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  • Murphy, NeilNutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France (författare)

Associations between Glycemic Traits and Colorectal Cancer : A Mendelian Randomization Analysis

  • Artikel/kapitelEngelska2022

Förlag, utgivningsår, omfång ...

  • 2022-01-20
  • Oxford University Press (OUP),2022
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:umu-203141
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-203141URI
  • https://doi.org/10.1093/jnci/djac011DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:148938609URI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

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Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • Background: Glycemic traits - such as hyperinsulinemia, hyperglycemia, and type 2 diabetes - have been associated with higher colorectal cancer risk in observational studies; however, causality of these associations is uncertain. We used Mendelian randomization (MR) to estimate the causal effects of fasting insulin, 2-hour glucose, fasting glucose, glycated hemoglobin (HbA1c), and type 2 diabetes with colorectal cancer. Methods: Genome-wide association study summary data were used to identify genetic variants associated with circulating levels of fasting insulin (n = 34), 2-hour glucose (n = 13), fasting glucose (n = 70), HbA1c (n = 221), and type 2 diabetes (n = 268). Using 2-sample MR, we examined these variants in relation to colorectal cancer risk (48 214 case patient and 64 159 control patients). Results: In inverse-variance models, higher fasting insulin levels increased colorectal cancer risk (odds ratio [OR] per 1-SD = 1.65, 95% confidence interval [CI] = 1.15 to 2.36). We found no evidence of any effect of 2-hour glucose (OR per 1-SD = 1.02, 95% CI = 0.86 to 1.21) or fasting glucose (OR per 1-SD = 1.04, 95% CI = 0.88 to 1.23) concentrations on colorectal cancer risk. Genetic liability to type 2 diabetes (OR per 1-unit increase in log odds = 1.04, 95% CI = 1.01 to 1.07) and higher HbA1c levels (OR per 1-SD = 1.09, 95% CI = 1.00 to 1.19) increased colorectal cancer risk, although these findings may have been biased by pleiotropy. Higher HbA1c concentrations increased rectal cancer risk in men (OR per 1-SD = 1.21, 95% CI = 1.05 to 1.40), but not in women. Conclusions: Our results support a causal effect of higher fasting insulin, but not glucose traits or type 2 diabetes, on increased colorectal cancer risk. This suggests that pharmacological or lifestyle interventions that lower circulating insulin levels may be beneficial in preventing colorectal tumorigenesis.

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Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Song, MingyangDivision of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, MA, Boston, United States; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, MA, Boston, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, MA, Boston, United States; Department of Nutrition, Harvard T.H. Chan School of Public Health, MA, Boston, United States (författare)
  • Papadimitriou, NikosNutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France (författare)
  • Carreras-Torres, RobertColorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain (författare)
  • Langenberg, ClaudiaMRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom; Computational Medicine, Berlin Institute of Health, Charite University Medicine, Berlin, Germany; Health Data Research UK, Wellcome Genome Campus, University of Cambridge, Cambridge, United Kingdom (författare)
  • Martin, Richard MMRC Integrative Epidemiology Unit (IEU), Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom; Bristol Medical School, Department of Population Health Sciences, University of Bristol, Bristol, United Kingdom; National Institute for Health Research (NIHR), Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust, University of Bristol, Bristol, United Kingdom (författare)
  • Tsilidis, Konstantinos KDepartment 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, United Kingdom (författare)
  • Barroso, InêsExeter Centre of Excellence in Diabetes (ExCEeD), Exeter Medical School, University of Exeter, Exeter, United Kingdom (författare)
  • Chen, JiExeter Centre of Excellence in Diabetes (ExCEeD), Exeter Medical School, University of Exeter, Exeter, United Kingdom (författare)
  • Frayling, Timothy MExeter Centre of Excellence in Diabetes (ExCEeD), Exeter Medical School, University of Exeter, Exeter, United Kingdom; Department of Human Genetics, University of Exeter, Research Innovation Learning & Development (RILD) Building, Royal Devon and Exeter Hospital, Exeter, United Kingdom (författare)
  • Bull, Caroline JMRC Integrative Epidemiology Unit (IEU), Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom; Bristol Medical School, Department of Population Health Sciences, University of Bristol, Bristol, United Kingdom; School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom (författare)
  • Vincent, Emma EMRC Integrative Epidemiology Unit (IEU), Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom; Bristol Medical School, Department of Population Health Sciences, University of Bristol, Bristol, United Kingdom; School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom (författare)
  • Cotterchio, MichellePrevention and Cancer Control, Clinical Institutes and Quality Programs, Ontario Health (Cancer Care Ontario), ON, Canada (författare)
  • Gruber, Stephen BDepartment of Preventive Medicine, USC Norris Comprehensive Cancer Center, CA, United States; Keck School of Medicine, University of Southern California, CA, Los Angeles, United States (författare)
  • Pai, Rish KDepartment of Pathology and Laboratory Medicine, Mayo Clinic Arizona, AZ, Scottsdale, United States (författare)
  • Newcomb, Polly APublic Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States (författare)
  • Perez-Cornago, AuroraCancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom (författare)
  • Van Duijnhoven, Franzel J. BDivision of Human Nutrition and Health, Wageningen University and Research, Wageningen, Netherlands (författare)
  • van Guelpen, BethanyUmeå universitet,Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM),Patologi,Onkologi(Swepub:umu)beyvan99 (författare)
  • Vodicka, PavelDepartment of Molecular Biology of Cancer, Institute of Experimental Medicine, Czech Academy of Sciences, Prague, Czech Republic; Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic; Faculty of Medicine and Biomedical Center in Pilsen, Charles University, Pilsen, Czech Republic (författare)
  • Wolk, AlicjaKarolinska Institutet (författare)
  • Wu, Anna H.University of Southern California, Preventative Medicine, CA, Los Angeles, United States (författare)
  • Peters, UlrikePublic Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; Department of Epidemiology, University of Washington, WA, Seattle, United States (författare)
  • Chan, Andrew TDivision of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, MA, Boston, United States; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, MA, Boston, United States; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, MA, Boston, United States (författare)
  • Gunter, Marc JNutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France (författare)
  • Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, FranceDivision of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, MA, Boston, United States; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, MA, Boston, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, MA, Boston, United States; Department of Nutrition, Harvard T.H. Chan School of Public Health, MA, Boston, United States (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Journal of the National Cancer Institute: Oxford University Press (OUP)114:5, s. 740-7520027-88741460-2105

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