Evidence map›Paper›PMID 26134033›Full record

ArticleJournal of the National Cancer Institute2015

Evidence of a Causal Association Between Insulinemia and Endometrial Cancer: A Mendelian Randomization Analysis.

Kevin T Nead, Stephen J Sharp, Deborah J Thompson, Jodie N Painter, David B Savage, Robert K Semple, Adam Barker, Australian National Endometrial Cancer Study Group (ANECS), John R B Perry, John Attia and 12 more

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

Article in Journal of the National Cancer Institute, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers, 10 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
93citing papers in PubMed, 10 pooled it
9.3field-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

93 citing papers in PubMed, 10 syntheses or guidelines pooled it, 185 citations in OpenAlex.

  1. Pooled it
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  7. Type 2 Diabetes and Cancer: An Umbrella Review of Observational and Mendelian Randomization Studies.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2021
    Pooled it
  8. Intentional weight loss, weight cycling, and endometrial cancer risk: a systematic review and meta-analysis.International journal of gynecological cancer : official journal of the International Gynecological Cancer Society · 2019
    Pooled it
  9. Pooled it
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  11. Article
  12. Article
  13. Diabetes, Obesity, and Endometrial Cancer: A Review.Current oncology (Toronto, Ont.) · 2025
    Review
  14. Observational
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  17. The Effect of Circulating Proteins and Their Role in Mediating Adiposity's Effect on Endometrial Cancer Risk: Mendelian Randomization and Colocalization Analyses.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2025
    Article
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33 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors at 10 institutions in 3 countries.

