ArticleOncotarget2015
SNP-SNP interaction analysis of NF-κB signaling pathway on breast cancer survival.
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Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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13citing papers in PubMed, 1 pooled it
1.2field-weighted citation impact, top 23% of its field
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- Genome-wide association study of germline variants and breast cancer-specific mortality.British journal of cancer · 2019Pooled it
- Immunomodulatory Drugs Alter the Metabolism and the Extracellular Release of Soluble Mediators by Normal Monocytes.Molecules (Basel, Switzerland) · 2020Article
- SNPs in lncRNA Regions and Breast Cancer Risk.Frontiers in genetics · 2020Article
- Association of Genetic Variants in NF-kB with Susceptibility to Breast Cancer: a Case Control Study.Pathology oncology research : POR · 2019Article
- Update Breast Cancer 2019 Part 4 - Diagnostic and Therapeutic Challenges of New, Personalised Therapies for Patients with Early Breast Cancer.Geburtshilfe und Frauenheilkunde · 2019Article
- Investigation of the variants at the binding site of inflammatory transcription factor NF-κB in patients with end-stage renal disease.BMC nephrology · 2019Article
- Enriched power of disease-concordant twin-case-only design in detecting interactions in genome-wide association studies.European journal of human genetics : EJHG · 2019Article
- Risk, Prediction and Prevention of Hereditary Breast Cancer - Large-Scale Genomic Studies in Times of Big and Smart Data.Geburtshilfe und Frauenheilkunde · 2018Article
- Target therapy of TRIM-14 inhibits osteosarcoma aggressiveness through the nuclear factor-κB signaling pathway.Experimental and therapeutic medicine · 2018Article
- Bmi‑1‑targeting suppresses osteosarcoma aggressiveness through the NF‑κB signaling pathway.Molecular medicine reports · 2017Article
- SNP by SNP by environment interaction network of alcoholism.BMC systems biology · 2017Article
- SNP-SNP interactions as risk factors for aggressive prostate cancer.F1000Research · 2017Article
- Individual Differences in Social Behavior and Cortical Vasopressin Receptor: Genetics, Epigenetics, and Evolution.Frontiers in neuroscience · 2017Review
Corrections and comments
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Authors and funding
58 authors at 19 institutions in 10 countries.
Maral JamshidiDepartment of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, HUS, Finland.
Rainer FagerholmDepartment of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, HUS, Finland.
Sofia KhanDepartment of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, HUS, Finland.
Kristiina AittomäkiDepartment of Clinical Genetics, University of Helsinki and Helsinki University Hospital, Helsinki, HUS, Finland.
Kamila CzeneDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Hatef DarabiDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Jingmei LiDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Irene L AndrulisLunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON, Canada.
Jenny Chang-ClaudeDepartment of Obstetrics and Gynecology, University of Ulm, Ulm, Germany.
Peter DevileeDepartment of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
Peter A FaschingDepartment of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
Kyriaki MichailidouCentre 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.
Joe DennisCentre 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.
Qi GuoCentre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
Valerie RheniusCentre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
Sten CornelissenNetherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
Anja RudolphDivision of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Julia A KnightProsserman Centre for Health Research, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON, Canada.
Christian R LoehbergDepartment of Gynaecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany.
Barbara BurwinkelMolecular Epidemiology Group, German Cancer Research Center, Heidelberg, Germany.
Frederik MarmeDepartment of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany.
John L HopperCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
Melissa C SoutheyDepartment of Pathology, The University of Melbourne, Melbourne, Victoria, Australia.
Stig E BojesenFaculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Henrik FlygerDepartment of Breast Surgery, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark.
Hermann BrennerDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Bernd HolleczekSaarland Cancer Registry, Saarbrücken, Germany.
Sara MargolinDepartment of Oncology - Pathology, Karolinska Institutet, Stockholm, Sweden.
Arto MannermaaSchool of Medicine, Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland.
Veli-Matti KosmaSchool of Medicine, Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland.
kConFab Investigators
Laurien Van DyckVesalius Research Center (VRC), VIB, Leuven, Belgium.
