agnoli C.;Albanes D.;Berndt S.I.;Bezieau S.;Bishop D.T.;Brenner H.;Buchanan D.D.;Onland-Moret N.C.;Burnett-Hartman A.;Campbell P.T.;Casey G.;Castellvi-Bel S.;Chang-Claude J.;Chirlaque M.-D.;de la Chapelle A.;Figueiredo J.C.;Gallinger S.J.;Giles G.G.;Gruber S.B.;Gsur A.;Hampe J.;Hampel H.;Harrison T.A.;Hoffmeister M.;Hsu L.;Huang W.-Y.;Huyghe J.R.;Jenkins M.A.;Keku T.O.;Kuhn T.;Kweon S.-S.;Le Marchand L.;Li C.I.;Li L.;Lindblom A.;Martin V.;Milne R.L.;Moreno V.;Newcomb P.A.;Offit K.;Ogino S.;Ose J.;Perduca V.;Phipps A.I.;Platz E.A.;Potter J.D.;Qu C.;Rennert G.;Sakoda L.C.;Schafmayer C.;Schoen R.E.;Slattery M.L.;Tangen C.M.;Ulrich C.M.;van Duijnhoven F.J.B. | Monash Health Department(s): | Monash University - School of Clinical Sciences at Monash Health | Institution: | (Murphy, Papadimitriou, Dimou, Rinaldi, Gunter) Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France (Carreras-Torres, Moreno) Colorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain (Song, Chan) Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States (Song, Chan) Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States (Song, Ogino) Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, United States (Song) Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, United States (Chan) Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States (Martin) MRC Integrative Epidemiology Unit (IEU), Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom (Martin) Bristol Medical School, Department of Population Health Sciences, University of Bristol, Bristol, United Kingdom (Martin) National Institute for Health Research (NIHR) Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and the University of Bristol, Bristol, United Kingdom (Tsilidis) Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece (Tsilidis, Besevic, Riboli, Cross) Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom (Banbury, Harrison, Hsu, Huyghe, Li, Newcomb, Phipps, Potter, Qu, Sakoda, White, Peters) Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States (Bradbury) National Institute for Health Innovation, School of Population Health, The University of Auckland, Auckland, New Zealand (Travis) Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom (Agnoli) Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy (Albanes, Berndt, Huang) Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States (Bezieau) Service de Genetique Medicale, Centre Hospitalier Universitaire (CHU) Nantes, Nantes, France (Bishop) Institute of Medical Research at St. James's, University of Leeds, Leeds, United Kingdom (Brenner, Hoffmeister) Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany (Brenner) Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany (Brenner) German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany (Buchanan) Colorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, Parkville, Victoria 3010, Australia (Buchanan) University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, Victoria 3010, Australia (Buchanan) Genetic Medicine and Family Cancer Clinic, The Royal Melbourne Hospital, Parkville, Victoria, Australia (Onland-Moret) Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands (Burnett-Hartman) Institute for Health Research, Kaiser Permanente Colorado, Denver, CO, United States (Campbell) Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia, Georgia (Casey) Center for Public Health Genomics, University of Virginia, Charlottesville, VA, United States (Castellvi-Bel) Gastroenterology Department, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Hospital Clinic, Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain (Chang-Claude, Kuhn) Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany (Chirlaque) Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia University, Murcia, Spain (Chirlaque, Martin, Moreno) CIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain (de la Chapelle) Department of Cancer Biology and Genetics and the Comprehensive Cancer Center, The Ohio State University, Columbus, OH, United States (English, Giles, Milne) Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia (English, Giles, Jenkins, Milne) Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia (Figueiredo) Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States (Gallinger) Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (Giles, Milne) Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia (Gruber) Department of Preventive Medicine & USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States (Gsur) Institute of Cancer