Fine Mapping the \(KLK3\) Locus on Chromosome 19q13.33 Associated With Prostate Cancer Susceptibility and PSA Levels

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Fine Mapping the \(KLK3\) Locus on Chromosome 19q13.33 Associated With Prostate Cancer Susceptibility and PSA Levels

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dc.contributor.author Parikh, Hemang
dc.contributor.author Wang, Zhaoming
dc.contributor.author Pettigrew, Kerry A.
dc.contributor.author Jia, Jinping
dc.contributor.author Daugherty, Sarah
dc.contributor.author Yeager, Meredith
dc.contributor.author Jacobs, Kevin B.
dc.contributor.author Hutchinson, Amy
dc.contributor.author Burdett, Laura
dc.contributor.author Cullen, Michael
dc.contributor.author Qi, Liqun
dc.contributor.author Boland, Joseph
dc.contributor.author Collins, Irene
dc.contributor.author Albert, Thomas J.
dc.contributor.author Hveem, Kristian
dc.contributor.author Cancel-Tassin, Geraldine
dc.contributor.author Cussenot, Olivier
dc.contributor.author Valeri, Antoine
dc.contributor.author Virtamo, Jarmo
dc.contributor.author Thun, Michael J.
dc.contributor.author Feigelson, Heather Spencer
dc.contributor.author Diver, W. Ryan
dc.contributor.author Chatterjee, Nilanjan
dc.contributor.author Thomas, Gilles
dc.contributor.author Albanes, Demetrius
dc.contributor.author Chanock, Stephen J.
dc.contributor.author Hoover, Robert
dc.contributor.author Hayes, Richard B.
dc.contributor.author Berndt, Sonja I.
dc.contributor.author Sampson, Joshua
dc.contributor.author Amundadottir, Laufey
dc.contributor.author Vatten, Lars Johan
dc.contributor.author Hunter, David J.
dc.contributor.author Njølstad, Inger
dc.date.accessioned 2011-12-06T04:54:39Z
dc.date.issued 2011
dc.identifier.citation Parikh, 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.issn 0340-6717 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:5360626
dc.description.abstract Measurements 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.iso en_US en_US
dc.publisher Springer-Verlag en_US
dc.relation.isversionof doi://10.1007/s00439-011-0953-5 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3092924/pdf/ en_US
dash.license LAA
dc.title Fine Mapping the \(KLK3\) Locus on Chromosome 19q13.33 Associated With Prostate Cancer Susceptibility and PSA Levels en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal Human Genetics en_US
dash.depositing.author Hunter, David J.
dc.date.available 2011-12-06T04:54:39Z
dash.affiliation.other HMS^Ophthalmology en_US

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