Evidence map›Paper›PMID 26387087›Full record

ArticleCancer causes & control : CCC2015

The effects of height and BMI on prostate cancer incidence and mortality: a Mendelian randomization study in 20,848 cases and 20,214 controls from the PRACTICAL consortium.

Neil M Davies, Tom R Gaunt, Sarah J Lewis, Jeff Holly, Jenny L Donovan, Freddie C Hamdy, John P Kemp, Rosalind Eeles, Doug Easton, Zsofia Kote-Jarai and 30 more

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

Article in Cancer causes & control : CCC, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed, 7 pooled it
8.9field-weighted citation impact, top 2% 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

50 citing papers in PubMed, 7 syntheses or guidelines pooled it, 100 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

40 authors at 20 institutions in 12 countries.

Neil M DaviesSchool of Social and Community Medicine, University of Bristol, Bristol, UK. neil.davies@bristol.ac.uk.
Tom R GauntSchool of Social and Community Medicine, University of Bristol, Bristol, UK.
Sarah J LewisSchool of Social and Community Medicine, University of Bristol, Bristol, UK.
Jeff HollySchool of Clinical Sciences, University of Bristol, Bristol, BS10 5NB, UK.
Jenny L DonovanSchool of Social and Community Medicine, University of Bristol, Bristol, UK.
Freddie C HamdyNuffield Department of Surgery, University of Oxford, Oxford, UK.
John P KempMRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Rosalind EelesThe Institute of Cancer Research, London, SM2 5NG, UK.
Doug EastonStrangeways Laboratory, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Worts Causeway, Cambridge, UK.
Zsofia Kote-JaraiThe Institute of Cancer Research, London, SM2 5NG, UK.
Ali Amin Al OlamaStrangeways Laboratory, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Worts Causeway, Cambridge, UK.
Sara BenllochStrangeways Laboratory, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Worts Causeway, Cambridge, UK.
Kenneth MuirInstitute of Population Health, University of Manchester, Manchester, UK.
Graham G GilesCancer Epidemiology Centre, The Cancer Council Victoria, 615 St Kilda Road, Melbourne, VIC, Australia.
Fredrik WiklundDepartment of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
Henrik GronbergDepartment 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, CA, USA.
Johanna SchleutkerDepartment of Medical Biochemistry and Genetics, University of Turku, Turku, Finland.
Børge G NordestgaardDepartment of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, 2730, Herlev, Denmark.
Ruth C TravisCancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
David NealSurgical Oncology (Uro-Oncology: S4), University of Cambridge, Addenbrooke's Hospital, Hills Road, Box 279, Cambridge, UK.
Nora PashayanStrangeways Laboratory, Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Worts Causeway, Cambridge, UK.
Kay-Tee KhawCambridge Institute of Public Health, University of Cambridge, Forvie Site, Robinson Way, Cambridge, CB2 0SR, UK.
Janet L StanfordDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
William J BlotInternational Epidemiology Institute, 1455 Research Blvd., Suite 550, Rockville, MD, 20850, USA.
Stephen ThibodeauMayo Clinic, Rochester, MN, USA.
Christiane MaierDepartment of Urology, University Hospital Ulm, Ulm, Germany.
Adam S KibelBrigham and Women's Hospital/Dana-Farber Cancer Institute, 45 Francis Street-ASB II-3, Boston, MA, 02115, USA.
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, Salt Lake City, UT, USA.
Hermann BrennerDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Jong ParkDivision of Cancer Prevention and Control, H. Lee Moffitt Cancer Center, 12902 Magnolia Dr., Tampa, FL, USA.
Radka KanevaMolecular Medicine Center and Department of Medical Chemistry and Biochemistry, Medical University Sofia, 2 Zdrave St, 1431, Sofia, Bulgaria.
Jyotsna BatraAustralian Prostate Cancer Research Centre-Qld, Institute of Health and Biomedical Innovation and School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, Australia.
Manuel R TeixeiraDepartment of Genetics, Portuguese Oncology Institute, Porto, Portugal.
Hardev PandhaThe University of Surrey, Guildford, Surrey, GU2 7XH, UK.
PRACTICAL consortium
Mark LathropCommissariat à l'Energie Atomique, Center National de Génotypage, Evry, France.
George Davey SmithSchool of Social and Community Medicine, University of Bristol, Bristol, UK.
Richard M MartinSchool of Social and Community Medicine, University of Bristol, Bristol, UK. richard.martin@bristol.ac.uk.
University of Bristol · GBUniversity of Cambridge · GBInstitute of Cancer Research · GBKarolinska Institutet · SEUniversity of Oxford · GBAddenbrooke's Hospital · GBBrigham and Women's Hospital · USFimlab (Finland) · FIFred Hutch Cancer Center · USGerman Cancer Research Center · DEHerlev Hospital · DKInstituto Português de Oncologia Francisco Gentil · PTInternational Epidemiology Institute · USInternational Hereditary Cancer Center · PLMayo Clinic in Arizona · USMcGill University and Génome Québec Innovation Centre · CAMedical University of Sofia · BGMoffitt Cancer Center · USMRC Epidemiology Unit · GBNational Institute for Health Research · GB