Ines NevelsteenMultidisciplinary Breast Center, Medical Oncology, University Hospital Leuven, Leuven, Belgium.
Fergus J CouchDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Janet E OlsonDepartment of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
Graham G GilesCancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia.
Catriona McLeanAnatomical Pathology, The Alfred Hospital, Melbourne, Australia.
Christopher A HaimanDepartment of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Brian E HendersonDepartment of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Robert WinqvistLaboratory of Cancer Genetics and Tumor Biology, Cancer Research and Translational Medicine, Biocenter Oulu, University of Oulu, Oulu, Finland.
Katri PylkäsLaboratory of Cancer Genetics and Tumor Biology, Cancer Research and Translational Medicine, Biocenter Oulu, University of Oulu, Oulu, Finland.
Rob A E M TollenaarDepartment of Surgical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
Montserrat García-ClosasDivision of Genetics and Epidemiology, Institute of Cancer Research, Sutton, UK.
Jonine FigueroaDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Maartje J HooningDepartment of Medical Oncology, Erasmus MC Cancer Institute, AE Rotterdam, The Netherlands.
John W M MartensDepartment of Medical Oncology, Erasmus MC Cancer Institute, AE Rotterdam, The Netherlands.
Angela CoxSheffield Cancer Research, Department of Oncology, University of Sheffield, Sheffield, UK.
Simon S CrossAcademic Unit of Pathology, Department of Neuroscience, University of Sheffield, Sheffield, UK.
Jacques SimardCentre Hospitalier Universitaire de Québec Research Center, Laval University, Québec City, QC, Canada.
Alison M DunningCentre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
Douglas F EastonCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Paul D P PharoahCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Per HallDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Carl BlomqvistDepartment of Oncology, University of Helsinki and Helsinki University Central Hospital, Helsinki, HUS, Finland.
Marjanka K SchmidtNetherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
Heli NevanlinnaDepartment of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, HUS, Finland.
University of Cambridge · GBUniversity of Helsinki · FIGerman Cancer Research Center · DEThe University of Melbourne · AUMount Sinai Hospital · CAKarolinska Institutet · SEUniversity of Eastern Finland · FIUniversity of Southern California · USErasmus MC Cancer Institute · NLInstitute of Cancer Research · GBMayo Clinic in Arizona · USUniversity of California, Los Angeles · USUniversity of Copenhagen · DKCentre hospitalier universitaire de Québec · CAKU Leuven · BELeiden University Medical Center · NLNational Cancer Institute · USNordLab · FIUniversity of Sheffield · GB
Funding
Hormone-Related CancersZIACP010126 · NCI · DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS · PI GIERACH, GRETCHEN · 2009 to 2025
$103.5MThe Role of CHFR in Tumorigenesis and Paclitaxel-Sensitivity in Breast CancerP50CA116201 · NCI · MAYO CLINIC ROCHESTER · PI PETER C LUCAS · 2005 to 2026
$49.9MGENETIC SUSCEPTIBILITY TO CANCER IN MULTIETHNIC COHORTSR01CA063464 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HENDERSON, BRIAN E · 2001 to 2005
$23.2MMultiethnic Cohort Study of Diet and CancerR37CA054281 · NCI · UNIVERSITY OF HAWAII AT MANOA · PI KOLONEL, LAURENCE N. · 2003 to 2012
$23.2MCore-001U01CA164920 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Irene Andrulis, Sarah Violet Colonna · 2018 to 2026
$17.0MBreast Cancer Family Registry CohortUM1CA164920 · NCI · CANCER PREVENTION INSTIT OF CALIFORNIA · PI ANDRULIS, IRENE, BUYS, SAUNDRA S · 2012 to 2017