Kevin T NeadMRC Epidemiology Unit, University of Cambridge, Cambridge, UK (KTN, SJS, AB, JRBP, LAL, CL, NJW, RAS); Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (KTN); Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK (DJT, DFE, PDPP); Queensland Institute of Medical Research, Brisbane, Australia (JNP, ANECS, TO, ABS); University of Cambridge Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, Cambridge, UK (DBS, RKS); Hunter Medical Research Institute, John Hunter Hospital, Newcastle, Australia (JA, EH, RJS); Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, The University of Newcastle, Newcastle, Australia (JA, MM); Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK (AMD, DFE, PDPP); Centre for Information Based Medicine, School of Medicine and Public Health, University of Newcastle, Australia (EH, RJS).
Stephen J SharpMRC Epidemiology Unit, University of Cambridge, Cambridge, UK (KTN, SJS, AB, JRBP, LAL, CL, NJW, RAS); Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (KTN); Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK (DJT, DFE, PDPP); Queensland Institute of Medical Research, Brisbane, Australia (JNP, ANECS, TO, ABS); University of Cambridge Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, Cambridge, UK (DBS, RKS); Hunter Medical Research Institute, John Hunter Hospital, Newcastle, Australia (JA, EH, RJS); Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, The University of Newcastle, Newcastle, Australia (JA, MM); Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK (AMD, DFE, PDPP); Centre for Information Based Medicine, School of Medicine and Public Health, University of Newcastle, Australia (EH, RJS).
Deborah J ThompsonMRC Epidemiology Unit, University of Cambridge, Cambridge, UK (KTN, SJS, AB, JRBP, LAL, CL, NJW, RAS); Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (KTN); Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK (DJT, DFE, PDPP); Queensland Institute of Medical Research, Brisbane, Australia (JNP, ANECS, TO, ABS); University of Cambridge Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, Cambridge, UK (DBS, RKS); Hunter Medical Research Institute, John Hunter Hospital, Newcastle, Australia (JA, EH, RJS); Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, The University of Newcastle, Newcastle, Australia (JA, MM); Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK (AMD, DFE, PDPP); Centre for Information Based Medicine, School of Medicine and Public Health, University of Newcastle, Australia (EH, RJS).
Jodie N PainterMRC Epidemiology Unit, University of Cambridge, Cambridge, UK (KTN, SJS, AB, JRBP, LAL, CL, NJW, RAS); Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (KTN); Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK (DJT, DFE, PDPP); Queensland Institute of Medical Research, Brisbane, Australia (JNP, ANECS, TO, ABS); University of Cambridge Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, Cambridge, UK (DBS, RKS); Hunter Medical Research Institute, John Hunter Hospital, Newcastle, Australia (JA, EH, RJS); Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, The University of Newcastle, Newcastle, Australia (JA, MM); Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK (AMD, DFE, PDPP); Centre for Information Based Medicine, School of Medicine and Public Health, University of Newcastle, Australia (EH, RJS).
David B SavageMRC Epidemiology Unit, University of Cambridge, Cambridge, UK (KTN, SJS, AB, JRBP, LAL, CL, NJW, RAS); Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (KTN); Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK (DJT, DFE, PDPP); Queensland Institute of Medical Research, Brisbane, Australia (JNP, ANECS, TO, ABS); University of Cambridge Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, Cambridge, UK (DBS, RKS); Hunter Medical Research Institute, John Hunter Hospital, Newcastle, Australia (JA, EH, RJS); Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, The University of Newcastle, Newcastle, Australia (JA, MM); Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK (AMD, DFE, PDPP); Centre for Information Based Medicine, School of Medicine and Public Health, University of Newcastle, Australia (EH, RJS).
Robert K SempleMRC Epidemiology Unit, University of Cambridge, Cambridge, UK (KTN, SJS, AB, JRBP, LAL, CL, NJW, RAS); Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (KTN); Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK (DJT, DFE, PDPP); Queensland Institute of Medical Research, Brisbane, Australia (JNP, ANECS, TO, ABS); University of Cambridge Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, Cambridge, UK (DBS, RKS); Hunter Medical Research Institute, John Hunter Hospital, Newcastle, Australia (JA, EH, RJS); Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, The University of Newcastle, Newcastle, Australia (JA, MM); Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK (AMD, DFE, PDPP); Centre for Information Based Medicine, School of Medicine and Public Health, University of Newcastle, Australia (EH, RJS).
Adam BarkerMRC Epidemiology Unit, University of Cambridge, Cambridge, UK (KTN, SJS, AB, JRBP, LAL, CL, NJW, RAS); Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (KTN); Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK (DJT, DFE, PDPP); Queensland Institute of Medical Research, Brisbane, Australia (JNP, ANECS, TO, ABS); University of Cambridge Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, Cambridge, UK (DBS, RKS); Hunter Medical Research Institute, John Hunter Hospital, Newcastle, Australia (JA, EH, RJS); Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, The University of Newcastle, Newcastle, Australia (JA, MM); Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK (AMD, DFE, PDPP); Centre for Information Based Medicine, School of Medicine and Public Health, University of Newcastle, Australia (EH, RJS).
Australian National Endometrial Cancer Study Group (ANECS)