Funding

Women's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI Keith L. Knutson · 1985 to 2026
$151.3M
Southern Community Cohort StudyR01CA092447 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BLOT, WILLIAM J., ZHENG, WEI · 2001 to 2015
$74.0M
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
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
Cancer Research UK 13065Cancer Research UK 14136Cancer Research UK 15007Cancer Research UK 16491Cancer Research UK 16563Cancer Research UK 17528Cancer Research UK 19170Cancer Research UK A19169Cancer Research UK C12292/A11174Cancer Research UK C1281/A12014Cancer Research UK C1287/A10118Cancer Research UK C1287/A 10710Cancer Research UK C16913/A6135Cancer Research UK C18281/A19169Cancer Research UK C5047/A10692Cancer Research UK C5047/A15007Cancer Research UK C5047/A3354Cancer Research UK C5047/A7357Cancer Research UK C5047/A8384CIHRDepartment of HealthMedical Research Council G0401527Medical Research Council G0500966Medical Research Council G0500966/75466Medical Research Council G0600705Medical Research Council G1000143Medical Research Council MC_UU_12013/1Medical Research Council MC_UU_12013/8Medical Research Council MC_UU_12013/9NCI NIH HHS 1U19 CA148065NCI NIH HHS 1U19 CA148112NCI NIH HHS 1U19 CA148537NCI NIH HHS 1 U19 CA 148537-01NCI NIH HHS CA128978NCI NIH HHS P30 CA015083NCI NIH HHS R01 CA092447NCI NIH HHS R01 CA128978NCI NIH HHS U19 CA148065NCI NIH HHS U19 CA148112NCI NIH HHS U19 CA148537
6 · The paper itself

Abstract

backgroundEpidemiological studies suggest a potential role for obesity and determinants of adult stature in prostate cancer risk and mortality, but the relationships described in the literature are complex. To address uncertainty over the causal nature of previous observational findings, we investigated associations of height- and adiposity-related genetic variants with prostate cancer risk and mortality.

methodsWe conducted a case-control study based on 20,848 prostate cancers and 20,214 controls of European ancestry from 22 studies in the PRACTICAL consortium. We constructed genetic risk scores that summed each man's number of height and BMI increasing alleles across multiple single nucleotide polymorphisms robustly associated with each phenotype from published genome-wide association studies.

resultsThe genetic risk scores explained 6.31 and 1.46% of the variability in height and BMI, respectively. There was only weak evidence that genetic variants previously associated with increased BMI were associated with a lower prostate cancer risk (odds ratio per standard deviation increase in BMI genetic score 0.98; 95% CI 0.96, 1.00; p = 0.07). Genetic variants associated with increased height were not associated with prostate cancer incidence (OR 0.99; 95% CI 0.97, 1.01; p = 0.23), but were associated with an increase (OR 1.13; 95 % CI 1.08, 1.20) in prostate cancer mortality among low-grade disease (p heterogeneity, low vs. high grade <0.001). Genetic variants associated with increased BMI were associated with an increase (OR 1.08; 95 % CI 1.03, 1.14) in all-cause mortality among men with low-grade disease (p heterogeneity = 0.03).

conclusionsWe found little evidence of a substantial effect of genetically elevated height or BMI on prostate cancer risk, suggesting that previously reported observational associations may reflect common environmental determinants of height or BMI and prostate cancer risk. Genetically elevated height and BMI were associated with increased mortality (prostate cancer-specific and all-cause, respectively) in men with low-grade disease, a potentially informative but novel finding that requires replication.

Indexed as

Body Mass IndexPhenotypeAdiposityAgedAllelesBody HeightCase-Control StudiesGenetic VariationGenotypeHumansIncidenceMaleMendelian Randomization AnalysisMiddle AgedObesityPolymorphism, Single NucleotideBody mass indexHeightInstrumental variables analysisMendelian randomizationProstate cancerSingle nucleotide polymorphisms

Identifiers

PMID26387087
PMCPMC4596899
OpenAlexW2154037729

What OpenQuestion holds

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LicenceCC BY
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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.