Evidence map›Paper›PMID 25082786›Full record

SynthesisHaematologica2014

MDM2 promotor polymorphism and disease characteristics in chronic lymphocytic leukemia: results of an individual patient data-based meta-analysis.

Axel Benner, Larry Mansouri, Davide Rossi, Aneela Majid, Kerstin Willander, Anton Parker, Gareth Bond, Sarka Pavlova, Holger Nückel, Olaf Merkel and 17 more

Open access · goldAbstract readMeta-Analysis
In one paragraph

Synthesis in Haematologica, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact, top 85% 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

2 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
  2. Article
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

27 authors at 17 institutions in 8 countries.

Axel BennerDivision of Biostatistics, German Cancer Research Center, Heidelberg, Germany.
Larry MansouriDepartment of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Sweden.
Davide RossiDivision of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy.
Aneela MajidDepartment of Cancer Studies and Molecular Medicine, MRC Toxicology Unit, University of Leicester, UK.
Kerstin WillanderDepartment of Clinical and Experimental Medicine, Linköping University, Sweden.
Anton ParkerDepartment of Hematology, Royal Bournemouth Hospital, UK.
Gareth BondLudwig Institute for Cancer Research, University of Oxford, UK.
Sarka PavlovaUniversity Hospital Brno and Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
Holger NückelDepartment of Hematology, University Hospital, University of Duisburg-Essen, Essen, Germany.
Olaf MerkelLaboratory for Immunological and Molecular Cancer Research, University Clinics of Internal Medicine III with Hematology, Oncology, Hemostaseology, Infectious Disease and Rheumatology, Oncologic Center, Paracelus Medical University, Salzburg, Austria.
Paolo GhiaLaboratory of B Cell Neoplasia, Division of Molecular Oncology, Ospedale San Raffaele, Istituto Scientifico San Raffale, Fondazione Centro San Raffaele, Università Bita-Salute San Raffaele, Milan, Italy.
Emili MontserratInstitute of Hematology and Oncology, Department of Hematology, Hospital Clínic, IDIBAPS, University of Barcelona, Spain.
Mohd Arifin KaderiDepartment of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Sweden Department of Biomedical Sciences, Kull Allied Health Sciences, International Islamic University Malaysia, Kuantan, Pahang, Malaysia.
Richard RosenquistDepartment of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Sweden.
Gianluca GaidanoDivision of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy.
Martin J S DyerDepartment of Cancer Studies and Molecular Medicine, MRC Toxicology Unit, University of Leicester, UK.
Peter SöderkvistDepartment of Clinical and Experimental Medicine, Linköping University, Sweden.
Mats LinderholmDepartment of Clinical and Experimental Medicine, Linköping University, Sweden.
David OscierDepartment of Hematology, Royal Bournemouth Hospital, UK.
Zuzana TvaruzkovaUniversity Hospital Brno and Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
Sarka PospisilovaUniversity Hospital Brno and Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
Ulrich DührsenDepartment of Hematology, University Hospital, University of Duisburg-Essen, Essen, Germany.
Richard GreilLaboratory for Immunological and Molecular Cancer Research, University Clinics of Internal Medicine III with Hematology, Oncology, Hemostaseology, Infectious Disease and Rheumatology, Oncologic Center, Paracelus Medical University, Salzburg, Austria.
Hartmut DöhnerDepartment of Internal Medicine III, University of Ulm, Germany.
Stephan StilgenbauerDepartment of Internal Medicine III, University of Ulm, Germany.
Thorsten ZenzDepartment of Translational Oncology, National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Heidelberg, Germany Department of Internal Medicine V, University Hospital Heidelberg, Germany thorsten.zenz@nct-heidelberg.de.
European Research Initiative on CLL (ERIC)
Linköping University · SEParacelsus Medical University · ATRoyal Bournemouth Hospital · GBScience for Life Laboratory · SEUniversità degli Studi del Piemonte Orientale “Amedeo Avogadro” · ITUniversität Ulm · DEUniversity Hospital Brno · CZUniversity of Duisburg-Essen · DECentral European Institute of Technology · CZConsorci Institut D'Investigacions Biomediques August Pi I Sunyer · ESGerman Cancer Research Center · DEHeidelberg University · DEIRCCS Ospedale San Raffaele · ITLudwig Cancer Research · GBMRC Toxicology Unit · GBUniversity of Leicester · GBUppsala University · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

A number of single nucleotide polymorphisms have been associated with disease predisposition in chronic lymphocytic leukemia. A single nucleotide polymorphism in the MDM2 promotor region, MDM2SNP309, was shown to soothe the p53 pathway. In the current study, we aimed to clarify the effect of the MDM2SNP309 on chronic lymphocytic leukemia characteristics and outcome. We performed a meta-analysis of data from 2598 individual patients from 10 different cohorts. Patients' data and genetic analysis for MDM2SNP309 genotype, immunoglobulin heavy chain variable region mutation status and fluorescence in situ hybridization results were collected. There were no differences in overall survival based on the polymorphism (log rank test, stratified by study cohort; P=0.76; GG genotype: cohort-adjusted median overall survival of 151 months; TG: 153 months; TT: 149 months). In a multivariable Cox proportional hazards regression analysis, advanced age, male sex and unmutated immunoglobulin heavy chain variable region genes were associated with inferior survival, but not the MDM2 genotype. The MDM2SNP309 is unlikely to influence disease characteristics and prognosis in chronic lymphocytic leukemia. Studies investigating the impact of individual single nucleotide polymorphisms on prognosis are often controversial. This may be due to selection bias and small sample size. A meta-analysis based on individual patient data provides a reasonable strategy for prognostic factor analyses in the case of small individual studies. Individual patient data-based meta-analysis can, therefore, be a powerful tool to assess genetic risk factors in the absence of large studies.

Indexed as

Databases, FactualAdultAgedAged, 80 and overCohort StudiesFemaleHumansLeukemia, Lymphocytic, Chronic, B-CellMaleMiddle AgedPolymorphism, Single NucleotidePromoter Regions, GeneticProto-Oncogene Proteins c-mdm2Young AdultMDM2 protein, humanProto-Oncogene Proteins c-mdm2

Identifiers

PMID25082786
PMCPMC4116826
OpenAlexW2151723026

What OpenQuestion holds

Textmetadata
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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.