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dc.contributor.authorSaunders, Edward Jen
dc.contributor.authorDadaev, Tokhiren
dc.contributor.authorLeongamornlert, Daniel Aen
dc.contributor.authorAmin Al Olama, Alien
dc.contributor.authorBenlloch, Saraen
dc.contributor.authorGiles, Graham Gen
dc.contributor.authorWiklund, Fredriken
dc.contributor.authorGrönberg, Henriken
dc.contributor.authorHaiman, Christopher Aen
dc.contributor.authorSchleutker, Johannaen
dc.contributor.authorNordestgaard, Børge Gen
dc.contributor.authorTravis, Ruth Cen
dc.contributor.authorNeal, Daviden
dc.contributor.authorPasayan, Noraen
dc.contributor.authorKhaw, Kay-Teeen
dc.contributor.authorStanford, Janet Len
dc.contributor.authorBlot, William Jen
dc.contributor.authorThibodeau, Stephen Nen
dc.contributor.authorMaier, Christianeen
dc.contributor.authorKibel, Adam Sen
dc.contributor.authorCybulski, Cezaryen
dc.contributor.authorCannon-Albright, Lisaen
dc.contributor.authorBrenner, Hermannen
dc.contributor.authorPark, Jong Yen
dc.contributor.authorKaneva, Radkaen
dc.contributor.authorBatra, Jyotsnaen
dc.contributor.authorTeixeira, Manuel Ren
dc.contributor.authorPandha, Hardeven
dc.contributor.authorGovindasami, Koveelaen
dc.contributor.authorMuir, Kenen
dc.contributor.authorThe, UK Genetic Prostate Cancer Study Collaboratorsen
dc.contributor.authorThe, UK ProtecT Study Collaboratorsen
dc.contributor.authorThe, PRACTICAL Consortiumen
dc.contributor.authorEaston, Douglasen
dc.contributor.authorEeles, Rosalind Aen
dc.contributor.authorKote-Jarai, Zsofiaen
dc.identifier.citationSuanders et al. British Journal of Cancer (2016) Vol. 114, pp. 945-952. doi: 10.1038/bjc.2016.50en
dc.description.abstractBackground: Germline mutations within DNA-repair genes are implicated in susceptibility to multiple forms of cancer. For prostate cancer (PrCa), rare mutations in BRCA2 and BRCA1 give rise to moderately elevated risk, whereas two of ~100 common, low-penetrance PrCa susceptibility variants identified so far by genome-wide association studies implicate RAD51B and RAD23B. Methods: Genotype data from the iCOGS array were imputed to the 1000 genomes phase 3 reference panel for 21 780 PrCa cases and 21 727 controls from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. We subsequently performed single variant, gene and pathway-level analyses using 81 303 SNPs within 20 Kb of a panel of 179 DNA-repair genes. Results: Single SNP analyses identified only the previously reported association with RAD51B. Gene-level analyses using the SKAT-C test from the SNP-set (Sequence) Kernel Association Test (SKAT) identified a significant association with PrCa for MSH5. Pathway-level analyses suggested a possible role for the translesion synthesis pathway in PrCa risk and Homologous recombination/Fanconi Anaemia pathway for PrCa aggressiveness, even though after adjustment for multiple testing these did not remain significant. Conclusions: MSH5 is a novel candidate gene warranting additional follow-up as a prospective PrCa-risk locus. MSH5 has previously been reported as a pleiotropic susceptibility locus for lung, colorectal and serous ovarian cancers.
dc.publisherNature Publishing Group
dc.rightsAttribution 2.0 UK: England & Wales*
dc.subjectDNA repairen
dc.subjectprostate canceren
dc.subjectgenome-wide association studyen
dc.titleGene and pathway level analyses of germline DNA-repair gene variants and prostate cancer susceptibility using the iCOGS-genotyping arrayen
dc.description.versionThis is the final version of the article. It first appeared from Nature Publishing Group via
prism.publicationNameBritish Journal of Canceren
dc.contributor.orcidAmin Al Olama, Ali [0000-0002-7178-3431]
dc.contributor.orcidKhaw, Kay-Tee [0000-0002-8802-2903]
dc.contributor.orcidEaston, Douglas [0000-0003-2444-3247]
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (G0500966)
pubs.funder-project-idNational Cancer Institute (NCI) (R01CA128978)
pubs.funder-project-idNational Cancer Institute (NCI) (U19CA148537)
pubs.funder-project-idMEDICAL RESEARCH COUNCIL (MR/N003284/1)
pubs.funder-project-idMRC (G0401527)
pubs.funder-project-idMRC (G1000143)
pubs.funder-project-idCancer Research UK (CRUK-A12014)
pubs.funder-project-idCancer Research UK (CRUK-A10118)
pubs.funder-project-idCancer Research UK (A8649)
cam.orpheus.successThu Jan 30 12:54:16 GMT 2020 - The item has an open VoR version.*

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Attribution 2.0 UK: England & Wales
Except where otherwise noted, this item's licence is described as Attribution 2.0 UK: England & Wales