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dc.contributor.authorFitzGerald, LM
dc.contributor.authorZhao, S
dc.contributor.authorLeonardson, A
dc.contributor.authorGeybels, MS
dc.contributor.authorKolb, S
dc.contributor.authorLin, DW
dc.contributor.authorWright, JL
dc.contributor.authorEeles, R
dc.contributor.authorKote-Jarai, Z
dc.contributor.authorGovindasami, K
dc.contributor.authorGiles, GG
dc.contributor.authorSouthey, MC
dc.contributor.authorSchleutker, J
dc.contributor.authorTammela, TL
dc.contributor.authorSipeky, C
dc.contributor.authorPenney, KL
dc.contributor.authorStampfer, MJ
dc.contributor.authorGronberg, H
dc.contributor.authorWiklund, F
dc.contributor.authorStattin, P
dc.contributor.authorHugosson, J
dc.contributor.authorKaryadi, DM
dc.contributor.authorOstrander, EA
dc.contributor.authorFeng, Z
dc.contributor.authorStanford, JL
dc.date.accessioned2018-01-17T15:19:45Z
dc.date.issued2018-06
dc.identifier.citationProstate cancer and prostatic diseases, 2018, 21 (2), pp. 228 - 237
dc.identifier.issn1365-7852
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1000
dc.identifier.eissn1476-5608
dc.identifier.doi10.1038/s41391-017-0029-2
dc.description.abstractBACKGROUND:Prostate cancer (PCa) is a leading cause of mortality and genetic factors can influence tumour aggressiveness. Several germline variants have been associated with PCa-specific mortality (PCSM), but further replication evidence is needed. METHODS:Twenty-two previously identified PCSM-associated genetic variants were genotyped in seven PCa cohorts (12,082 patients; 1544 PCa deaths). For each cohort, Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals for risk of PCSM associated with each variant. Data were then combined using a meta-analysis approach. RESULTS:Fifteen SNPs were associated with PCSM in at least one of the seven cohorts. In the meta-analysis, after adjustment for clinicopathological factors, variants in the MGMT (rs2308327; HR 0.90; p-value = 3.5 × 10-2) and IL4 (rs2070874; HR 1.22; p-value = 1.1 × 10-3) genes were confirmed to be associated with risk of PCSM. In analyses limited to men diagnosed with local or regional stage disease, a variant in AKT1, rs2494750, was also confirmed to be associated with PCSM risk (HR 0.81; p-value = 3.6 × 10-2). CONCLUSIONS:This meta-analysis confirms the association of three genetic variants with risk of PCSM, providing further evidence that genetic background plays a role in PCa-specific survival. While these variants alone are not sufficient as prognostic biomarkers, these results may provide insights into the biological pathways modulating tumour aggressiveness.
dc.formatPrint-Electronic
dc.format.extent228 - 237
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0
dc.subjectHumans
dc.subjectProstatic Neoplasms
dc.subjectDNA Repair Enzymes
dc.subjectDNA Modification Methylases
dc.subjectTumor Suppressor Proteins
dc.subjectInterleukin-4
dc.subjectPrognosis
dc.subjectSurvival Rate
dc.subjectCohort Studies
dc.subjectFollow-Up Studies
dc.subjectGerm-Line Mutation
dc.subjectPolymorphism, Single Nucleotide
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectMiddle Aged
dc.subjectMale
dc.subjectProto-Oncogene Proteins c-akt
dc.subjectClinical Trials as Topic
dc.subjectBiomarkers, Tumor
dc.titleGermline variants in IL4, MGMT and AKT1 are associated with prostate cancer-specific mortality: An analysis of 12,082 prostate cancer cases.
dc.typeJournal Article
dcterms.dateAccepted2017-11-20
rioxxterms.versionofrecord10.1038/s41391-017-0029-2
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc-sa/4.0
rioxxterms.licenseref.startdate2018-06
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfProstate cancer and prostatic diseases
pubs.issue2
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Oncogenetics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Oncogenetics
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Oncogenetics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Oncogenetics
pubs.publication-statusPublished
pubs.volume21
pubs.embargo.termsNot known
icr.researchteamOncogeneticsen_US
dc.contributor.icrauthorEeles, Rosalinden
dc.contributor.icrauthorKote-Jarai, Zsofiaen


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