Evidence map›Paper›PMID 37171501›Full record

ArticleDiabetologia2023

Genetically proxied glucose-lowering drug target perturbation and risk of cancer: a Mendelian randomisation analysis.

James Yarmolinsky, Emmanouil Bouras, Andrei Constantinescu, Kimberley Burrows, Caroline J Bull, Emma E Vincent, Richard M Martin, Olympia Dimopoulou, Sarah J Lewis, Victor Moreno and 16 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Diabetologia, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 3 pooled it
5.5field-weighted citation impact, top 4% 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

25 citing papers in PubMed, 3 syntheses or guidelines pooled it, 36 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Observational
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review
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

26 authors at 17 institutions in 8 countries.

James Yarmolinsky *MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK. james.yarmolinsky@bristol.ac.uk.
Emmanouil Bouras *Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece.
Andrei ConstantinescuMRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Kimberley BurrowsMRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Caroline J BullMRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Emma E VincentMRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Richard M MartinMRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Olympia DimopoulouMRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Sarah J LewisMRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Victor MorenoBiomarkers and Susceptibility Unit, Oncology Data Analytics Program, Catalan Institute of Oncology (ICO), L'Hospitalet de Llobregat, Barcelona, Spain.
Marijana VujkovicCorporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.
Kyong-Mi ChangCorporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.
Benjamin F VoightCorporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.
Philip S TsaoVA Palo Alto Epidemiology Research and Information Center for Genomics, VA Palo Alto Health Care System, Palo Alto, CA, USA.
Marc J GunterNutrition and Metabolism Section, International Agency for Research on Cancer, World Health Organization, Lyon, France.
Jochen HampeDepartment of Medicine I, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden, Germany.
Andrew J PellattUniversity of Texas MD Anderson Cancer Center, Houston, TX, USA.
Paul D P PharoahDepartment of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Robert E SchoenDepartment of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Steven GallingerLunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.
Mark A JenkinsCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia.
Rish K PaiDepartment of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Scottsdale, AZ, USA.
PRACTICAL consortium
VA Million Veteran Program
Dipender GillDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College London, St Mary's Campus, London, UK.
Kostas K TsilidisDepartment of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece.
University of Bristol · GBUniversity of Ioannina · GRImperial College London · GBPhiladelphia VA Medical Center · USAt Bristol · GBBellvitge University Hospital · ESCentre international de recherche sur le cancer · FRMayo Clinic in Arizona · USMount Sinai Hospital · CATechnische Universität Dresden · DEThe University of Melbourne · AUThe University of Texas MD Anderson Cancer Center · USTranslational Therapeutics (United States) · USUniversity Hospitals Bristol NHS Foundation Trust · GBUniversity of Cambridge · GBUniversity of Pittsburgh Medical Center · USVA Palo Alto Health Care System · US

