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dc.contributor.authorParikh, Hemang
dc.contributor.authorWang, Zhaoming
dc.contributor.authorPettigrew, Kerry A.
dc.contributor.authorJia, Jinping
dc.contributor.authorDaugherty, Sarah
dc.contributor.authorYeager, Meredith
dc.contributor.authorJacobs, Kevin B.
dc.contributor.authorHutchinson, Amy
dc.contributor.authorBurdett, Laura
dc.contributor.authorCullen, Michael
dc.contributor.authorQi, Liqun
dc.contributor.authorBoland, Joseph
dc.contributor.authorCollins, Irene
dc.contributor.authorAlbert, Thomas J.
dc.contributor.authorHveem, Kristian
dc.contributor.authorCancel-Tassin, Geraldine
dc.contributor.authorCussenot, Olivier
dc.contributor.authorValeri, Antoine
dc.contributor.authorVirtamo, Jarmo
dc.contributor.authorThun, Michael J.
dc.contributor.authorFeigelson, Heather Spencer
dc.contributor.authorDiver, W. Ryan
dc.contributor.authorChatterjee, Nilanjan
dc.contributor.authorThomas, Gilles
dc.contributor.authorAlbanes, Demetrius
dc.contributor.authorChanock, Stephen J.
dc.contributor.authorHoover, Robert
dc.contributor.authorHayes, Richard B.
dc.contributor.authorBerndt, Sonja I.
dc.contributor.authorSampson, Joshua
dc.contributor.authorAmundadottir, Laufey
dc.contributor.authorVatten, Lars Johan
dc.contributor.authorHunter, David J.
dc.contributor.authorNjølstad, Inger
dc.date.accessioned2011-12-06T04:54:39Z
dc.date.issued2011
dc.identifier.citationParikh, Hemang, Zhaoming Wang, Kerry A. Pettigrew, Jinping Jia, Sarah Daugherty, Meredith Yeager, Kevin B. Jacobs, and et al. 2011. Fine mapping the \(KLK3\) locus on chromosome 19q13.33 associated with prostate cancer susceptibility and PSA levels. Human Genetics 129(6): 675-685.en_US
dc.identifier.issn0340-6717en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:5360626
dc.description.abstractMeasurements of serum prostate-specific antigen (PSA) protein levels form the basis for a widely used test to screen men for prostate cancer. Germline variants in the gene that encodes the PSA protein (\(KLK3\)) have been shown to be associated with both serum PSA levels and prostate cancer. Based on a resequencing analysis of a 56 kb region on chromosome 19q13.33, centered on the \(KLK3\) gene, we fine mapped this locus by genotyping tag SNPs in 3,522 prostate cancer cases and 3,338 controls from five case–control studies. We did not observe a strong association with the \(KLK3\) variant, reported in previous studies to confer risk for prostate cancer (rs2735839; P = 0.20) but did observe three highly correlated SNPs (rs17632542, rs62113212 and rs62113214) associated with prostate cancer [P = 3.41 x 10\(^{-4}\), per-allele trend odds ratio (OR) = 0.77, 95% CI = 0.67–0.89]. The signal was apparent only for nonaggressive prostate cancer cases with Gleason score < 7 and disease stage < III (P = 4.72 x 10\(^{-5}\), per-allele trend OR = 0.68, 95% CI = 0.57–0.82) and not for advanced cases with Gleason score \(\geq\) 8 or stage \(\geq\) III (P = 0.31, per-allele trend OR = 1.12, 95% CI = 0.90–1.40). One of the three highly correlated SNPs,rs17632542, introduces a non-synonymous amino acid change in the \(KLK3\) protein with a predicted benign or neutral functional impact. Baseline PSA levels were 43.7% higher in control subjects with no minor alleles (1.61 ng/ml, 95% CI = 1.49–1.72) than in those with one or more minor alleles at any one of the three SNPs (1.12 ng/ml, 95% CI = 0.96–1.28) (P = 9.70 x 10\(^{-5}\)). Together our results suggest that germline \(KLK3\) variants could influence the diagnosis of nonaggressive prostate cancer by influencing the likelihood of biopsy.en_US
dc.language.isoen_USen_US
dc.publisherSpringer-Verlagen_US
dc.relation.isversionofdoi://10.1007/s00439-011-0953-5en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3092924/pdf/en_US
dash.licenseLAA
dc.titleFine Mapping the \(KLK3\) Locus on Chromosome 19q13.33 Associated With Prostate Cancer Susceptibility and PSA Levelsen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalHuman Geneticsen_US
dash.depositing.authorHunter, David J.
dc.date.available2011-12-06T04:54:39Z
dash.affiliation.otherHMS^Ophthalmologyen_US
dc.identifier.doi10.1007/s00439-011-0953-5*
dash.authorsorderedfalse
dash.contributor.affiliatedVatten, Lars Johan
dash.contributor.affiliatedHunter, David


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