Evidence map›Paper›PMID 28179588›Full record

ArticleOncotarget2017

TP53-based interaction analysis identifies cis-eQTL variants for TP53BP2, FBXO28, and FAM53A that associate with survival and treatment outcome in breast cancer.

Rainer Fagerholm, Sofia Khan, Marjanka K Schmidt, Montserrat García-Closas, Päivi Heikkilä, Jani Saarela, Jonathan Beesley, Maral Jamshidi, Kristiina Aittomäki, Jianjun Liu and 43 more

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

Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.6field-weighted citation impact, top 31% 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

7 citing papers in PubMed, 11 citations in OpenAlex.

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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

53 authors at 20 institutions in 11 countries.

Rainer FagerholmDepartment of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
Sofia KhanDepartment of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
Marjanka K SchmidtNetherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
Montserrat García-ClosasDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Päivi HeikkiläDepartment of Pathology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
Jani SaarelaInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland.
Jonathan BeesleyDepartment of Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Maral JamshidiDepartment of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
Kristiina AittomäkiDepartment of Clinical Genetics, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
Jianjun LiuHuman Genetics Division, Genome Institute of Singapore, Singapore, Singapore.
H Raza AliCancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, UK.
Irene L AndrulisLunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Canada.
Matthias W BeckmannDepartment of Gynaecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany.
Sabine BehrensDivision of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Fiona M BlowsCentre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
Hermann BrennerDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Jenny Chang-ClaudeDivision of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Fergus J CouchDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Kamila CzeneDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Peter A FaschingDepartment of Gynaecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany.
Jonine FigueroaUsher Institute of Population Health Sciences and Informatics, The University of Edinburgh Medical School, Edinburgh, UK.
Giuseppe FlorisLeuven Multidisciplinary Breast Center, Department of Oncology, KULeuven, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium.
Gord GlendonLunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Canada.
Qi GuoCentre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
Per HallDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Emily HallbergDepartment of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
Ute HamannMolecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Bernd HolleczekSaarland Cancer Registry, Saarbrücken, Germany.
Maartje J HooningDepartment of Medical Oncology, Family Cancer Clinic, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
John L HopperCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global health, The University of Melbourne, Melbourne, Australia.
Agnes JagerDepartment of Medical Oncology, Family Cancer Clinic, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
Maria KabischMolecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
kConFab/AOCS InvestigatorsPeter MacCallum Cancer Center, The University of Melbourne, Melbourne, Australia.
Renske KeemanNetherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
Veli-Matti KosmaCancer Center of Eastern Finland, University of Eastern Finland, Kuopio, Finland.
Diether LambrechtsVesalius Research Center, VIB, Leuven, Belgium.
Annika LindblomDepartment of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Arto MannermaaCancer Center of Eastern Finland, University of Eastern Finland, Kuopio, Finland.
Sara MargolinDepartment of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Elena ProvenzanoDepartment of Oncology, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
Mitul ShahCentre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
Melissa C SoutheyDepartment of Pathology, The University of Melbourne, Melbourne, Australia.
Joe DennisCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Michael LushCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Kyriaki MichailidouCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Qin WangCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Manjeet K BollaCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Alison M DunningCentre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
Douglas F EastonCentre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
Paul D P PharoahCentre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
Georgia Chenevix-TrenchDepartment of Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Carl BlomqvistDepartment of Oncology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
Heli NevanlinnaDepartment of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
University of Cambridge · GBUniversity of Helsinki · FIGerman Cancer Research Center · DEKarolinska Institutet · SEThe University of Melbourne · AUErasmus MC Cancer Institute · NLInternational Paper (United States) · USMount Sinai Hospital · CANational Cancer Institute · USQIMR Berghofer Medical Research Institute · AUThe Netherlands Cancer Institute · NLUniversity of Eastern Finland · FIGenome Institute of Singapore · SGKrebsregister Saarland · DEKU Leuven · BEMayo Clinic in Arizona · USUniversität Hamburg · DEUniversitätsklinikum Erlangen · DEUniversity of California, Los Angeles · USVIB-KU Leuven Center for Cancer Biology · BE