Funding

Translational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · 1985 to 2025
$104.6M
Translational Research Central ServicesP30CA006973 · JOHNS HOPKINS UNIVERSITY · 1985 to 2025
$45.1M
MOLECULAR EPIDEMIOLOGY OF COLORECTAL CANCERR01CA081488 · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 1999 to 2005
$6.2M
CLUE STUDIES--EVALUATING BIOMARKERS OF CARCINOGENESISU01CA086308 · JOHNS HOPKINS UNIVERSITY · 2000 to 2004
$4.2M
GENETIC EPIDEMIOLOGIC STUDIES OF POLYPS AND CANCERR01CA059045 · FRED HUTCHINSON CANCER RESEARCH CENTER · 1994 to 2003
$2.8M
GENE-ENVIRONMENT INTERACTIONS: THE ODYSSEY COHORTU01AG018033 · JOHNS HOPKINS UNIVERSITY · 1999 to 2003
$2.8M
Transdisciplinary Team Science in Colorectal Cancer Prognosis: the ColoCare StudyU01CA206110 · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2025 to 2025
$1.9M
Colon Cancer Family Registry CohortU01CA167551 · UNIVERSITY OF MELBOURNE · 2025 to 2025
$1.8M
HORMONE REPLACEMENT THERAPY AND LARGE BOWEL CANCER RISKR01CA076366 · FRED HUTCHINSON CANCER RESEARCH CENTER · 1998 to 2002
$1.2M
Colon Cancer Pathways: Hyperplastic Polyps and AdenomasR01CA097325 · FRED HUTCHINSON CANCER RESEARCH CENTER · 2004 to 2005
$1.1M
A genomics-based strategy to precision phenotyping and drug repositioning in cardiometabolic diseasesR01DK134575 · UNIVERSITY OF PENNSYLVANIA · 2025 to 2025
$325k
NMR detection of tumor differentiationR01CA114347 · UNIVERSITY OF PENNSYLVANIA · 2005 to 2005
$273k
BLRD VA I01 BX003362Cancer Research UK 28534Cancer Research UK 29017Cancer Research UK 29019Medical Research Council MR/M012190/1NCATS NIH HHS KL2 TR000421NCCDPHP CDC HHS U58 DP002333NCI NIH HHS HHSN261201700006INCI NIH HHS K05 CA152715NCI NIH HHS K05 CA154337NCI NIH HHS P30 CA006973NCI NIH HHS P30 CA015704NCI NIH HHS R01 CA059045NCI NIH HHS R01 CA076366NCI NIH HHS R01 CA081488NCI NIH HHS R01 CA097325NCI NIH HHS R01 CA114347NCI NIH HHS R01 CA201407NCI NIH HHS R01 CA207371NCI NIH HHS R03 CA153323NCI NIH HHS R21 CA191312NCI NIH HHS U01 CA086308NCI NIH HHS U01 CA122839NCI NIH HHS U01 CA137088NCI NIH HHS U01 CA164930NCI NIH HHS U01 CA167551NCI NIH HHS U01 CA206110NCI NIH HHS U19 CA148107NCI NIH HHS U24 CA074794NHLBI NIH HHS HHSN268201100046CNHLBI NIH HHS HHSN268201200008INIA NIH HHS HHSN271201100004CNIA NIH HHS U01 AG018033NIDDK NIH HHS R01 DK134575NIDDK NIH HHS UM1 DK126194NIH HHS S10 OD028685WHI NIH HHS HHSN268201100001CWHI NIH HHS HHSN268201100002CWHI NIH HHS HHSN268201100003CWHI NIH HHS HHSN268201100004CWorld Health Organization 001
6 · The paper itself

Abstract

aims/hypothesisEpidemiological studies have generated conflicting findings on the relationship between glucose-lowering medication use and cancer risk. Naturally occurring variation in genes encoding glucose-lowering drug targets can be used to investigate the effect of their pharmacological perturbation on cancer risk.

methodsWe developed genetic instruments for three glucose-lowering drug targets (peroxisome proliferator activated receptor γ [PPARG]; sulfonylurea receptor 1 [ATP binding cassette subfamily C member 8 (ABCC8)]; glucagon-like peptide 1 receptor [GLP1R]) using summary genetic association data from a genome-wide association study of type 2 diabetes in 148,726 cases and 965,732 controls in the Million Veteran Program. Genetic instruments were constructed using cis-acting genome-wide significant (p<5×10

resultsIn MR analysis, genetically proxied PPARG perturbation was weakly associated with higher risk of prostate cancer (for PPARG perturbation equivalent to a 1 unit decrease in inverse rank normal transformed HbA CONCLUSIONS/

interpretationOur drug target MR analyses did not find consistent evidence to support an association of genetically proxied PPARG, ABCC8 or GLP1R perturbation with breast, colorectal, prostate or overall cancer risk. Further evaluation of these drug targets using alternative molecular epidemiological approaches may help to further corroborate the findings presented in this analysis. DATA AVAILABILITY: Summary genetic association data for select cancer endpoints were obtained from the public domain: breast cancer ( https://bcac.ccge.medschl.cam.ac.uk/bcacdata/ ); and overall prostate cancer ( http://practical.icr.ac.uk/blog/ ). Summary genetic association data for colorectal cancer can be accessed by contacting GECCO (kafdem at fredhutch.org). Summary genetic association data on advanced prostate cancer can be accessed by contacting PRACTICAL (practical at icr.ac.uk). Summary genetic association data on type 2 diabetes from Vujkovic et al (Nat Genet, 2020) can be accessed through dbGAP under accession number phs001672.v3.p1 (pha004945.1 refers to the European-specific summary statistics). UK Biobank data can be accessed by registering with UK Biobank and completing the registration form in the Access Management System (AMS) ( https://www.ukbiobank.ac.uk/enable-your-research/apply-for-access ).

Indexed as

Breast NeoplasmsColorectal NeoplasmsDiabetes Mellitus, Type 2Prostatic NeoplasmsGenome-Wide Association StudyGlucoseHumansMaleMendelian Randomization AnalysisPolymorphism, Single NucleotidePPAR gammaRisk FactorsGlucosePPAR gammaABCC8Breast cancerColorectal cancerGLP1RGlucose-lowering drug targetsMendelian randomisationPPARGProstate cancer

Identifiers

PMID37171501
PMCPMC10317892
OpenAlexW4376225588

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.