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

Hoffmann, Thomas J.; Passarelli, Michael N.; Graff, Rebecca E.; Emami, Nima C.; Sakoda, Lori C.; Jorgenson, Eric; Habel, Laurel A; Shan, Jun; Ranatunga, Dilrini K. and Quesenberry, Charles P., et al. (2017) In Nature Communications 8.
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... (More)

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.

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@article{4026667a-89cb-461a-96ce-78aec2ed24a9,
  abstract     = {<p>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&lt;5 × 10<sup>-8</sup>) 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.</p>},
  articleno    = {14248},
  author       = {Hoffmann, Thomas J. and Passarelli, Michael N. and Graff, Rebecca E. and Emami, Nima C. and Sakoda, Lori C. and Jorgenson, Eric and Habel, Laurel A and Shan, Jun and Ranatunga, Dilrini K. and Quesenberry, Charles P. and Chao, Chun R. and Ghai, Nirupa R. and Aaronson, David and Presti, Joseph and Nordström, Tobias and Wang, Zhaoming and Berndt, Sonja I and Chanock, Stephen J and Mosley, Jonathan D. and Klein, Robert J. and Middha, Mridu and Lilja, Hans and Melander, Olle and Kvale, Mark N. and Kwok, Pui Yan and Schaefer, Catherine and Risch, Neil and Van Den Eeden, Stephen K and Witte, John S.},
  issn         = {2041-1723},
  language     = {eng},
  month        = {01},
  publisher    = {Nature Publishing Group},
  series       = {Nature Communications},
  title        = {Genome-wide association study of prostate-specific antigen levels identifies novel loci independent of prostate cancer},
  url          = {http://dx.doi.org/10.1038/ncomms14248},
  volume       = {8},
  year         = {2017},
}