ArticlePLoS genetics2014
Fine-mapping the HOXB region detects common variants tagging a rare coding allele: evidence for synthetic association in prostate cancer.
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Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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21citing papers in PubMed, 1 pooled it
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants.Nature communications · 2018Pooled it
- Rare Coding Variants Associated with Breast Cancer.Advances in experimental medicine and biology · 2021Article
- Overcoming the challenges of imputation of rare variants in a Taiwanese cohort.Translational cancer research · 2020Article
- Post-GWAS in prostate cancer: from genetic association to biological contribution.Nature reviews. Cancer · 2019Review
- A Review of Prostate Cancer Genome-Wide Association Studies (GWAS).Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2018Review
- Whole exome sequencing: a state-of-the-art approach for defining (and exploring!) genetic landscapes in pediatric nephrology.Pediatric nephrology (Berlin, Germany) · 2018Review
- Improving imputation in disease-relevant regions: lessons from cystic fibrosis.NPJ genomic medicine · 2018Article
- Trans-ethnic follow-up of breast cancer GWAS hits using the preferential linkage disequilibrium approach.Oncotarget · 2016Article
- Deep targeted sequencing of 12 breast cancer susceptibility regions in 4611 women across four different ethnicities.Breast cancer research : BCR · 2016Article
- Anticancer effect of deoxypodophyllotoxin induces apoptosis of human prostate cancer cells.Oncology letters · 2016Article
- Recurrent HOXB13 mutations in the Dutch population do not associate with increased breast cancer risk.Scientific reports · 2016Article
- Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation.Nature communications · 2016Article
- Rare high-impact disease variants: properties and identifications.Genetics research · 2016Article
- Biomarkers for prostate cancer: present challenges and future opportunities.Future science OA · 2016Review
- Strategies for Imputing and Analyzing Rare Variants in Association Studies.Trends in genetics : TIG · 2015Review
- Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans.Human molecular genetics · 2015Article
- Imputation of the rare HOXB13 G84E mutation and cancer risk in a large population-based cohort.PLoS genetics · 2015Article
- Article
- Genetic Variants Underlying Risk of Intracranial Aneurysms: Insights from a GWAS in Portugal.PloS one · 2015Article
- Disease genetics: insights into missing heritability.Nature reviews. Genetics · 2014Article
Corrections and comments
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Authors and funding
70 authors at 20 institutions in 10 countries.
Edward J SaundersThe Institute of Cancer Research, Sutton, Surrey, United Kingdom.
Tokhir DadaevThe Institute of Cancer Research, Sutton, Surrey, United Kingdom.
Daniel A LeongamornlertThe Institute of Cancer Research, Sutton, Surrey, United Kingdom.
Sarah Jugurnauth-LittleThe Institute of Cancer Research, Sutton, Surrey, United Kingdom.
Malgorzata TymrakiewiczThe Institute of Cancer Research, Sutton, Surrey, United Kingdom.
Fredrik WiklundDepartment of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
Ali Amin Al OlamaCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Laboratory, Cambridge, United Kingdom.
Sara BenllochCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Laboratory, Cambridge, United Kingdom.
David E NealSurgical Oncology (Uro-Oncology: S4), University of Cambridge, Addenbrooke's Hospital, Cambridge and Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Cambridge, United Kingdom.
Freddie C HamdyNuffield Department of Surgical Sciences, University of Oxford, Oxford, and Faculty of Medical Science, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
Jenny L DonovanSchool of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
Graham G GilesCancer Epidemiology Centre, The Cancer Council Victoria, Carlton, Victoria, Australia and Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, The University of Melbourne, Melbourne, Victoria, Australia.
Gianluca SeveriCancer Epidemiology Centre, The Cancer Council Victoria, Carlton, Victoria, Australia and Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, The University of Melbourne, Melbourne, Victoria, Australia.
