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

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Author

  • Fredrik Wiklund
  • S. Lilly Zheng
  • Jielin Sun
  • Hans-Olov Adami
  • Hans Lilja
  • Fang-Chi Hsu
  • Par Stattin
  • Jan Adolfsson
  • Scott D. Cramer
  • David Duggan
  • John D. Carpten
  • Bao-Li Chang
  • William B. Isaacs
  • Henrik Gronberg
  • Jianfeng Xu
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Summary, in English

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.

Publishing year

2009

Language

English

Pages

419-427

Publication/Series

The Prostate

Volume

69

Issue

4

Document type

Journal article

Publisher

John Wiley & Sons Inc.

Topic

  • Obstetrics, Gynecology and Reproductive Medicine

Keywords

  • KLK3
  • genetic
  • bias

Status

Published

Research group

  • Clinical Chemistry, Malmö

ISBN/ISSN/Other

  • ISSN: 0270-4137