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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

N. Murphy, R. Carreras-Torres, M. Song, AT. Chan, RM. Martin, N. Papadimitriou, N. Dimou, KK. Tsilidis, B. Banbury, KE. Bradbury, J. Besevic, S. Rinaldi, E. Riboli, AJ. Cross, RC. Travis, C. Agnoli, D. Albanes, SI. Berndt, S. Bézieau, DT. Bishop,...

. 2020 ; 158 (5) : 1300-1312.e20. [pub] 20191227

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc20025103

Grantová podpora
HHSN268201100001C WHI NIH HHS - United States
R01 CA059045 NCI NIH HHS - United States
U01 CA074799 NCI NIH HHS - United States
K05 CA154337 NCI NIH HHS - United States
R01 CA201407 NCI NIH HHS - United States
KL2 TR002317 NCATS NIH HHS - United States
KL2 TR000421 NCATS NIH HHS - United States
U24 CA074800 NCI NIH HHS - United States
P30 CA006973 NCI NIH HHS - United States
P30 CA076292 NCI NIH HHS - United States
C8221/A19170 Cancer Research UK - United Kingdom
R01 CA137178 NCI NIH HHS - United States
U24 CA074783 NCI NIH HHS - United States
U24 CA074806 NCI NIH HHS - United States
K07 CA190673 NCI NIH HHS - United States
U24 CA074794 NCI NIH HHS - United States
P30 DK034987 NIDDK NIH HHS - United States
14136 Cancer Research UK - United Kingdom
U01 CA137088 NCI NIH HHS - United States
R01 CA076366 NCI NIH HHS - United States
MC_QA137853 Medical Research Council - United Kingdom
U01 CA097735 NCI NIH HHS - United States
U19 CA148107 NCI NIH HHS - United States
T32 ES013678 NIEHS NIH HHS - United States
HHSN271201100004C NIA NIH HHS - United States
Department of Health - United Kingdom
R01 CA207371 NCI NIH HHS - United States
R01 CA151993 NCI NIH HHS - United States
P30 CA014089 NCI NIH HHS - United States
R01 CA189184 NCI NIH HHS - United States
P50 CA127003 NCI NIH HHS - United States
C490/A16561 Cancer Research UK - United Kingdom
1000143 Medical Research Council - United Kingdom
CRT 43821 CIHR - Canada
P30 CA008748 NCI NIH HHS - United States
HHSN261201500005C NCI NIH HHS - United States
R35 CA197735 NCI NIH HHS - United States
HHSN268201100004C WHI NIH HHS - United States
C570/A16491 Cancer Research UK - United Kingdom
UM1 CA182883 NCI NIH HHS - United States
U01 CA122839 NCI NIH HHS - United States
UM1 CA167552 NCI NIH HHS - United States
MR/M012190/1 Medical Research Council - United Kingdom
U01 CA167551 NCI NIH HHS - United States
C588/A19167 Cancer Research UK - United Kingdom
U01 CA074800 NCI NIH HHS - United States
HHSN268201100046C NHLBI NIH HHS - United States
HHSN268201100003C WHI NIH HHS - United States
P01 CA087969 NCI NIH HHS - United States
R01 CA042182 NCI NIH HHS - United States
U01 CA074794 NCI NIH HHS - United States
U01 CA167552 NCI NIH HHS - United States
U01 CA074806 NCI NIH HHS - United States
MC_PC_12028 Medical Research Council - United Kingdom
P01 CA196569 NCI NIH HHS - United States
MC_PC_17228 Medical Research Council - United Kingdom
R01 CA136726 NCI NIH HHS - United States
UM1 CA186107 NCI NIH HHS - United States
U01 CA206110 NCI NIH HHS - United States
HHSN268201100002C WHI NIH HHS - United States
P01 CA055075 NCI NIH HHS - United States
U24 CA097735 NCI NIH HHS - United States
U24 CA074799 NCI NIH HHS - United States
R03 CA153323 NCI NIH HHS - United States
R01 CA097325 NCI NIH HHS - United States
HHSN268201200008I NHLBI NIH HHS - United States
K05 CA152715 NCI NIH HHS - United States
R01 CA197350 NCI NIH HHS - United States
MR/L01629X/1 Medical Research Council - United Kingdom
R01 CA063464 NCI NIH HHS - United States
P01 CA033619 NCI NIH HHS - United States
U01 CA074783 NCI NIH HHS - United States
P30 CA015704 NCI NIH HHS - United States
NV17-30920A MZ0 CEP - Centrální evidence projektů

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. METHODS: 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 × 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 × 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. CONCLUSIONS: 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.