Funding

Hormone-Related CancersZIACP010126 · NCI · DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS · PI GIERACH, GRETCHEN · 2009 to 2025
$103.5M
The Role of CHFR in Tumorigenesis and Paclitaxel-Sensitivity in Breast CancerP50CA116201 · NCI · MAYO CLINIC ROCHESTER · PI Fergus Joseph Couch · 2005 to 2026
$49.9M
Breast Cancer Family Registry CohortUM1CA164920 · NCI · CANCER PREVENTION INSTIT OF CALIFORNIA · PI ANDRULIS, IRENE, BUYS, SAUNDRA S · 2012 to 2017
$12.7M
Epidemiologic StudiesU19CA148065 · NCI · HARVARD SCHOOL OF PUBLIC HEALTH · PI AHSAN, HABIBUL, BRUGGE, JOAN SIEFERT · 2010 to 2014
$10.6M
Epidemiological and Clinical Translational Studies Post Genome-Wide AssociationU19CA148537 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI EASTON, DOUGLAS FREDERICK, EELES, ROSALIND · 2010 to 2014
$10.4M
Ovarian cancer GWAS discovery, expansion and replication (N2 - Project #1)U19CA148112 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI SELLERS, THOMAS A · 2010 to 2014
$10.2M
Risk and penetrance of mutations from breast cancer testing panels.R01CA192393 · NCI · MAYO CLINIC ROCHESTER · PI COUCH, FERGUS JOSEPH, NATHANSON, KATHERINE L. · 2014 to 2018
$6.3M
A genome-wide association study for breast cancer in BRCA1 mutation carriersR01CA128978 · NCI · MAYO CLINIC ROCHESTER · PI COUCH, FERGUS JOSEPH · 2008 to 2012
$4.8M
Identifying and validating novel susceptibility genes for breast cancerR01CA176785 · NCI · MAYO CLINIC ROCHESTER · PI COUCH, FERGUS JOSEPH, NATHANSON, KATHERINE L. · 2014 to 2018
$3.4M
BRCA2 missense mutations and breast cancerR01CA116167 · NCI · MAYO CLINIC ROCHESTER · PI COUCH, FERGUS JOSEPH · 2007 to 2011
$3.0M
BRCA1 and BRCA2 missense mutations and breast cancer riskU01CA116167 · NCI · MAYO CLINIC ROCHESTER · PI COUCH, FERGUS JOSEPH · 2013 to 2017
$2.7M
Cancer Research UK 10118Cancer Research UK 10124Cancer Research UK 16561Cancer Research UK 16565NCI NIH HHS P50 CA116201NCI NIH HHS R01 CA116167NCI NIH HHS R01 CA128978NCI NIH HHS R01 CA176785NCI NIH HHS R01 CA192393NCI NIH HHS U01 CA116167NCI NIH HHS U19 CA148065NCI NIH HHS U19 CA148112NCI NIH HHS U19 CA148537NCI NIH HHS UM1 CA164920
6 · The paper itself

Abstract

TP53 overexpression is indicative of somatic TP53 mutations and associates with aggressive tumors and poor prognosis in breast cancer. We utilized a two-stage SNP association study to detect variants associated with breast cancer survival in a TP53-dependent manner. Initially, a genome-wide study (n = 575 cases) was conducted to discover candidate SNPs for genotyping and validation in the Breast Cancer Association Consortium (BCAC). The SNPs were then tested for interaction with tumor TP53 status (n = 4,610) and anthracycline treatment (n = 17,828). For SNPs interacting with anthracycline treatment, siRNA knockdown experiments were carried out to validate candidate genes.In the test for interaction between SNP genotype and TP53 status, we identified one locus, represented by rs10916264 (p(interaction) = 3.44 × 10-5; FDR-adjusted p = 0.0011) in estrogen receptor (ER) positive cases. The rs10916264 AA genotype associated with worse survival among cases with ER-positive, TP53-positive tumors (hazard ratio [HR] 2.36, 95% confidence interval [C.I] 1.45 - 3.82). This is a cis-eQTL locus for FBXO28 and TP53BP2; expression levels of these genes were associated with patient survival specifically in ER-positive, TP53-mutated tumors. Additionally, the SNP rs798755 was associated with survival in interaction with anthracycline treatment (p(interaction) = 9.57 × 10-5, FDR-adjusted p = 0.0130). RNAi-based depletion of a predicted regulatory target gene, FAM53A, indicated that this gene can modulate doxorubicin sensitivity in breast cancer cell lines.If confirmed in independent data sets, these results may be of clinical relevance in the development of prognostic and predictive marker panels for breast cancer.

Indexed as

Quantitative Trait LociAdultAgedAged, 80 and overAnthracyclinesApoptosis Regulatory ProteinsBreast NeoplasmsFemaleGenotypeHumansMiddle AgedPolymorphism, Single NucleotideSKP Cullin F-Box Protein LigasesSurvival AnalysisTreatment OutcomeTumor Suppressor Protein p53AnthracyclinesApoptosis Regulatory ProteinsFBXO28 protein, humanSKP Cullin F-Box Protein LigasesTP53BP2 protein, humanTP53 protein, humanTumor Suppressor Protein p53anthracyclinebreast cancerSNPsurvivalTP53

Identifiers

PMID28179588
PMCPMC5392336
OpenAlexW2586470160

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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.