Evidence map›Paper›PMID 27259051›Full record

ArticleAmerican journal of human genetics2016

A Common Variant at the 14q32 Endometrial Cancer Risk Locus Activates AKT1 through YY1 Binding.

Jodie N Painter, Susanne Kaufmann, Tracy A O'Mara, Kristine M Hillman, Haran Sivakumaran, Hatef Darabi, Timothy H T Cheng, John Pearson, Stephen Kazakoff, Nicola Waddell and 12 more

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

Article in American journal of human genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 2 pooled it
0.8field-weighted citation impact, top 28% 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

21 citing papers in PubMed, 2 syntheses or guidelines pooled it, 30 citations in OpenAlex.

  1. Pooled it
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  7. SDC4-rs1981429 and ATM-rs228590 may provide early biomarkers of breast cancer risk.Journal of cancer research and clinical oncology · 2023
    Article
  8. Article
  9. Alternative splicing ofJournal of gynecologic oncology · 2023
    Article
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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

22 authors at 9 institutions in 5 countries.

Jodie N PainterQIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia.
Susanne KaufmannQIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia.
Tracy A O'MaraQIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia.
Kristine M HillmanQIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia.
Haran SivakumaranQIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia.
Hatef DarabiDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 17177, Sweden.
Timothy H T ChengWellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
John PearsonQIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia.
Stephen KazakoffQIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia.
Nicola WaddellQIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia.
Erling A HoivikCentre for Cancer Biomarkers, Department of Clinical Science, The University of Bergen, N5020 Bergen, Norway; Department of Obstetrics and Gynecology, Haukeland University Hospital, N5021 Bergen, Norway.
Ellen L GoodeDepartment of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA.
Rodney J ScottHunter Medical Research Institute, John Hunter Hospital, Newcastle, NSW 2305, Australia; Pathology North (Newcastle) John Hunter Hospital, Newcastle, NSW 2305, Australia; Centre for Information Based Medicine, University of Newcastle, NSW 2308, Australia; School of Biomedical Sciences and Pharmacy, University of Newcastle, NSW 2308, Australia.
Ian TomlinsonWellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
Alison M DunningCentre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge CB1 8RN, UK.
Douglas F EastonCentre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge CB1 8RN, UK; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
Juliet D FrenchQIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia.
Helga B SalvesenCentre for Cancer Biomarkers, Department of Clinical Science, The University of Bergen, N5020 Bergen, Norway; Department of Obstetrics and Gynecology, Haukeland University Hospital, N5021 Bergen, Norway.
Pamela M PollockInstitute of Health and Biomedical Innovation and School of Biomedical Science, Queensland University of Technology at the Translation Research Institute, Brisbane 4102, Australia.
Deborah J ThompsonCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
Amanda B SpurdleQIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia.
Stacey L EdwardsQIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia. Electronic address: stacey.edwards@qimrberghofer.edu.au.
QIMR Berghofer Medical Research Institute · AUUniversity of Cambridge · GBCentre for Human Genetics · GBHaukeland University Hospital · NOJohn Hunter Hospital · AUKarolinska Institutet · SEMayo Clinic in Florida · USTranslational Research Institute · AUUniversity of Bergen · NO

Funding

Cancer Research UK 16565Wellcome TrustWellcome Trust 090532/Z/09/Z
6 · The paper itself

Abstract

A recent meta-analysis of multiple genome-wide association and follow-up endometrial cancer case-control datasets identified a novel genetic risk locus for this disease at chromosome 14q32.33. To prioritize the functional SNP(s) and target gene(s) at this locus, we employed an in silico fine-mapping approach using genotyped and imputed SNP data for 6,608 endometrial cancer cases and 37,925 controls of European ancestry. Association and functional analyses provide evidence that the best candidate causal SNP is rs2494737. Multiple experimental analyses show that SNP rs2494737 maps to a silencer element located within AKT1, a member of the PI3K/AKT/MTOR intracellular signaling pathway activated in endometrial tumors. The rs2494737 risk A allele creates a YY1 transcription factor-binding site and abrogates the silencer activity in luciferase assays, an effect mimicked by transfection of YY1 siRNA. Our findings suggest YY1 is a positive regulator of AKT1, mediating the stimulatory effects of rs2494737 increasing endometrial cancer risk. Identification of an endometrial cancer risk allele within a member of the PI3K/AKT signaling pathway, more commonly activated in tumors by somatic alterations, raises the possibility that well tolerated inhibitors targeting this pathway could be candidates for evaluation as chemopreventive agents in individuals at high risk of developing endometrial cancer.

Indexed as

Chromosomes, Human, Pair 14Endometrial NeoplasmsFemaleGenetic LociGenetic Predisposition to DiseaseGenome-Wide Association StudyGenotypeHumansPhosphatidylinositol 3-KinasesPolymorphism, Single NucleotideProtein BindingProto-Oncogene Proteins c-aktRisk FactorsSignal TransductionUterine NeoplasmsYY1 Transcription FactorAKT1 protein, humanPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktYY1 protein, humanYY1 Transcription Factor

Identifiers

PMID27259051
PMCPMC4908177
OpenAlexW2406780350

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.