Research, Department of Medicine I, Medical University Vienna, Vienna, Austria (Hampe) Department of Medicine I, University Hospital Dresden, Technische Universitat Dresden (TU Dresden), Dresden, Germany (Hampel) Division of Human Genetics, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH, United States (Hsu) Department of Biostatistics, University of Washington, Seattle, WA, United States (Keku) Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, United States (Kweon) Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, Korea, South Korea (Kweon) Jeonnam Regional Cancer Center, Chonnam National University Hwasun Hospital, Hwasun, Korea, South Korea (Le Marchand, Wang) University of Hawaii Cancer Center, Honolulu, HI, United States (Li) Department of Family Medicine, University of Virginia, Charlottesville, VA, United States (Lindblom) Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden (Lindblom) Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden (Martin) Biomedicine Institute (IBIOMED), University of Leon, Leon, Spain (Moreno) Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain (Newcomb) School of Public Health, University of Washington, Seattle, WA, United States (Offit) Clinical Genetics Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, United States (Offit) Department of Medicine, Weill Cornell Medical College, New York, NY, United States (Ogino) Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States (Ogino) Cancer Immunology and Cancer Epidemiology Programs, Dana-Farber Harvard Cancer Center, Boston, MA, United States (Ogino) Broad Institute of MIT and Harvard, Cambridge, MA, United States (Ose, Ulrich) Huntsman Cancer Institute and Department of Population Health Sciences, University of Utah, Salt Lake City, UT, United States (Perduca) CESP (Inserm U1018), Fac. de medecine - Universite Paris-Saclay, Fac. de medecine - UVSQ, Villejuif 94805, France (Perduca) Gustave Roussy, Villejuif F-94805, France (Perduca) Laboratoire de Mathematiques Appliquees MAP5 (UMR CNRS 8145), Universite Paris Descartes, France (Phipps, White, Peters) Department of Epidemiology, University of Washington, Seattle, WA, United States (Platz, Visvanathan) Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States (Potter) Centre for Public Health Research, Massey University, Wellington, New Zealand (Rennert) Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa, Israel (Rennert) Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel (Sakoda) Division of Research, Kaiser Permanente Northern California, Oakland, CA, United States (Schafmayer) Department of General and Thoracic Surgery, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany (Schoen) Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA, United States (Slattery) Department of Internal Medicine, University of Utah, Salt Lake City, UT, United States (Tangen) SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, United States (van Duijnhoven) Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, Netherlands (Van Guelpen) Department of Radiation Sciences, Oncology Unit, Umea University, Umea, Sweden (Van Guelpen) Wallenberg Centre for Molecular Medicine, Umea University, Umea, Sweden (Vodicka, Vodickova, Vymetalkova) Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czechia (Vodicka, Vodickova, Vymetalkova) Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czechia (Vodicka, Vodickova, Vymetalkova) Faculty of Medicine and Biomedical Center in Pilsen, Charles University, Pilsen, Czechia (Wolk) Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden (Woods) Memorial University of Newfoundland, Discipline of Genetics, St. John's, Canada (Wu) University of Southern California, Preventive Medicine, Los Angeles, CA, United States (Zheng) Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, TN, United States | Issue Date: | 1-Apr-2020 | Copyright year: | 2020 | Publisher: | W.B. Saunders | Place of publication: | United States | Publication information: | Gastroenterology. 