Behavioral and Epidemiology Research Group American Cancer Society Atlanta Georgia

Biomedicine Institute University of León León Spain

Bristol Medical School Department of Population Health Sciences University of Bristol Bristol UK

Broad Institute of MIT and Harvard Cambridge Massachusetts

Cancer Epidemiology Division Cancer Council Victoria Melbourne Victoria Australia

Cancer Epidemiology Unit Nuffield Department of Population Health University of Oxford Oxford UK

Cancer Immunology and Cancer Epidemiology Programs Dana Farber Harvard Cancer Center Boston Massachusetts

Center for Gastrointestinal Biology and Disease University of North Carolina Chapel Hill North Carolina

Center for Public Health Genomics University of Virginia Charlottesville Virginia

Centre for Epidemiology and Biostatistics Melbourne School of Population and Global Health The University of Melbourne Melbourne Victoria Australia

Centre for Public Health Research Massey University Wellington New Zealand

CESP Fac de médecine Université Paris Saclay Fac de médecine UVSQ 94805 Villejuif France

Channing Division of Network Medicine Brigham and Women's Hospital and Harvard Medical School Boston Massachusetts

CIBER in Epidemiology and Public Health Madrid Spain

Clinical and Translational Epidemiology Unit Massachusetts General Hospital and Harvard Medical School Boston Massachusetts

Clinical Genetics Service Department of Medicine Memorial Sloan Kettering Cancer Center New York New York

Colorectal Cancer Group ONCOBELL Program Bellvitge Biomedical Research Institute L'Hospitalet de Llobregat Barcelona Spain

Colorectal Oncogenomics Group Department of Clinical Pathology The University of Melbourne Parkville Victoria 3010 Australia

Department of Biostatistics University of Washington Seattle Washington

Department of Cancer Biology and Genetics and the Comprehensive Cancer Center The Ohio State University Columbus Ohio

Department of Clinical Genetics Karolinska University Hospital Stockholm Sweden

Department of Clinical Sciences Faculty of Medicine University of Barcelona Barcelona Spain

Department of Community Medicine and Epidemiology Lady Davis Carmel Medical Center Haifa Israel

Department of Epidemiology and Biostatistics School of Public Health Imperial College London London UK

Department of Epidemiology Harvard T H Chan School of Public Health Harvard University Boston Massachusetts

Department of Epidemiology Johns Hopkins Bloomberg School of Public Health Baltimore Maryland

Department of Epidemiology Regional Health Council IMIB Arrixaca Murcia University Murcia Spain

Department of Epidemiology University of Washington Seattle Washington

Department of Family Medicine University of Virginia Charlottesville Virginia

Department of General and Thoracic Surgery University Hospital Schleswig Holstein Campus Kiel Kiel Germany

Department of Hygiene and Epidemiology University of Ioannina School of Medicine Ioannina Greece

Department of Internal Medicine University of Utah Salt Lake City Utah

Department of Medicine 1 University Hospital Dresden Technische Universität Dresden Dresden Germany

Department of Medicine and Epidemiology University of Pittsburgh Medical Center Pittsburgh Pennsylvania

Department of Medicine Samuel Oschin Comprehensive Cancer Institute Cedars Sinai Medical Center Los Angeles California

Department of Medicine Weill Cornell Medical College New York New York

Department of Molecular Biology of Cancer Institute of Experimental Medicine of the Czech Academy of Sciences Prague Czech Republic

Department of Molecular Medicine and Surgery Karolinska Institute Stockholm Sweden

Department of Nutrition Harvard T H Chan School of Public Health Boston Massachusetts

Department of Preventive Medicine and USC Norris Comprehensive Cancer Center Keck School of Medicine University of Southern California Los Angeles California

Department of Preventive Medicine Chonnam National University Medical School Gwangju Korea

Department of Radiation Sciences Oncology Unit Umeå University Umeå Sweden

Division of Cancer Epidemiology and Genetics National Cancer Institute National Institutes of Health Bethesda Maryland

Division of Cancer Epidemiology German Cancer Research Center Heidelberg Germany

Division of Clinical Epidemiology and Aging Research German Cancer Research Center Heidelberg Germany

Division of Epidemiology Department of Medicine Vanderbilt Ingram Cancer Center Vanderbilt Epidemiology Center Vanderbilt University School of Medicine Nashville Tennessee

Division of Gastroenterology Massachusetts General Hospital and Harvard Medical School Boston Massachusetts