John R B PerryMRC Epidemiology Unit, University of Cambridge, Cambridge, UK (KTN, SJS, AB, JRBP, LAL, CL, NJW, RAS); Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (KTN); Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK (DJT, DFE, PDPP); Queensland Institute of Medical Research, Brisbane, Australia (JNP, ANECS, TO, ABS); University of Cambridge Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, Cambridge, UK (DBS, RKS); Hunter Medical Research Institute, John Hunter Hospital, Newcastle, Australia (JA, EH, RJS); Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, The University of Newcastle, Newcastle, Australia (JA, MM); Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK (AMD, DFE, PDPP); Centre for Information Based Medicine, School of Medicine and Public Health, University of Newcastle, Australia (EH, RJS).
John AttiaMRC Epidemiology Unit, University of Cambridge, Cambridge, UK (KTN, SJS, AB, JRBP, LAL, CL, NJW, RAS); Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (KTN); Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK (DJT, DFE, PDPP); Queensland Institute of Medical Research, Brisbane, Australia (JNP, ANECS, TO, ABS); University of Cambridge Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, Cambridge, UK (DBS, RKS); Hunter Medical Research Institute, John Hunter Hospital, Newcastle, Australia (JA, EH, RJS); Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, The University of Newcastle, Newcastle, Australia (JA, MM); Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK (AMD, DFE, PDPP); Centre for Information Based Medicine, School of Medicine and Public Health, University of Newcastle, Australia (EH, RJS).
Alison M DunningMRC Epidemiology Unit, University of Cambridge, Cambridge, UK (KTN, SJS, AB, JRBP, LAL, CL, NJW, RAS); Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (KTN); Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK (DJT, DFE, PDPP); Queensland Institute of Medical Research, Brisbane, Australia (JNP, ANECS, TO, ABS); University of Cambridge Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, Cambridge, UK (DBS, RKS); Hunter Medical Research Institute, John Hunter Hospital, Newcastle, Australia (JA, EH, RJS); Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, The University of Newcastle, Newcastle, Australia (JA, MM); Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK (AMD, DFE, PDPP); Centre for Information Based Medicine, School of Medicine and Public Health, University of Newcastle, Australia (EH, RJS).
Douglas F EastonMRC Epidemiology Unit, University of Cambridge, Cambridge, UK (KTN, SJS, AB, JRBP, LAL, CL, NJW, RAS); Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (KTN); Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK (DJT, DFE, PDPP); Queensland Institute of Medical Research, Brisbane, Australia (JNP, ANECS, TO, ABS); University of Cambridge Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, Cambridge, UK (DBS, RKS); Hunter Medical Research Institute, John Hunter Hospital, Newcastle, Australia (JA, EH, RJS); Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, The University of Newcastle, Newcastle, Australia (JA, MM); Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK (AMD, DFE, PDPP); Centre for Information Based Medicine, School of Medicine and Public Health, University of Newcastle, Australia (EH, RJS).
Elizabeth HollidayMRC Epidemiology Unit, University of Cambridge, Cambridge, UK (KTN, SJS, AB, JRBP, LAL, CL, NJW, RAS); Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (KTN); Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK (DJT, DFE, PDPP); Queensland Institute of Medical Research, Brisbane, Australia (JNP, ANECS, TO, ABS); University of Cambridge Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, Cambridge, UK (DBS, RKS); Hunter Medical Research Institute, John Hunter Hospital, Newcastle, Australia (JA, EH, RJS); Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, The University of Newcastle, Newcastle, Australia (JA, MM); Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK (AMD, DFE, PDPP); Centre for Information Based Medicine, School of Medicine and Public Health, University of Newcastle, Australia (EH, RJS).
Luca A LottaMRC Epidemiology Unit, University of Cambridge, Cambridge, UK (KTN, SJS, AB, JRBP, LAL, CL, NJW, RAS); Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (KTN); Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK (DJT, DFE, PDPP); Queensland Institute of Medical Research, Brisbane, Australia (JNP, ANECS, TO, ABS); University of Cambridge Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, Cambridge, UK (DBS, RKS); Hunter Medical Research Institute, John Hunter Hospital, Newcastle, Australia (JA, EH, RJS); Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, The University of Newcastle, Newcastle, Australia (JA, MM); Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK (AMD, DFE, PDPP); Centre for Information Based Medicine, School of Medicine and Public Health, University of Newcastle, Australia (EH, RJS).
Tracy O'MaraMRC Epidemiology Unit, University of Cambridge, Cambridge, UK (KTN, SJS, AB, JRBP, LAL, CL, NJW, RAS); Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (KTN); Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK (DJT, DFE, PDPP); Queensland Institute of Medical Research, Brisbane, Australia (JNP, ANECS, TO, ABS); University of Cambridge Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, Cambridge, UK (DBS, RKS); Hunter Medical Research Institute, John Hunter Hospital, Newcastle, Australia (JA, EH, RJS); Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, The University of Newcastle, Newcastle, Australia (JA, MM); Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK (AMD, DFE, PDPP); Centre for Information Based Medicine, School of Medicine and Public Health, University of Newcastle, Australia (EH, RJS).