Henrik GronbergDepartment of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
Markus AlyDepartment of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
Christopher A HaimanDepartment of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California, United States of America.
Fredrick SchumacherDepartment of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California, United States of America.
Brian E HendersonDepartment of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California, United States of America.
Sara LindstromProgram in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America.
Peter KraftProgram in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America.
David J HunterProgram in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America.
Susan GapsturEpidemiology Research Program, American Cancer Society, Atlanta, Georgia, United States of America.
Stephen ChanockDivision of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland, United States of America.
Sonja I BerndtDivision of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland, United States of America.
Demetrius AlbanesNutritional Epidemiology Branch, National Cancer Institute, NIH, EPS-3044, Bethesda, Maryland, United States of America.
Gerald AndrioleDivision of Urologic Surgery, Washington University School of Medicine, St. Louis, Missouri, United States of America.
Johanna SchleutkerDepartment of Medic Biochemistry and Genetics, University of Turku, Turku and Institute of Biomedical Technology and BioMediTech, University of Tampere and FimLab Laboratories, Tampere, Finland.
Maren WeischerDepartment of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark.
Børge G NordestgaardDepartment of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark.
Federico CanzianGenomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Daniele CampaDivision of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Elio RiboliDepartment of Epidemiology & Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
Tim J KeyCancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
Ruth C TravisCancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
Sue A InglesDepartment of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California, United States of America.
Esther M JohnCancer Prevention Institute of California, Fremont, California, United States of America, and Stanford University School of Medicine, Stanford, California, United States of America.
Richard B HayesDivision of Epidemiology, Department of Population Health, NYU Langone Medical Center, NYU Cancer Institute, New York, New York, United States of America.
Paul PharoahCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Laboratory, Cambridge, United Kingdom.
Kay-Tee KhawClinical Gerontology Unit, University of Cambridge, Cambridge, United Kingdom.
Janet L StanfordDepartment of Epidemiology, School of Public Health, University of Washington and Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
Elaine A OstranderNational Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
Lisa B SignorelloInternational Epidemiology Institute, Rockville, Maryland, and Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
Stephen N ThibodeauMayo Clinic, Rochester, Minnesota, United States of America.
Daniel SchaidMayo Clinic, Rochester, Minnesota, United States of America.
Christiane MaierDepartment of Urology, University Hospital Ulm and Institute of Human Genetics University Hospital Ulm, Ulm, Germany.
Adam S KibelDivision of Urologic Surgery, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
Cezary CybulskiInternational Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
Lisa Cannon-AlbrightDivision of Genetic Epidemiology, Department of Medicine, University of Utah School of Medicine and George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, Utah, United States of America.
Hermann BrennerDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Jong Y ParkDepartment of Cancer Epidemiology, H. Lee Moffitt Cancer Center, Tampa, Florida, United States of America.
Radka KanevaMolecular Medicine Center and Department of Medical Chemistry and Biochemistry, Medical University - Sofia, Sofia, Bulgaria.
Jyotsna BatraAustralian Prostate Cancer Research Centre-Qld, Institute of Health and Biomedical Innovation and School of Biomedical Science, Queensland University of Technology, Brisbane, Queensland, Australia.
Judith A ClementsAustralian Prostate Cancer Research Centre-Qld, Institute of Health and Biomedical Innovation and School of Biomedical Science, Queensland University of Technology, Brisbane, Queensland, Australia.
Manuel R TeixeiraBiomedical Sciences Institute (ICBAS), Porto University, Porto, and Department of Genetics, Portuguese Oncology Institute, Porto, Portugal.
Jianfeng XuCenter for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States of America.
Christos MikropoulosThe Institute of Cancer Research, Sutton, Surrey, United Kingdom.
Chee GohThe Institute of Cancer Research, Sutton, Surrey, United Kingdom.
Koveela GovindasamiThe Institute of Cancer Research, Sutton, Surrey, United Kingdom.
