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

J. Sullivan, Ryan Kopp, K. Stratton, C. Manschreck, M. Corines, R. Rau-Murthy, J. Hayes, A. Lincon, A. Ashraf, T. Thomas, K. Schrader, D. Gallagher, R. Hamilton, H. Scher, H. Lilja, P. Scardino, J. Eastham, K. Offit, J. Vijai, R. J. Klein

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)166-172
Number of pages7
JournalBritish Journal of Cancer
Volume113
Issue number1
DOIs
StatePublished - Jun 30 2015
Externally publishedYes

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Prostatic Neoplasms
Nucleotides
Mortality
Alleles
Neoplasm Metastasis
Recurrence
Genome-Wide Association Study
Disease Progression

Keywords

  • biochemical recurrence
  • biomarkers
  • castrate metastasis
  • disease-specific mortality
  • Prostate cancer
  • single-nucleotide polymorphisms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

An analysis of the association between prostate cancer risk loci, PSA levels, disease aggressiveness and disease-specific mortality. / Sullivan, J.; Kopp, Ryan; Stratton, K.; Manschreck, C.; Corines, M.; Rau-Murthy, R.; Hayes, J.; Lincon, 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.

In: British Journal of Cancer, Vol. 113, No. 1, 30.06.2015, p. 166-172.

Research output: Contribution to journalArticle

Sullivan, J, Kopp, R, Stratton, K, Manschreck, C, Corines, M, Rau-Murthy, R, Hayes, J, Lincon, A, Ashraf, A, Thomas, T, Schrader, K, Gallagher, D, Hamilton, R, Scher, H, Lilja, H, Scardino, P, Eastham, J, Offit, K, Vijai, J & Klein, RJ 2015, 'An analysis of the association between prostate cancer risk loci, PSA levels, disease aggressiveness and disease-specific mortality', British Journal of Cancer, vol. 113, no. 1, pp. 166-172. https://doi.org/10.1038/bjc.2015.199a
Sullivan, J. ; Kopp, Ryan ; Stratton, K. ; Manschreck, C. ; Corines, M. ; Rau-Murthy, R. ; Hayes, J. ; Lincon, 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. / An analysis of the association between prostate cancer risk loci, PSA levels, disease aggressiveness and disease-specific mortality. In: British Journal of Cancer. 2015 ; Vol. 113, No. 1. pp. 166-172.
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AU - Sullivan, J.

AU - Kopp, Ryan

AU - Stratton, K.

AU - Manschreck, C.

AU - Corines, M.

AU - Rau-Murthy, R.

AU - Hayes, J.

AU - Lincon, A.

AU - Ashraf, A.

AU - Thomas, T.

AU - Schrader, K.

AU - Gallagher, D.

AU - Hamilton, R.

AU - Scher, H.

AU - Lilja, H.

AU - Scardino, P.

AU - Eastham, J.

AU - Offit, K.

AU - Vijai, J.

AU - Klein, R. J.

PY - 2015/6/30

Y1 - 2015/6/30

N2 - 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.

AB - 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.

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