Division of Human Genetics Department of Internal Medicine The Ohio State University Comprehensive Cancer Center Columbus Ohio

Division of Human Nutrition and Health Wageningen University and Research Wageningen the Netherlands

Division of Preventive Oncology German Cancer Research Center Heidelberg Germany

Division of Research Kaiser Permanente Northern California Oakland California

Epidemiology and Prevention Unit Fondazione IRCCS Istituto Nazionale dei Tumori Milan Italy

Faculty of Medicine and Biomedical Center in Pilsen Charles University Pilsen Czech Republic

Gastroenterology Department Institut d'Investigacions Biomèdiques August Pi i Sunyer University of Barcelona Barcelona Spain

Genetic Medicine and Family Cancer Clinic The Royal Melbourne Hospital Parkville Victoria Australia

German Cancer Consortium Heidelberg Germany

Gustave Roussy F 94805 Villejuif France

Huntsman Cancer Institute and Department of Population Health Sciences University of Utah Salt Lake City Utah

Institute for Health Research Kaiser Permanente Colorado Denver Colorado

Institute of Biology and Medical Genetics 1st Faculty of Medicine Charles University Prague Czech Republic

Institute of Cancer Research Department of Medicine 1 Medical University Vienna Vienna Austria

Institute of Environmental Medicine Karolinska Institute Stockholm Sweden

Institute of Medical Research at St James's University of Leeds Leeds UK

Jeonnam Regional Cancer Center Chonnam National University Hwasun Hospital Hwasun Korea

Julius Center for Health Sciences and Primary Care University Medical Center Utrecht Utrecht The Netherlands

Laboratoire de Mathématiques Appliquées MAP5 Université Paris Descartes France

Lunenfeld Tanenbaum Research Institute Mount Sinai Hospital University of Toronto Toronto Ontario Canada

Memorial University of Newfoundland Discipline of Genetics St John's Canada

MRC Integrative Epidemiology Unit Population Health Sciences Bristol Medical School University of Bristol Bristol UK

National Institute for Health Innovation School of Population Health The University of Auckland Auckland New Zealand

National Institute for Health Research Bristol Biomedical Research Centre University Hospitals Bristol NHS Foundation Trust and the University of Bristol Bristol UK

Precision Medicine School of Clinical Sciences at Monash Health Monash University Clayton Victoria Australia

Program in MPE Molecular Pathological Epidemiology Department of Pathology Brigham and Women's Hospital Harvard Medical School Boston Massachusetts

Public Health Sciences Division Fred Hutchinson Cancer Research Center Seattle Washington

Ruth and Bruce Rappaport Faculty of Medicine Technion Israel Institute of Technology Haifa Israel

School of Public Health University of Washington Seattle Washington

Section of Nutrition and Metabolism International Agency for Research on Cancer Lyon France

Service de Génétique Médicale Centre Hospitalier Universitaire Nantes Nantes France

SWOG Statistical Center Fred Hutchinson Cancer Research Center Seattle Washington

University of Hawaii Cancer Center Honolulu Hawaii

University of Melbourne Centre for Cancer Research Victorian Comprehensive Cancer Centre Parkville Victoria 3010 Australia

University of Southern California Preventive Medicine Los Angeles California

Wallenberg Centre for Molecular Medicine Umeå University Umeå Sweden

Citace poskytuje Crossref.org

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$a 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. METHODS: 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 × 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 × 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. CONCLUSIONS: 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.
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$a Song, Mingyang $u Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
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$a Martin, Richard M $u MRC Integrative Epidemiology Unit (IEU), Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK; Bristol Medical School, Department of Population Health Sciences, University of Bristol, Bristol, UK; National Institute for Health Research (NIHR) Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and the University of Bristol, Bristol, UK.
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$a Tsilidis, Konstantinos K $u Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
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$a Brenner, Hermann $u Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany; Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
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$a Buchanan, Daniel D $u Colorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, Parkville, Victoria 3010, Australia; University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, Victoria 3010, Australia; Genetic Medicine and Family Cancer Clinic, The Royal Melbourne Hospital, Parkville, Victoria, Australia.
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700    1_
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700    1_
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700    1_
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700    1_
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$a Li, Christopher I $u Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
700    1_
$a Li, Li $u Department of Family Medicine, University of Virginia, Charlottesville, Virginia.
700    1_
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700    1_
$a Martín, Vicente $u CIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain; Biomedicine Institute (IBIOMED), University of León, León, Spain.
700    1_
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700    1_
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700    1_
$a Newcomb, Polly A $u Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; School of Public Health, University of Washington, Seattle, Washington.
700    1_
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