158 (5) (pp 1300-1312.e20), 2020. Date of Publication: April 2020. | Journal: | Gastroenterology | Abstract: | Background & Aims: Human studies examining associations between circulating levels of insulin-like growth factor 1 (IGF1) and insulin-like growth factor binding protein 3 (IGFBP3) and colorectal cancer risk have reported inconsistent results. We conducted complementary serologic and Mendelian randomization (MR) analyses to determine whether alterations in circulating levels of IGF1 or IGFBP3 are associated with colorectal cancer development. Method(s): Serum levels of IGF1 were measured in blood samples collected from 397,380 participants from the UK Biobank, from 2006 through 2010. Incident cancer cases and cancer cases recorded first in death certificates were identified through linkage to national cancer and death registries. Complete follow-up was available through March 31, 2016. For the MR analyses, we identified genetic variants associated with circulating levels of IGF1 and IGFBP3. The association of these genetic variants with colorectal cancer was examined with 2-sample MR methods using genome-wide association study consortia data (52,865 cases with colorectal cancer and 46,287 individuals without [controls]) Results: After a median follow-up period of 7.1 years, 2665 cases of colorectal cancer were recorded. In a multivariable-adjusted model, circulating level of IGF1 associated with colorectal cancer risk (hazard ratio per 1 standard deviation increment of IGF1, 1.11; 95% confidence interval [CI] 1.05-1.17). Similar associations were found by sex, follow-up time, and tumor subsite. In the MR analyses, a 1 standard deviation increment in IGF1 level, predicted based on genetic factors, was associated with a higher risk of colorectal cancer risk (odds ratio 1.08; 95% CI 1.03-1.12; P = 3.3 x 10-4). Level of IGFBP3, predicted based on genetic factors, was associated with colorectal cancer risk (odds ratio per 1 standard deviation increment, 1.12; 95% CI 1.06-1.18; P = 4.2 x 10-5). Colorectal cancer risk was associated with only 1 variant in the IGFBP3 gene region (rs11977526), which also associated with anthropometric traits and circulating level of IGF2. Conclusion(s): In an analysis of blood samples from almost 400,000 participants in the UK Biobank, we found an association between circulating level of IGF1 and colorectal cancer. Using genetic data from 52,865 cases with colorectal cancer and 46,287 controls, a higher level of IGF1, determined by genetic factors, was associated with colorectal cancer. Further studies are needed to determine how this signaling pathway might contribute to colorectal carcinogenesis.Copyright © 2020 AGA Institute | DOI: | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1053/j.gastro.2019.12.020 | PubMed URL: | 31884074 [http://www.ncbi.nlm.nih.gov/pubmed/?term=31884074] | ISSN: | 0016-5085 | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/29330 | Type: | Article | Subjects: | human adult anthropometry article blood sampling cancer incidence cancer patient cancer registry *cancer risk clinical trial cohort analysis *colon cancer/di [Diagnosis] *colon cancer/ep [Epidemiology] *colorectal cancer/di [Diagnosis] *colorectal cancer/ep [Epidemiology] confidence interval controlled study death certificate female follow up genetic variability genome-wide association study hazard ratio heredity high risk patient major clinical study male *Mendelian randomization analysis middle aged multivariate analysis odds ratio priority journal prospective study protein blood level *rectum cancer/di [Diagnosis] *rectum cancer/ep [Epidemiology] risk factor *serology serum United Kingdom acetylsalicylic acid ibuprofen *somatomedin binding protein 3/ec [Endogenous Compound] *somatomedin C/ec [Endogenous Compound] anthropometry blood sampling cancer cancer patient cancer registry cancer risk colon cancer colorectal cancer confidence interval certificate genetic variability genome-wide association study hazard ratio heredity high risk patient Mendelian randomization analysis multivariate analysis odds ratio protein blood level rectum cancer serology serum United Kingdom acetylsalicylic acid ibuprofen somatomedin binding protein 3 somatomedin C *colon cancer / *diagnosis / *epidemiology *colorectal cancer / *diagnosis / *epidemiology confidence interval controlled study death certificate female follow up genetic variability genome-wide association study hazard ratio heredity high risk patient human major clinical study male *Mendelian randomization analysis middle aged multivariate analysis odds ratio priority journal prospective study protein blood level anthropometry risk factor *serology serum United Kingdom adult *rectum cancer / *diagnosis / *epidemiology Article blood sampling cancer incidence cancer patient cancer registry *cancer risk clinical trial cohort analysis |
Type of Clinical Study or Trial: | Observational study (cohort, case-control, cross sectional or survey) |
Appears in Collections: | Articles |
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