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

Show simple item record Parikh, Hemang Wang, Zhaoming Pettigrew, Kerry A. Jia, Jinping Daugherty, Sarah Yeager, Meredith Jacobs, Kevin B. Hutchinson, Amy Burdett, Laura Cullen, Michael Qi, Liqun Boland, Joseph Collins, Irene Albert, Thomas J. Hveem, Kristian Cancel-Tassin, Geraldine Cussenot, Olivier Valeri, Antoine Virtamo, Jarmo Thun, Michael J. Feigelson, Heather Spencer Diver, W. Ryan Chatterjee, Nilanjan Thomas, Gilles Albanes, Demetrius Chanock, Stephen J. Hoover, Robert Hayes, Richard B. Berndt, Sonja I. Sampson, Joshua Amundadottir, Laufey Vatten, Lars Johan Hunter, David J. Njølstad, Inger 2011-12-06T04:54:39Z 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.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 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 Hunter, David J. 2011-12-06T04:54:39Z
dash.affiliation.other HMS^Ophthalmology en_US

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