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Associations between Glycemic Traits and Colorectal Cancer : A Mendelian Randomization Analysis
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- Murphy, Neil (författare)
- Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France
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- Song, Mingyang (författare)
- Division 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
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- Papadimitriou, Nikos (författare)
- Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France
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- Carreras-Torres, Robert (författare)
- Colorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain
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- Langenberg, Claudia (författare)
- MRC 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
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- Martin, Richard M (författare)
- MRC 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
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- Tsilidis, Konstantinos K (författare)
- 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, United Kingdom
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- Barroso, Inês (författare)
- Exeter Centre of Excellence in Diabetes (ExCEeD), Exeter Medical School, University of Exeter, Exeter, United Kingdom
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- Chen, Ji (författare)
- Exeter Centre of Excellence in Diabetes (ExCEeD), Exeter Medical School, University of Exeter, Exeter, United Kingdom
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- Frayling, Timothy M (författare)
- Exeter 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
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- Bull, Caroline J (författare)
- MRC 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
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- Vincent, Emma E (författare)
- MRC 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
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- Cotterchio, Michelle (författare)
- Prevention and Cancer Control, Clinical Institutes and Quality Programs, Ontario Health (Cancer Care Ontario), ON, Canada
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- Gruber, Stephen B (författare)
- Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, CA, United States; Keck School of Medicine, University of Southern California, CA, Los Angeles, United States
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- Pai, Rish K (författare)
- Department of Pathology and Laboratory Medicine, Mayo Clinic Arizona, AZ, Scottsdale, United States
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- Newcomb, Polly A (författare)
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States
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- Perez-Cornago, Aurora (författare)
- Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
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- Van Duijnhoven, Franzel J. B (författare)
- Division of Human Nutrition and Health, Wageningen University and Research, Wageningen, Netherlands
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- van Guelpen, Bethany (författare)
- Umeå universitet,Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM),Patologi,Onkologi
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- Vodicka, Pavel (författare)
- Department 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
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- Wolk, Alicja (författare)
- Karolinska Institutet
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- Wu, Anna H. (författare)
- University of Southern California, Preventative Medicine, CA, Los Angeles, United States
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- Peters, Ulrike (författare)
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States; Department of Epidemiology, University of Washington, WA, Seattle, United States
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- Chan, Andrew T (författare)
- Division 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
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- Gunter, Marc J (författare)
- Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France
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Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France Division 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 TH. 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)
- 2022-01-20
- 2022
- Engelska.
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 114:5, s. 740-752
- Relaterad länk:
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https://doi.org/10.1...
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https://academic.oup...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- 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.
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 -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
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- Av författaren/redakt...
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Murphy, Neil
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Song, Mingyang
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Papadimitriou, N ...
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Carreras-Torres, ...
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Langenberg, Clau ...
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Martin, Richard ...
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Tsilidis, Konsta ...
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Barroso, Inês
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Chen, Ji
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Frayling, Timoth ...
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Bull, Caroline J
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Vincent, Emma E
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Cotterchio, Mich ...
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Gruber, Stephen ...
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Pai, Rish K
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Newcomb, Polly A
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Perez-Cornago, A ...
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Van Duijnhoven, ...
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van Guelpen, Bet ...
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Vodicka, Pavel
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Wolk, Alicja
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Wu, Anna H.
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Peters, Ulrike
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Chan, Andrew T
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Gunter, Marc J
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Umeå universitet
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Karolinska Institutet