dc.contributor.author | FitzGerald, LM | |
dc.contributor.author | Zhao, S | |
dc.contributor.author | Leonardson, A | |
dc.contributor.author | Geybels, MS | |
dc.contributor.author | Kolb, S | |
dc.contributor.author | Lin, DW | |
dc.contributor.author | Wright, JL | |
dc.contributor.author | Eeles, R | |
dc.contributor.author | Kote-Jarai, Z | |
dc.contributor.author | Govindasami, K | |
dc.contributor.author | Giles, GG | |
dc.contributor.author | Southey, MC | |
dc.contributor.author | Schleutker, J | |
dc.contributor.author | Tammela, TL | |
dc.contributor.author | Sipeky, C | |
dc.contributor.author | Penney, KL | |
dc.contributor.author | Stampfer, MJ | |
dc.contributor.author | Gronberg, H | |
dc.contributor.author | Wiklund, F | |
dc.contributor.author | Stattin, P | |
dc.contributor.author | Hugosson, J | |
dc.contributor.author | Karyadi, DM | |
dc.contributor.author | Ostrander, EA | |
dc.contributor.author | Feng, Z | |
dc.contributor.author | Stanford, JL | |
dc.date.accessioned | 2018-01-17T15:19:45Z | |
dc.date.issued | 2018-06-01 | |
dc.identifier.citation | Prostate cancer and prostatic diseases, 2018, 21 (2), pp. 228 - 237 | |
dc.identifier.issn | 1365-7852 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/1000 | |
dc.identifier.eissn | 1476-5608 | |
dc.identifier.doi | 10.1038/s41391-017-0029-2 | |
dc.description.abstract | BACKGROUND: 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.format | Print-Electronic | |
dc.format.extent | 228 - 237 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PUBLISHING GROUP | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc/4.0 | |
dc.subject | Humans | |
dc.subject | Prostatic Neoplasms | |
dc.subject | DNA Repair Enzymes | |
dc.subject | DNA Modification Methylases | |
dc.subject | Tumor Suppressor Proteins | |
dc.subject | Interleukin-4 | |
dc.subject | Prognosis | |
dc.subject | Survival Rate | |
dc.subject | Cohort Studies | |
dc.subject | Follow-Up Studies | |
dc.subject | Germ-Line Mutation | |
dc.subject | Polymorphism, Single Nucleotide | |
dc.subject | Adult | |
dc.subject | Aged | |
dc.subject | Aged, 80 and over | |
dc.subject | Middle Aged | |
dc.subject | Male | |
dc.subject | Proto-Oncogene Proteins c-akt | |
dc.subject | Clinical Trials as Topic | |
dc.subject | Biomarkers, Tumor | |
dc.title | Germline variants in IL4, MGMT and AKT1 are associated with prostate cancer-specific mortality: An analysis of 12,082 prostate cancer cases. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2017-11-20 | |
rioxxterms.versionofrecord | 10.1038/s41391-017-0029-2 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by-nc-sa/4.0 | |
rioxxterms.licenseref.startdate | 2018-06 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Prostate cancer and prostatic diseases | |
pubs.issue | 2 | |
pubs.notes | Not 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-status | Published | |
pubs.volume | 21 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Oncogenetics | |
dc.contributor.icrauthor | Eeles, Rosalind | |
dc.contributor.icrauthor | Kote-Jarai, Zsofia | |