Evidence map›Paper›PMID 35740506›Full record

ArticleCancers2022

Genome-Wide Meta-Analysis Identifies Variants in

Meta H M Diekstra, Jesse J Swen, Loes F M van der Zanden, Sita H Vermeulen, Epie Boven, Ron H J Mathijssen, Koya Fukunaga, Taisei Mushiroda, Fumiya Hongo, Egbert Oosterwijk and 16 more

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
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

5 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
  2. Retrospective study assessing the role of the androgen receptor in clear cell renal cell cancer patients treated with VEGFR inhibitors in monotherapy.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025
    Article
  3. Article
  4. Article
  5. 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

26 authors at 16 institutions in 9 countries.

Meta H M DiekstraDepartment of Pharmacology, Princess Maxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands.ORCID 0000-0002-9368-3650
Jesse J SwenDepartment of Clinical Pharmacy and Toxicology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.ORCID 0000-0002-3965-5552
Loes F M van der ZandenRadboud University Medical Center, 6525 GA Nijmegen, The Netherlands.ORCID 0000-0003-3914-7491
Sita H VermeulenRadboud University Medical Center, 6525 GA Nijmegen, The Netherlands.
Epie BovenDepartment of Medical Oncology, Amsterdam UMC, Vrije Universiteit Amsterdam/Cancer Center Amsterdam, 1081 HV Amsterdam, The Netherlands.
Ron H J MathijssenDepartment of Medical Oncology, Erasmus MC Cancer Institute, 3015 GD Rotterdam, The Netherlands.ORCID 0000-0001-5667-5697
Koya FukunagaCore for Genomic Medicine, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.
Taisei MushirodaCore for Genomic Medicine, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.
Fumiya HongoDepartment of Urology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
Egbert OosterwijkRadboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.
Anne Cambon-ThomsenCERPOP, Center of Epidemiology and Research in Population Health, Joint Unit 1295, Institut National de la Santé et de la Recherche Médicale (Inserm), Faculty of Medicine, Université de Toulouse, Université Toulouse III-Paul Sabatier, CEDEX, 31062 Toulouse, France.ORCID 0000-0001-8793-3644
Daniel CastellanoMedical Oncology Department, I+12 Research Institute, (CiberOnc), Hospital Universitario 12 de Octubre, 28041 Madrid, Spain.
Achim FritschInstitute of Pharmacy, Clinical Pharmacy, University of Bonn, 53117 Bonn, Germany.
Jesus Garcia DonasMedical Oncology, HM Hospitales-Centro Integral Oncológico HM Clara Campal, 28050 Madrid, Spain.
Cristina Rodriguez-AntonaHereditary Endorine Cancer Group, Spanish National Cancer Research Center (CNIO) and Biomedical Network on Rare Diseases (CIBERER), 28029 Madrid, Spain.
Rob RuijtenbeekPamGene International B.V., 5211 HH 's-Hertogenbosch, The Netherlands.
Marius T RaduUniversity of Medicine and Pharmacy Carol Davila, 050474 Bucharest, Romania.
Tim EisenDepartment of Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge CB2 0SL, UK.ORCID 0000-0001-9663-4873
Kerstin JunkerClinic of Urology and Paediatric Urology, Saarland University, 66424 Homburg, Germany.
Max RoesslerCESAR Central Office, CESAR Central European Society for Anticancer Drug Research-EWIV, 1010 Vienna, Austria.
Ulrich JaehdeInstitute of Pharmacy, Clinical Pharmacy, University of Bonn, 53117 Bonn, Germany.
Tsuneharu MikiDepartment of Urology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
Stefan BöhringerDepartment of Clinical Pharmacy and Toxicology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
Michiaki KuboCore for Genomic Medicine, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.
Lambertus A L M KiemeneyRadboud University Medical Center, 6525 GA Nijmegen, The Netherlands.
Henk-Jan GuchelaarDepartment of Clinical Pharmacy and Toxicology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.ORCID 0000-0002-7085-1383
Leiden University Medical Center · NLRadboud University Nijmegen · NLRIKEN Center for Integrative Medical Sciences · JPKyoto Prefectural University of Medicine · JPUniversity of Bonn · DEAmsterdam University Medical Centers · NLCambridge University Hospitals NHS Foundation Trust · GBCarol Davila University of Medicine and Pharmacy · ROCentral European Society for Anticancer Drug Research · ATCentre for Biomedical Network Research on Rare Diseases · ESErasmus MC Cancer Institute · NLHM Hospitales · ESHospital Universitario 12 De Octubre · ESPamGene (Netherlands) · NLSaarland University · DEUniversité Toulouse III - Paul Sabatier · FR

Funding

European Union's Seventh Framework Programme (FP7/2007-2013) 259939
6 · The paper itself

Abstract

Individual response to sunitinib in metastatic renal cell carcinoma (mRCC) patients is highly variable. Earlier, sunitinib outcome was related to single nucleotide polymorphisms (SNPs) in CYP3A5 and ABCB1. Our aim is to provide novel insights into biological mechanisms underlying sunitinib action. We included mRCC patients from the European EuroTARGET consortium (n = 550) and the RIKEN cohort in Japan (n = 204) which were analysed separately and in a meta-analysis of genome-wide association studies (GWAS). SNPs were tested for association with progression-free survival (PFS) and overall survival (OS) using Cox regression. Summary statistics were combined using a fixed effect meta-analysis. SNP rs28520013 in PDLIM3 and the correlated SNPs rs2205096 and rs111356738 both in DSCAM, showed genome-wide significance (p < 5 × 10−8) with PFS and OS in the meta-analysis. The variant T-allele of rs28520013 associated with an inferior PFS of 5.1 months compared to 12.5 months in non-carriers (p = 4.02 × 10−10, HR = 7.26). T-allele carriers of rs28520013 showed an inferior OS of 6.9 months versus 30.2 months in non-carriers (p = 1.62 × 10−8, HR = 5.96). In this GWAS we identified novel genetic variants in PDLIM3 and DSCAM that impact PFS and OS in mRCC patients receiving sunitinib. The underlying link between the identified genes and the molecular mechanisms of sunitinib action needs to be elucidated.

Indexed as

clear cell renal cell carcinomagenome wide association studymetastatic renal cell carcinomapharmacogeneticssingle nucleotide polymorphismsunitinib

Identifiers

PMID35740506
PMCPMC9220885
OpenAlexW4281814030

What OpenQuestion 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 OpenQuestion graph.