$12.7MCharacterizing Genetic Susceptibility to Breast and Prostate Cancer; the BPC3U01CA098758 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HENDERSON, BRIAN E · 2003 to 2010
$11.0MEpidemiologic StudiesU19CA148065 · NCI · HARVARD SCHOOL OF PUBLIC HEALTH · PI AHSAN, HABIBUL, BRUGGE, JOAN SIEFERT · 2010 to 2014
$10.6MEpidemiological and Clinical Translational Studies Post Genome-Wide AssociationU19CA148537 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI EASTON, DOUGLAS FREDERICK, EELES, ROSALIND · 2010 to 2014
$10.4MOvarian 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
$10.2MA genome-wide association study for breast cancer in BRCA1 mutation carriersR01CA128978 · NCI · MAYO CLINIC ROCHESTER · PI COUCH, FERGUS JOSEPH · 2008 to 2012
$4.8MMULTIETHNIC/MINORITY COHORT STUDY OF DIET AND CANCERR01CA054281 · NCI · UNIVERSITY OF HAWAII AT MANOA · PI KOLONEL, LAURENCE N. · 1993 to 2002
$4.5MCancer Research UK 10124Cancer Research UK 16561Cancer Research UK 16563Cancer Research UK 16565Cancer Research UK C12292/A11174Cancer Research UK C1281/A12014Cancer Research UK C1287/A10118Cancer Research UK C1287/A 10710Cancer Research UK C1287/A12014Cancer Research UK C5047/A10692Cancer Research UK C5047/A15007Cancer Research UK C5047/A8384Cancer Research UK C8197/A16565CIHRNCI NIH HHS 1U19 CA148065NCI NIH HHS 1U19 CA148112NCI NIH HHS 1U19 CA148537NCI NIH HHS CA116167NCI NIH HHS CA116201NCI NIH HHS CA128978NCI NIH HHS CA176785NCI NIH HHS P50 CA116201NCI NIH HHS R01 CA054281NCI NIH HHS R01 CA063464NCI NIH HHS R01 CA116167NCI NIH HHS R01 CA128978NCI NIH HHS R01 CA132839NCI NIH HHS R01 CA176785NCI NIH HHS R37 CA054281NCI NIH HHS U01 CA063464NCI NIH HHS U01 CA098758NCI NIH HHS U01 CA116167NCI NIH HHS U01 CA164920NCI NIH HHS U19 CA148065NCI NIH HHS U19 CA148112NCI NIH HHS U19 CA148537NCI NIH HHS UM1 CA164920
Abstract
In breast cancer, constitutive activation of NF-κB has been reported, however, the impact of genetic variation of the pathway on patient prognosis has been little studied. Furthermore, a combination of genetic variants, rather than single polymorphisms, may affect disease prognosis. Here, in an extensive dataset (n = 30,431) from the Breast Cancer Association Consortium, we investigated the association of 917 SNPs in 75 genes in the NF-κB pathway with breast cancer prognosis. We explored SNP-SNP interactions on survival using the likelihood-ratio test comparing multivariate Cox' regression models of SNP pairs without and with an interaction term. We found two interacting pairs associating with prognosis: patients simultaneously homozygous for the rare alleles of rs5996080 and rs7973914 had worse survival (HRinteraction 6.98, 95% CI=3.3-14.4, P=1.42E-07), and patients carrying at least one rare allele for rs17243893 and rs57890595 had better survival (HRinteraction 0.51, 95% CI=0.3-0.6, P = 2.19E-05). Based on in silico functional analyses and literature, we speculate that the rs5996080 and rs7973914 loci may affect the BAFFR and TNFR1/TNFR3 receptors and breast cancer survival, possibly by disturbing both the canonical and non-canonical NF-κB pathways or their dynamics, whereas, rs17243893-rs57890595 interaction on survival may be mediated through TRAF2-TRAIL-R4 interplay. These results warrant further validation and functional analyses.
Indexed as
Signal TransductionBiomarkers, TumorBreast NeoplasmsFemaleHumansNeoplasm GradingNeoplasm InvasivenessNeoplasm StagingNF-kappa BPolymorphism, Single NucleotidePrognosisSurvival RateBiomarkers, TumorNF-kappa Bbreast cancerNF-κB pathwaySNP-SNP interactionsurvival analysis
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