Evidence map›Paper›PMID 35048991›Full record

ArticleJournal of the National Cancer Institute2022

Associations Between Glycemic Traits and Colorectal Cancer: A Mendelian Randomization Analysis.

Neil Murphy, Mingyang Song, Nikos Papadimitriou, Robert Carreras-Torres, Claudia Langenberg, Richard M Martin, Konstantinos K Tsilidis, Inês Barroso, Ji Chen, Timothy M Frayling and 15 more

Open access · bronzeAbstract read
In one paragraph

Article in Journal of the National Cancer Institute, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed, 3 pooled it
8.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

64 citing papers in PubMed, 3 syntheses or guidelines pooled it, 98 citations in OpenAlex.

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4 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

25 authors at 19 institutions in 10 countries.

Neil MurphyNutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France.ORCID 0000-0003-3347-8249
Mingyang SongDivision of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-1324-0316
Nikos PapadimitriouNutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France.
Robert Carreras-TorresColorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.ORCID 0000-0002-2925-734X
Claudia LangenbergMRC Epidemiology Unit, University of Cambridge, Cambridge, UK.ORCID 0000-0002-5017-7344
Richard M MartinMRC Integrative Epidemiology Unit (IEU), Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.ORCID 0000-0002-7992-7719
Konstantinos K TsilidisDepartment of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.ORCID 0000-0002-8452-8472
Inês BarrosoExeter Centre of Excellence in Diabetes (ExCEeD), Exeter Medical School, University of Exeter, Exeter, UK.ORCID 0000-0001-5800-4520
Ji ChenExeter Centre of Excellence in Diabetes (ExCEeD), Exeter Medical School, University of Exeter, Exeter, UK.
Timothy M FraylingExeter Centre of Excellence in Diabetes (ExCEeD), Exeter Medical School, University of Exeter, Exeter, UK.ORCID 0000-0001-8362-2603
Caroline J BullMRC Integrative Epidemiology Unit (IEU), Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.ORCID 0000-0002-2176-5120
Emma E VincentMRC Integrative Epidemiology Unit (IEU), Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.ORCID 0000-0002-8917-7384
Michelle CotterchioPrevention and Cancer Control, Clinical Institutes and Quality Programs, Ontario Health (Cancer Care Ontario), Ontario, Canada.
Stephen B GruberDepartment of Preventive Medicine, USC Norris Comprehensive Cancer Center, CA, USA.ORCID 0000-0001-8656-7822
Rish K PaiDepartment of Pathology and Laboratory Medicine, Mayo Clinic Arizona, Scottsdale, AZ, USA.ORCID 0000-0002-2692-221X
Polly A NewcombPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Aurora Perez-CornagoCancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.ORCID 0000-0002-5652-356X
Franzel J B van DuijnhovenDivision of Human Nutrition and Health, Wageningen University and Research, Wageningen, the Netherlands.ORCID 0000-0001-8367-2352
Bethany Van GuelpenDepartment of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.ORCID 0000-0002-9692-101X
Pavel VodickaDepartment of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic.
Alicja WolkInstitute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0001-7387-6845
Anna H WuUniversity of Southern California, Preventative Medicine, Los Angeles, CA, USA.
Ulrike PetersPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Andrew T ChanDivision of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-7284-6767
Marc J GunterNutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France.ORCID 0000-0001-5472-6761
Centre international de recherche sur le cancer · FRUniversity of Exeter · GBUniversity of Bristol · GBUniversity of Southern California · USBellvitge University Hospital · ESBrigham and Women's Hospital · USCancer Care Ontario · CACharles University · CZFred Hutch Cancer Center · USHarvard University · USKarolinska Institutet · SEMayo Clinic in Arizona · USUmeå University · SEUniversity Hospitals Bristol NHS Foundation Trust · GBUniversity of Cambridge · GBUniversity of Ioannina · GRUniversity of Oxford · GBUniversity of Washington · USWageningen University & Research · NL

Funding

Translational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Marian Esvelt · 1985 to 2026
$296.4M
Data sharing: the Colon Cancer Family Registry CohortU01CA167551 · NCI · UNIVERSITY OF MELBOURNE · PI Daniel David BUCHANAN, Steven Gallinger · 2018 to 2026
$16.8M
PCPT and SELECT Cohorts: Core Infrastructure Support for Cancer ResearchU01CA182883 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI TANGEN, CATHERINE M., THOMPSON, IAN M. · 2019 to 2023
$5.4M
Advancing equity in colorectal cancer genetic risk prediction through expansion of racial/ethnic minority representationR01CA244588 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI PETERS, ULRIKE · 2020 to 2024
$3.5M
Cancer Research UK 29019Cancer Research UK C18281/A29019Medical Research Council G1000143Medical Research Council MC_UU_00006/1NCI NIH HHS P30 CA015704NCI NIH HHS R01 CA244588NCI NIH HHS U01 CA182883World Health Organization 001
6 · The paper itself

Abstract

backgroundGlycemic 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.

methodsGenome-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).

resultsIn 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.

conclusionsOur 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.

Indexed as

Colorectal NeoplasmsDiabetes Mellitus, Type 2HyperinsulinismBlood GlucoseFemaleGenome-Wide Association StudyGlycated HemoglobinHumansInsulinMaleMendelian Randomization AnalysisPolymorphism, Single NucleotideRisk FactorsBlood GlucoseGlycated HemoglobinInsulin

Identifiers

PMID35048991
PMCPMC9086764
OpenAlexW4205821233

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LicenceCC BY-NC
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.