Mark McEvoyMRC Epidemiology Unit, University of Cambridge, Cambridge, UK (KTN, SJS, AB, JRBP, LAL, CL, NJW, RAS); Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (KTN); Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK (DJT, DFE, PDPP); Queensland Institute of Medical Research, Brisbane, Australia (JNP, ANECS, TO, ABS); University of Cambridge Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, Cambridge, UK (DBS, RKS); Hunter Medical Research Institute, John Hunter Hospital, Newcastle, Australia (JA, EH, RJS); Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, The University of Newcastle, Newcastle, Australia (JA, MM); Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK (AMD, DFE, PDPP); Centre for Information Based Medicine, School of Medicine and Public Health, University of Newcastle, Australia (EH, RJS).
Paul D P PharoahMRC Epidemiology Unit, University of Cambridge, Cambridge, UK (KTN, SJS, AB, JRBP, LAL, CL, NJW, RAS); Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (KTN); Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK (DJT, DFE, PDPP); Queensland Institute of Medical Research, Brisbane, Australia (JNP, ANECS, TO, ABS); University of Cambridge Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, Cambridge, UK (DBS, RKS); Hunter Medical Research Institute, John Hunter Hospital, Newcastle, Australia (JA, EH, RJS); Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, The University of Newcastle, Newcastle, Australia (JA, MM); Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK (AMD, DFE, PDPP); Centre for Information Based Medicine, School of Medicine and Public Health, University of Newcastle, Australia (EH, RJS).
Rodney J ScottMRC Epidemiology Unit, University of Cambridge, Cambridge, UK (KTN, SJS, AB, JRBP, LAL, CL, NJW, RAS); Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (KTN); Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK (DJT, DFE, PDPP); Queensland Institute of Medical Research, Brisbane, Australia (JNP, ANECS, TO, ABS); University of Cambridge Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, Cambridge, UK (DBS, RKS); Hunter Medical Research Institute, John Hunter Hospital, Newcastle, Australia (JA, EH, RJS); Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, The University of Newcastle, Newcastle, Australia (JA, MM); Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK (AMD, DFE, PDPP); Centre for Information Based Medicine, School of Medicine and Public Health, University of Newcastle, Australia (EH, RJS).
Amanda B SpurdleMRC Epidemiology Unit, University of Cambridge, Cambridge, UK (KTN, SJS, AB, JRBP, LAL, CL, NJW, RAS); Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (KTN); Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK (DJT, DFE, PDPP); Queensland Institute of Medical Research, Brisbane, Australia (JNP, ANECS, TO, ABS); University of Cambridge Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, Cambridge, UK (DBS, RKS); Hunter Medical Research Institute, John Hunter Hospital, Newcastle, Australia (JA, EH, RJS); Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, The University of Newcastle, Newcastle, Australia (JA, MM); Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK (AMD, DFE, PDPP); Centre for Information Based Medicine, School of Medicine and Public Health, University of Newcastle, Australia (EH, RJS).
Claudia LangenbergMRC Epidemiology Unit, University of Cambridge, Cambridge, UK (KTN, SJS, AB, JRBP, LAL, CL, NJW, RAS); Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (KTN); Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK (DJT, DFE, PDPP); Queensland Institute of Medical Research, Brisbane, Australia (JNP, ANECS, TO, ABS); University of Cambridge Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, Cambridge, UK (DBS, RKS); Hunter Medical Research Institute, John Hunter Hospital, Newcastle, Australia (JA, EH, RJS); Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, The University of Newcastle, Newcastle, Australia (JA, MM); Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK (AMD, DFE, PDPP); Centre for Information Based Medicine, School of Medicine and Public Health, University of Newcastle, Australia (EH, RJS).
Nicholas J WarehamMRC Epidemiology Unit, University of Cambridge, Cambridge, UK (KTN, SJS, AB, JRBP, LAL, CL, NJW, RAS); Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (KTN); Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK (DJT, DFE, PDPP); Queensland Institute of Medical Research, Brisbane, Australia (JNP, ANECS, TO, ABS); University of Cambridge Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, Cambridge, UK (DBS, RKS); Hunter Medical Research Institute, John Hunter Hospital, Newcastle, Australia (JA, EH, RJS); Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, The University of Newcastle, Newcastle, Australia (JA, MM); Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK (AMD, DFE, PDPP); Centre for Information Based Medicine, School of Medicine and Public Health, University of Newcastle, Australia (EH, RJS).
Robert A ScottMRC Epidemiology Unit, University of Cambridge, Cambridge, UK (KTN, SJS, AB, JRBP, LAL, CL, NJW, RAS); Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (KTN); Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK (DJT, DFE, PDPP); Queensland Institute of Medical Research, Brisbane, Australia (JNP, ANECS, TO, ABS); University of Cambridge Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, Cambridge, UK (DBS, RKS); Hunter Medical Research Institute, John Hunter Hospital, Newcastle, Australia (JA, EH, RJS); Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, The University of Newcastle, Newcastle, Australia (JA, MM); Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK (AMD, DFE, PDPP); Centre for Information Based Medicine, School of Medicine and Public Health, University of Newcastle, Australia (EH, RJS). robert.scott@mrc-epid.cam.ac.uk.
John Hunter Hospital · AUHunter Medical Research Institute · AUMRC Epidemiology Unit · GBMedical Research Council · GBQIMR Berghofer Medical Research Institute · AUUniversity of Cambridge · GBWellcome Trust · GBUniversity of Newcastle Australia · AUUniversity of Pennsylvania · USWellcome/MRC Institute of Metabolic Science · GB

