Genetic correction of PSA values using sequence variants associated with PSA levels

• Published in: Science Translational Medicine
• Main Authors: Gudmundsson, Julius, Besenbacher, Soren, Sulem, Patrick, Gudbjartsson, Daniel F, Olafsson, Isleifur, Arinbjarnarson, Sturla, Agnarsson, Bjarni A, Benediktsdottir, Kristrun R, Isaksson, Helgi J, Kostic, Jelena P, Gudjonsson, Sigurjon A, Stacey, Simon N, Gylfason, Arnaldur, Sigurdsson, Asgeir, Holm, Hilma, Bjornsdottir, Unnur S, Eyjolfsson, Gudmundur I, Navarrete, Sebastian, Fuertes, Fernando, Garcia-Prats, Maria D, Polo, Eduardo, Checherita, Ionel A, Jinga, Mariana, Badea, Paula, Aben, Katja K, Schalken, Jack A, van Oort, Inge M, Sweep, Fred C, Helfand, Brian T, Davis, Michael, Donovan, Jenny L, Hamdy, Freddie C, Kristjansson, Kristleifur, Gulcher, Jeffrey R, Masson, Gisli, Kong, Augustine, Catalona, William J, Mayordomo, Jose I, Geirsson, Gudmundur, Einarsson, Gudmundur V, Barkardottir, Rosa B, Jonsson, Eirikur, Jinga, Viorel, Mates, Dana, Kiemeney, Lambertus A, Neal, David E, Thorsteinsdottir, Unnur, Rafnar, Thorunn, Stefansson, Kari
• Other Authors: deCODE genetics, IS-101 Reykjavik, Iceland. [e-mail]
• Format: Article in Journal/Newspaper
• Language: English
• Published: American Association for the Advancement of Science 2011
• Subjects: Early Detection of Cancer; Genetic Markers; Humans; Kallikreins; Male; Polymorphism; Single Nucleotide; Prostate-Specific Antigen; Prostatic Neoplasms; Prostatic Secretory Proteins; Receptor; Fibroblast Growth Factor; Type 2; T-Box Domain Proteins; Telomerase; Tumor Markers; Biological; Iceland
• Online Access: http://hdl.handle.net/2336/128035; https://doi.org/10.1126/scitranslmed.3001513

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field Measuring serum levels of the prostate-specific antigen (PSA) is the most common screening method for prostate cancer. However, PSA levels are affected by a number of factors apart from neoplasia. Notably, around 40% of the variability of PSA levels in the general population is accounted for by inherited factors, suggesting that it may be possible to improve both sensitivity and specificity by adjusting test results for genetic effects. To search for sequence variants that associate with PSA levels, we performed a genome-wide association study and follow-up analysis using PSA information from 15,757 Icelandic and 454 British men not diagnosed with prostate cancer. Overall, we detected a genome-wide significant association between PSA levels and single-nucleotide polymorphisms (SNPs) at six loci: 5p15.33 (rs2736098), 10q11 (rs10993994), 10q26 (rs10788160), 12q24 (rs11067228), 17q12 (rs4430796), and 19q13.33 [rs17632542 (KLK3: I179T)], each with P(combined) <3 × 10(-10). Among 3834 men who underwent a biopsy of the prostate, the 10q26, 12q24, and 19q13.33 alleles that associate with high PSA levels are associated with higher probability of a negative biopsy (odds ratio between 1.15 and 1.27). Assessment of association between the six loci and prostate cancer risk in 5325 cases and 41,417 controls from Iceland, the Netherlands, Spain, Romania, and the United States showed that the SNPs at 10q26 and 12q24 were exclusively associated with PSA levels, whereas the other four loci also were associated with prostate cancer risk. We propose that a personalized PSA cutoff value, based on genotype, should be used when deciding to perform a prostate biopsy. info:eu-repo/grantAgreement/EC/FP7/202059/ 218071 Urological Research Foundation P50 CA90386-05S2 Robert H. Lurie Comprehensive Cancer Center p30 CA60553 Health Technology Assessment Programme 96/20/06 96/20/99 Department of Health, England Cancer Research ...