Genome-wide association study of prostate-specific antigen levels identifies novel loci independent of prostate cancer View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-01-31

AUTHORS

Thomas J Hoffmann, Michael N Passarelli, Rebecca E Graff, Nima C Emami, Lori C Sakoda, Eric Jorgenson, Laurel A Habel, Jun Shan, Dilrini K Ranatunga, Charles P Quesenberry, Chun R Chao, Nirupa R Ghai, David Aaronson, Joseph Presti, Tobias Nordström, Zhaoming Wang, Sonja I Berndt, Stephen J Chanock, Jonathan D Mosley, Robert J Klein, Mridu Middha, Hans Lilja, Olle Melander, Mark N Kvale, Pui-Yan Kwok, Catherine Schaefer, Neil Risch, Stephen K Van Den Eeden, John S Witte

ABSTRACT

Prostate-specific antigen (PSA) levels have been used for detection and surveillance of prostate cancer (PCa). However, factors other than PCa-such as genetics-can impact PSA. Here we present findings from a genome-wide association study (GWAS) of PSA in 28,503 Kaiser Permanente whites and 17,428 men from replication cohorts. We detect 40 genome-wide significant (P<5 × 10-8) single-nucleotide polymorphisms (SNPs): 19 novel, 15 previously identified for PSA (14 of which were also PCa-associated), and 6 previously identified for PCa only. Further analysis incorporating PCa cases suggests that at least half of the 40 SNPs are PSA-associated independent of PCa. The 40 SNPs explain 9.5% of PSA variation in non-Hispanic whites, and the remaining GWAS SNPs explain an additional 31.7%; this percentage is higher in younger men, supporting the genetic basis of PSA levels. These findings provide important information about genetic markers for PSA that may improve PCa screening, thereby reducing over-diagnosis and over-treatment. More... »

PAGES

14248

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ncomms14248

    DOI

    http://dx.doi.org/10.1038/ncomms14248

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1083396291

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/28139693


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