Funding

Cancer Research UK 10119Cancer Research UK 10124Cancer Research UK 16561Cancer Research UK 16563Cancer Research UK 16565Cancer Research UK C490/A10124Medical Research Council G0000934Medical Research Council MC_U106179471Medical Research Council MC_U106179472Medical Research Council MC_UU_12015/1Medical Research Council MC_UU_12015/2Wellcome Trust 068545/Z/02Wellcome Trust 085475Wellcome Trust 098498Wellcome Trust 100574
6 · The paper itself

Abstract

backgroundInsulinemia and type 2 diabetes (T2D) have been associated with endometrial cancer risk in numerous observational studies. However, the causality of these associations is uncertain. Here we use a Mendelian randomization (MR) approach to assess whether insulinemia and T2D are causally associated with endometrial cancer.

methodsWe used single nucleotide polymorphisms (SNPs) associated with T2D (49 variants), fasting glucose (36 variants), fasting insulin (18 variants), early insulin secretion (17 variants), and body mass index (BMI) (32 variants) as instrumental variables in MR analyses. We calculated MR estimates for each risk factor with endometrial cancer using an inverse-variance weighted method with SNP-endometrial cancer associations from 1287 case patients and 8273 control participants.

resultsGenetically predicted higher fasting insulin levels were associated with greater risk of endometrial cancer (odds ratio [OR] per standard deviation = 2.34, 95% confidence internal [CI] = 1.06 to 5.14, P = .03). Consistently, genetically predicted higher 30-minute postchallenge insulin levels were also associated with endometrial cancer risk (OR = 1.40, 95% CI = 1.12 to 1.76, P = .003). We observed no associations between genetic risk of type 2 diabetes (OR = 0.91, 95% CI = 0.79 to 1.04, P = .16) or higher fasting glucose (OR = 1.00, 95% CI = 0.67 to 1.50, P = .99) and endometrial cancer. In contrast, endometrial cancer risk was higher in individuals with genetically predicted higher BMI (OR = 3.86, 95% CI = 2.24 to 6.64, P = 1.2x10(-6)).

conclusionThis study provides evidence to support a causal association of higher insulin levels, independently of BMI, with endometrial cancer risk.

Indexed as

Polymorphism, Single NucleotideAdultAgedBlood GlucoseBody Mass IndexDiabetes Mellitus, Type 2Endometrial NeoplasmsFastingFemaleGenotypeHumansHyperinsulinismInsulinMendelian Randomization AnalysisMiddle AgedOdds RatioBlood GlucoseInsulin

Identifiers

PMID26134033
PMCPMC4572886
OpenAlexW2186857284

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