Identification of potential mediators of the relationship between body mass index and colorectal cancer: a Mendelian randomization analysis

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Identification of potential mediators of the relationship between body mass index and colorectal cancer : a Mendelian randomization analysis

Bouras, Emmanouil (författare): Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece

Gill, Dipender (författare): Chief Scientific Advisor Office, Research and Early Development, Novo Nordisk, Copenhagen, Denmark; Department of Epidemiology and Biostatistics, Imperial College London, School of Public Health, London, United Kingdom

Zuber, Verena (författare): Department of Epidemiology and Biostatistics, Imperial College London, School of Public Health, London, United Kingdom

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Murphy, Neil (författare): Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France

Dimou, Niki (författare): Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France

Aleksandrova, Krasimira (författare): Faculty of Human and Health Sciences, University of Bremen, Bremen, Germany; Department Epidemiological Methods and Etiological Research, Leibniz Institute for Prevention Research and Epidemiology, Bremen, Germany

Lewis, Sarah J. (författare): Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom

Martin, Richard M. (författare): Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom; NIHR Bristol Biomedical Research Centre, University Hospitals Bristol, Weston NHS Foundation Trust, the University of Bristol, United Kingdom

Yarmolinsky, James (författare): Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom

Albanes, Demetrius (författare): Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States

Brenner, Hermann (författare): Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany; Division of Preventive Oncology, German Cancer Research Center (DKFZ), National Center for Tumor Diseases (NCT), Heidelberg, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany

Castellví-Bel, Sergi (författare): Department of Gastroenterology, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Hospital Clínic, Barcelona, Spain

Chan, Andrew T. (författare): Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, MA, Boston, United States; Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, MA, Boston, United States; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, MA, Boston, United States; Broad Institute of Harvard and MIT, MA, Cambridge, United States; Department of Epidemiology, Harvard TH Chan School of Public Health, Harvard University, MA, Boston, United States; Department of Immunology and Infectious Diseases, Harvard TH Chan School of Public Health, Harvard University, MA, Boston, United States

Cheng, Iona (författare): Department of Epidemiology and Biostatistics, University of California-San Francisco, CA, San Francisco, United States

Gruber, Stephen (författare): Department of Medical Oncology & Therapeutics Research, Center for Precision Medicine, City of Hope National Medical Center, CA, Duarte, United States

van Guelpen, Bethany (författare): Umeå universitet,Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM),Onkologi

Li, Christopher I. (författare): Public Health Sciences Division, Fred Hutchinson Cancer Center, WA, Seattle, United States

Le Marchand, Loic (författare): University of Hawaii Cancer Center, HI, Honolulu, United States

Newcomb, Polly A. (författare): Public Health Sciences Division, Fred Hutchinson Cancer Center, WA, Seattle, United States; Department of Epidemiology, University of Washington, WA, Seattle, United States

Ogino, Shuji (författare): Broad Institute of Harvard and MIT, MA, Cambridge, United States; Department of Epidemiology, Harvard TH Chan School of Public Health, Harvard University, MA, Boston, United States; Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, MA, Boston, United States; Department of Oncologic Pathology, Dana-Farber Cancer Institute, MA, Boston, United States

Pellatt, Andrew (författare): Department of Medicine, University of Utah, UT, Salt Lake City, United States

Schmit, Stephanie L. (författare): Genomic Medicine Institute, Cleveland Clinic, OH, Cleveland, United States; Population and Cancer Prevention Program, Case Comprehensive Cancer Center, OH, Cleveland, United States

Wolk, Alicja (författare): Karolinska Institutet,Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden

Wu, Anna H. (författare): University of Southern California, Preventative Medicine, CA, Los Angeles, United States

Peters, Ulrike (författare): Public Health Sciences Division, Fred Hutchinson Cancer Center, WA, Seattle, United States; Department of Epidemiology, University of Washington, WA, Seattle, United States

Gunter, Marc J. (författare): Department of Epidemiology and Biostatistics, Imperial College London, School of Public Health, London, United Kingdom; Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France

Tsilidis, Konstantinos K. (författare): Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece; Department of Epidemiology and Biostatistics, Imperial College London, School of Public Health, London, United Kingdom

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Oxford University Press, 2024
2024
Engelska.
Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 53:3

Relaterad länk:: https://doi.org/10.1...; visa fler...; https://umu.diva-por... (primary) (Raw object); https://urn.kb.se/re...; https://doi.org/10.1...; http://kipublication...; visa färre...

Tidskriftsartikel (refereegranskat)

Abstract Ämnesord

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Background: Colorectal cancer (CRC) is the third-most-common cancer worldwide and its rates are increasing. Elevated body mass index (BMI) is an established risk factor for CRC, although the molecular mechanisms behind this association remain unclear. Using the Mendelian randomization (MR) framework, we aimed to investigate the mediating effects of putative biomarkers and other CRC risk factors in the association between BMI and CRC.Methods: We selected as mediators biomarkers of established cancer-related mechanisms and other CRC risk factors for which a plausible association with obesity exists, such as inflammatory biomarkers, glucose homeostasis traits, lipids, adipokines, insulin-like growth factor 1 (IGF1), sex hormones, 25-hydroxy-vitamin D, smoking, physical activity (PA) and alcohol consumption. We used inverse-variance weighted MR in the main univariable analyses and performed sensitivity analyses (weighted-median, MR–Egger, Contamination Mixture). We used multivariable MR for the mediation analyses.Results: Genetically predicted BMI was positively associated with CRC risk [odds ratio per SD (5 kg/m2) ¼ 1.17, 95% CI: 1.08–1.24, P-value ¼ 1.4 × 10−5] and robustly associated with nearly all potential mediators. Genetically predicted IGF1, fasting insulin, low-density lipoprotein cholesterol, smoking, PA and alcohol were associated with CRC risk. Evidence for attenuation was found for IGF1 [explained 7% (95% CI: 2–13%) of the association], smoking (31%, 4–57%) and PA (7%, 2–11%). There was little evidence for pleiotropy, although smoking was bidirectionally associated with BMI and instruments were weak for PA.Conclusions: The effect of BMI on CRC risk is possibly partly mediated through plasma IGF1, whereas the attenuation of the BMI–CRC association by smoking and PA may reflect confounding and shared underlying mechanisms rather than mediation.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Hälsovetenskap -- Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Health Sciences -- Public Health, Global Health, Social Medicine and Epidemiology (hsv//eng)

Nyckelord

BMI
Body mass index
colorectal cancer
CRC
mediation analysis
Mendelian randomization
obesity

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Cancer och onkol ...

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Hälsovetenskap; och Folkhälsovetensk ...

Artiklar i publikationen: International Jo ...

Av lärosätet: Umeå universitet; Karolinska Institutet

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