Michelle GuyThe Institute of Cancer Research, Sutton, Surrey, United Kingdom.
Rosemary A WilkinsonThe Institute of Cancer Research, Sutton, Surrey, United Kingdom.
Emma J SawyerThe Institute of Cancer Research, Sutton, Surrey, United Kingdom.
Angela MorganThe Institute of Cancer Research, Sutton, Surrey, United Kingdom.
COGS-CRUK GWAS-ELLIPSE (Part of GAME-ON) Initiative
UK Genetic Prostate Cancer Study Collaborators
UK ProtecT Study Collaborators
PRACTICAL Consortium
Douglas F EastonCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Laboratory, Cambridge, United Kingdom.
Ken MuirWarwick Medical School, University of Warwick, Coventry, United Kingdom.
Rosalind A EelesThe Institute of Cancer Research, Sutton, Surrey, United Kingdom.
Zsofia Kote-JaraiThe Institute of Cancer Research, Sutton, Surrey, United Kingdom.
Institute of Cancer Research · GBUniversity of Cambridge · GBUniversity of Southern California · USGerman Cancer Research Center · DEHarvard University · USKarolinska Institutet · SENational Cancer Institute · USHerlev Hospital · DKMayo Clinic · USQueensland University of Technology · AUThe University of Melbourne · AUUniversity of Oxford · GBUniversity of Warwick · GBAmerican Cancer Society · USBrigham and Women's Hospital · USCancer Prevention Institute of California · USImperial College London · GBInstituto Português de Oncologia Francisco Gentil · PTInternational Hereditary Cancer Center · PLJohn Radcliffe Hospital · GB
Funding
Women's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI Felicity Enders · 1985 to 2026
$151.3MTRANSLATIONAL RESEARCHP30CA076292 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI KENNETH Lynn WRIGHT · 1998 to 2026
$93.5MFinding Genes for Human Prostate CancerZIAHG200325 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI OSTRANDER, ELAINE · 2009 to 2021
$17.7MCancer Research UK 10118Cancer Research UK 10119Cancer Research UK 10124Cancer Research UK 11022Cancer Research UK 14136Cancer Research UK 15007Cancer Research UK 16491Cancer Research UK 16561Cancer Research UK 16563Cancer Research UK 17528Cancer Research UK C5047/A15007Cancer Research UK C8197/A10123Cancer Research UK C8197/A10865Medical Research Council G0401527Medical Research Council G0900871Medical Research Council G1000143NCI NIH HHS P30 CA015083NCI NIH HHS P30 CA076292
Abstract
The HOXB13 gene has been implicated in prostate cancer (PrCa) susceptibility. We performed a high resolution fine-mapping analysis to comprehensively evaluate the association between common genetic variation across the HOXB genetic locus at 17q21 and PrCa risk. This involved genotyping 700 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of 3195 SNPs in 20,440 PrCa cases and 21,469 controls in The PRACTICAL consortium. We identified a cluster of highly correlated common variants situated within or closely upstream of HOXB13 that were significantly associated with PrCa risk, described by rs117576373 (OR 1.30, P = 2.62×10(-14)). Additional genotyping, conditional regression and haplotype analyses indicated that the newly identified common variants tag a rare, partially correlated coding variant in the HOXB13 gene (G84E, rs138213197), which has been identified recently as a moderate penetrance PrCa susceptibility allele. The potential for GWAS associations detected through common SNPs to be driven by rare causal variants with higher relative risks has long been proposed; however, to our knowledge this is the first experimental evidence for this phenomenon of synthetic association contributing to cancer susceptibility.
Indexed as
Genetic Predisposition to DiseaseGenetic VariationAllelesChromosomes, Human, Pair 17Genome-Wide Association StudyGenotypeHomeodomain ProteinsHumansMalePolymorphism, Single NucleotideProstatic NeoplasmsRisk FactorsHomeodomain ProteinsHOXB13 protein, human
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