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Association of Reported Prostate Cancer Risk Alleles With PSA Levels Among Men Without a Diagnosis of Prostate Cancer

Wiklund, Fredrik; Zheng, S. Lilly; Sun, Jielin; Adami, Hans-Olov; Lilja, Hans LU ; Hsu, Fang-Chi; Stattin, Par; Adolfsson, Jan; Cramer, Scott D. and Duggan, David, et al. (2009) In The Prostate 69(4). p.419-427
Abstract
BACKGROUND. Prostate specific antigen (PSA) is widely used for prostate cancer screening but its levels are influenced by many non cancer-related factors. The goal of the study is to estimate the effect of genetic variants on PSA levels. METHODS. We evaluated the association of SNPs that were reported to be associated with prostate cancer risk in recent genome-wide association studies with plasma PSA levels in a Swedish study population, including 1,722 control subjects without a diagnosis of prostate cancer. RESULTS. Of the 16 SNPs analyzed in control subjects, significant associations with PSA levels (P <= 0.05) were found for six SNPs. These six SNP's had a cumulative effect on PSA levels; the mean PSA levels in men were almost... (More)
BACKGROUND. Prostate specific antigen (PSA) is widely used for prostate cancer screening but its levels are influenced by many non cancer-related factors. The goal of the study is to estimate the effect of genetic variants on PSA levels. METHODS. We evaluated the association of SNPs that were reported to be associated with prostate cancer risk in recent genome-wide association studies with plasma PSA levels in a Swedish study population, including 1,722 control subjects without a diagnosis of prostate cancer. RESULTS. Of the 16 SNPs analyzed in control subjects, significant associations with PSA levels (P <= 0.05) were found for six SNPs. These six SNP's had a cumulative effect on PSA levels; the mean PSA levels in men were almost twofold increased across increasing quintile of number of PSA associated alleles, P-trend = 3.4 x 10(-14). In this Swedish study population risk allele frequencies were similar among T1c case patients (cancer detected by elevated PSA levels alone) as compared to T2 and above prostate cancer case patients. CONCLUSIONS. Results from this study may have two important clinical implications. The cumulative effect of six SNPs on PSA levels suggests genetic-specific PSA cutoff values may be used to improve the discriminatory performance of this test for prostate cancer; and the dual associations of these SNPs with PSA levels and prostate cancer risk raise a concern that some of reported prostate cancer risk-associated SNPs may be confounded by the prevalent use of PSA screening. Prostate 69: 419-427, 2009. (C) 2008 Wiley-Liss, Inc. (Less)
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Contribution to journal
publication status
published
subject
keywords
KLK3, genetic, bias
in
The Prostate
volume
69
issue
4
pages
419 - 427
publisher
John Wiley & Sons
external identifiers
  • wos:000263546000010
  • scopus:59849113506
ISSN
0270-4137
DOI
10.1002/pros.20908
language
English
LU publication?
yes
id
d5e9eb78-bb4f-4b39-8d98-b057a9e6463d (old id 1372055)
date added to LUP
2009-05-07 14:40:39
date last changed
2017-09-17 05:32:27
@article{d5e9eb78-bb4f-4b39-8d98-b057a9e6463d,
  abstract     = {BACKGROUND. Prostate specific antigen (PSA) is widely used for prostate cancer screening but its levels are influenced by many non cancer-related factors. The goal of the study is to estimate the effect of genetic variants on PSA levels. METHODS. We evaluated the association of SNPs that were reported to be associated with prostate cancer risk in recent genome-wide association studies with plasma PSA levels in a Swedish study population, including 1,722 control subjects without a diagnosis of prostate cancer. RESULTS. Of the 16 SNPs analyzed in control subjects, significant associations with PSA levels (P &lt;= 0.05) were found for six SNPs. These six SNP's had a cumulative effect on PSA levels; the mean PSA levels in men were almost twofold increased across increasing quintile of number of PSA associated alleles, P-trend = 3.4 x 10(-14). In this Swedish study population risk allele frequencies were similar among T1c case patients (cancer detected by elevated PSA levels alone) as compared to T2 and above prostate cancer case patients. CONCLUSIONS. Results from this study may have two important clinical implications. The cumulative effect of six SNPs on PSA levels suggests genetic-specific PSA cutoff values may be used to improve the discriminatory performance of this test for prostate cancer; and the dual associations of these SNPs with PSA levels and prostate cancer risk raise a concern that some of reported prostate cancer risk-associated SNPs may be confounded by the prevalent use of PSA screening. Prostate 69: 419-427, 2009. (C) 2008 Wiley-Liss, Inc.},
  author       = {Wiklund, Fredrik and Zheng, S. Lilly and Sun, Jielin and Adami, Hans-Olov and Lilja, Hans and Hsu, Fang-Chi and Stattin, Par and Adolfsson, Jan and Cramer, Scott D. and Duggan, David and Carpten, John D. and Chang, Bao-Li and Isaacs, William B. and Gronberg, Henrik and Xu, Jianfeng},
  issn         = {0270-4137},
  keyword      = {KLK3,genetic,bias},
  language     = {eng},
  number       = {4},
  pages        = {419--427},
  publisher    = {John Wiley & Sons},
  series       = {The Prostate},
  title        = {Association of Reported Prostate Cancer Risk Alleles With PSA Levels Among Men Without a Diagnosis of Prostate Cancer},
  url          = {http://dx.doi.org/10.1002/pros.20908},
  volume       = {69},
  year         = {2009},
}