Show simple item record

dc.contributor.authorAmin Al Olama, Ali
dc.contributor.authorBenlloch Garcia, Sara
dc.contributor.authorAntoniou, Antonis
dc.contributor.authorGiles, Graham G
dc.contributor.authorSeveri, Gianluca
dc.contributor.authorNeal, David E
dc.contributor.authorHamdy, Freddie C
dc.contributor.authorDonovan, Jenny L
dc.contributor.authorMuir, Kenneth
dc.contributor.authorSchleutker, Johanna
dc.contributor.authorHenderson, Brian E
dc.contributor.authorHaiman, Christopher A
dc.contributor.authorSchumacher, Fredrick R
dc.contributor.authorPashayan, Nora
dc.contributor.authorPharoah, Paul
dc.contributor.authorOstrander, Elaine A
dc.contributor.authorStanford, Janet L
dc.contributor.authorBatra, Jyotsna
dc.contributor.authorClements, Judith A
dc.contributor.authorChambers, Suzanne K
dc.contributor.authorWeischer, Maren
dc.contributor.authorNordestgaard, Børge G
dc.contributor.authorIngles, Sue A
dc.contributor.authorSorensen, Karina D
dc.contributor.authorOrntoft, Torben F
dc.contributor.authorPark, Jong Y
dc.contributor.authorCybulski, Cezary
dc.contributor.authorMaier, Christiane
dc.contributor.authorDoerk, Thilo
dc.contributor.authorDickinson, Joanne L
dc.contributor.authorCannon-Albright, Lisa
dc.contributor.authorBrenner, Hermann
dc.contributor.authorRebbeck, Timothy R
dc.contributor.authorZeigler-Johnson, Charnita
dc.contributor.authorHabuchi, Tomonori
dc.contributor.authorThibodeau, Stephen N
dc.contributor.authorCooney, Kathleen A
dc.contributor.authorChappuis, Pierre O
dc.contributor.authorHutter, Pierre
dc.contributor.authorKaneva, Radka P
dc.contributor.authorFoulkes, William D
dc.contributor.authorZeegers, Maurice P
dc.contributor.authorLu, Yong-Jie
dc.contributor.authorZhang, Hong-Wei
dc.contributor.authorStephenson, Robert
dc.contributor.authorCox, Angela
dc.contributor.authorSouthey, Melissa C
dc.contributor.authorSpurdle, Amanda B
dc.contributor.authorFitzGerald, Liesel
dc.contributor.authorLeongamornlert, Daniel
dc.contributor.authorSaunders, Edward
dc.contributor.authorTymrakiewicz, Malgorzata
dc.contributor.authorGuy, Michelle
dc.contributor.authorDadaev, Tokhir
dc.contributor.authorLittle, Sarah J
dc.contributor.authorGovindasami, Koveela
dc.contributor.authorSawyer, Emma
dc.contributor.authorWilkinson, Rosemary
dc.contributor.authorHerkommer, Kathleen
dc.contributor.authorHopper, John L
dc.contributor.authorLophatonanon, Aritaya
dc.contributor.authorRinckleb, Antje E
dc.contributor.authorKote-Jarai, Zsofia
dc.contributor.authorEeles, Rosalind A
dc.contributor.authorEaston, Douglas
dc.contributor.authorUK Genetic Prostate Cancer Study Collaborators/British Association of Urological Surgeons' Section of Oncology
dc.contributor.authorUK ProtecT Study Collaborators
dc.contributor.authorPRACTICAL Consortium
dc.date.accessioned2015-05-26T14:47:01Z
dc.date.available2015-05-26T14:47:01Z
dc.date.issued2015-07
dc.identifier.citationCancer Epidemiology, Biomarkers & Prevention, 24, 1124. 2015; doi: 10.1158/1055-9965.EPI-14-0317
dc.identifier.issn1055-9965
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/247997
