An analysis of the association between prostate cancer risk loci, PSA levels, disease aggressiveness and disease-specific mortality Journal Article


Authors: Sullivan, J.; Kopp, R.; Stratton, K.; Manschreck, C.; Corines, M.; Rau-Murthy, R.; Hayes, J.; Lincoln, A.; Ashraf, A.; Thomas, T.; Schrader, K.; Gallagher, D.; Hamilton, R.; Scher, H.; Lilja, H.; Scardino, P.; Eastham, J.; Offit, K.; Vijai, J.; Klein, R. J.
Article Title: An analysis of the association between prostate cancer risk loci, PSA levels, disease aggressiveness and disease-specific mortality
Abstract: BACKGROUND: Genome-wide association studies have identified multiple single-nucleotide polymorphsims (SNPs) associated with prostate cancer (PCa). Although these SNPs have been clearly associated with disease risk, their relationship with clinical outcomes is less clear. Our aim was to assess the frequency of known PCa susceptibility alleles within a single institution ascertainment and to correlate risk alleles with disease-specific outcomes. METHODS: We genotyped 1354 individuals treated for localised PCa between June 1988 and December 2007. Blood samples were prospectively collected and de-identified before being genotyped and matched to phenotypic data. We investigated associations between 61 SNPs and disease-specific end points using multivariable analysis and also determined if SNPs were associated with PSA at diagnosis. RESULTS: Seven SNPs showed associations on multivariable analysis (P<0.05), rs13385191 with both biochemical recurrence (BR) and castrate metastasis (CM), rs339331 (BR), rs1894292, rs17178655 and rs11067228 (CM), and rs11902236 and rs4857841 PCa-specific mortality. After applying a Bonferroni correction for number of SNPs (P<0.0008), the only persistent significant association was between rs17632542 (KLK3) and PSA levels at diagnosis (P=1.4 × 10(-5)). CONCLUSIONS: We confirmed that rs17632542 in KLK3 is associated with PSA at diagnosis. No significant association was seen between loci and disease-specific end points when accounting for multiple testing. This provides further evidence that known PCa risk SNPs do not predict likelihood of disease progression.
Keywords: genetics; mortality; prostate specific antigen; genetic predisposition to disease; prostate-specific antigen; prostatic neoplasms; prostate tumor; genetic predisposition; humans; human; male
Journal Title: British Journal of Cancer
Volume: 113
Issue: 1
ISSN: 0007-0920
Publisher: Nature Publishing Group  
Date Published: 2015-06-30
Start Page: 166
End Page: 172
Language: English
DOI: 10.1038/bjc.2015.199
PUBMED: 26068399
PROVIDER: scopus
PMCID: PMC4647539
DOI/URL:
Notes: Export Date: 2 October 2015 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Kenneth Offit
    495 Offit
  2. Peter T Scardino
    615 Scardino
  3. Hans Gosta Lilja
    280 Lilja
  4. James Eastham
    422 Eastham
  5. Robert J. Klein
    59 Klein
  6. Vijai Joseph
    113 Joseph
  7. Howard Scher
    771 Scher
  8. James E Hayes
    6 Hayes
  9. Marina Julia Corines
    13 Corines
  10. Tinu Mary Thomas
    15 Thomas
  11. Ryan P Kopp
    7 Kopp
  12. Anne Gunning Lincoln
    14 Lincoln
  13. Asad   Ashraf
    6 Ashraf