An analysis of the association between prostate cancer risk loci, PSA levels, disease aggressiveness and disease-specific mortality
(2015) In British Journal of Cancer 113. p.166-172- 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... (More)
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.
(Less)
- author
- 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.
LU
; Scardino, P.
; Eastham, J.
; Offit, K.
; Vijai, J.
and Klein, R. J.
(Less) - publishing date
- 2015-06-30
- type
- Contribution to journal
- publication status
- published
- keywords
- biochemical recurrence, biomarkers, castrate metastasis, disease-specific mortality, Prostate cancer, single-nucleotide polymorphisms
- in
- British Journal of Cancer
- volume
- 113
- pages
- 166 - 172
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:26068399
- scopus:84934272049
- ISSN
- 0007-0920
- DOI
- 10.1038/bjc.2015.199
- language
- English
- LU publication?
- no
- additional info
- Publisher Copyright: © 2015 Cancer Research UK. All rights reserved.
- id
- 2f1e0192-d24b-4d82-a342-454cba5454a1
- date added to LUP
- 2022-12-06 14:16:01
- date last changed
- 2024-01-18 18:11:47
@article{2f1e0192-d24b-4d82-a342-454cba5454a1,
abstract = {{<p>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<sup>-5</sup>).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.</p>}},
author = {{Sullivan, J. and Kopp, R. and Stratton, K. and Manschreck, C. and Corines, M. and Rau-Murthy, R. and Hayes, J. and Lincon, A. and Ashraf, A. and Thomas, T. and Schrader, K. and Gallagher, D. and Hamilton, R. and Scher, H. and Lilja, H. and Scardino, P. and Eastham, J. and Offit, K. and Vijai, J. and Klein, R. J.}},
issn = {{0007-0920}},
keywords = {{biochemical recurrence; biomarkers; castrate metastasis; disease-specific mortality; Prostate cancer; single-nucleotide polymorphisms}},
language = {{eng}},
month = {{06}},
pages = {{166--172}},
publisher = {{Nature Publishing Group}},
series = {{British Journal of Cancer}},
title = {{An analysis of the association between prostate cancer risk loci, PSA levels, disease aggressiveness and disease-specific mortality}},
url = {{http://dx.doi.org/10.1038/bjc.2015.199}},
doi = {{10.1038/bjc.2015.199}},
volume = {{113}},
year = {{2015}},
}