dc.description.abstractBACKGROUND: Genome-wide association studies have identified multiple genetic variants associated with prostate cancer risk which explain a substantial proportion of familial relative risk. These variants can be used to stratify individuals by their risk of prostate cancer. METHODS: We genotyped 25 prostate cancer susceptibility loci in 40,414 individuals and derived a polygenic risk score (PRS). We estimated empirical odds ratios (OR) for prostate cancer associated with different risk strata defined by PRS and derived age-specific absolute risks of developing prostate cancer by PRS stratum and family history. RESULTS: The prostate cancer risk for men in the top 1% of the PRS distribution was 30.6 (95% CI, 16.4-57.3) fold compared with men in the bottom 1%, and 4.2 (95% CI, 3.2-5.5) fold compared with the median risk. The absolute risk of prostate cancer by age of 85 years was 65.8% for a man with family history in the top 1% of the PRS distribution, compared with 3.7% for a man in the bottom 1%. The PRS was only weakly correlated with serum PSA level (correlation = 0.09). CONCLUSIONS: Risk profiling can identify men at substantially increased or reduced risk of prostate cancer. The effect size, measured by OR per unit PRS, was higher in men at younger ages and in men with family history of prostate cancer. Incorporating additional newly identified loci into a PRS should improve the predictive value of risk profiles. IMPACT: We demonstrate that the risk profiling based on SNPs can identify men at substantially increased or reduced risk that could have useful implications for targeted prevention and screening programs.
dc.description.sponsorshipD F. Easton was recipient of the CR-UK grant C1287/A10118. R A. Eeles was recipient of the CR-UK grant C5047/A10692 and B E. Henderson was recipient of the NIH grant 1U19CA148537-01
dc.languageEnglish
dc.language.isoen
dc.publisherAmerican Association for Cancer Research (AACR)
dc.subjectProstate Cancer risk
dc.subjectGenitourinary Cancers: Prostate
dc.subjectRisk Assessment
dc.subjectMethodology
dc.subjectModelling and biostatistics
dc.subjectMethodology for SNP data analysis
dc.subjectStatistical methods in Genetics
dc.subjectGenetic and Molecular Epidemiology
dc.titleRisk Analysis of Prostate Cancer in PRACTICAL, a Multinational Consortium, Using 25 Known Prostate Cancer Susceptibility Loci.
dc.typeArticle
dc.description.versionThis is the author accepted manuscript. The final version is available via AACR at http://cebp.aacrjournals.org/content/early/2015/04/02/1055-9965.EPI-14-0317.long.
prism.publicationDate2015
prism.publicationNameCancer Epidemiol Biomarkers Prev
prism.volumeCancer Epidemiology, Biomarkers and Prevention
dc.rioxxterms.funderCRUK
dc.rioxxterms.funderNIH
dc.rioxxterms.projectidC1287/A10118
dc.rioxxterms.projectidC5047/A10692
dc.rioxxterms.projectid1U19CA148537-01
dcterms.dateAccepted2015-03-09
rioxxterms.versionofrecord10.1158/1055-9965.EPI-14-0317
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2015-04-02
dc.contributor.orcidAmin Al Olama, Ali [0000-0002-7178-3431]
dc.contributor.orcidAntoniou, Antonis [0000-0001-9223-3116]
dc.contributor.orcidPharoah, Paul [0000-0001-8494-732X]
dc.contributor.orcidEaston, Douglas [0000-0003-2444-3247]
dc.identifier.eissn1538-7755
rioxxterms.typeJournal Article/Review
pubs.funder-project-idNational Cancer Institute (U19CA148537)
pubs.funder-project-idCancer Research Uk (None)
pubs.funder-project-idCancer Research Uk (None)
pubs.funder-project-idCancer Research Uk (None)
pubs.funder-project-idCancer Research UK (CRUK-A10118)
cam.issuedOnline2015-04-02
rioxxterms.freetoread.startdate2016-04-02


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record