Association of reported prostate cancer risk alleles with PSA levels among men without a diagnosis of prostate cancer

Fredrik Wiklund, S. Lilly Zheng, Jielin Sun, Hans Olov Adami, Hans Lilja, Fang Chi Hsu, Pär Stattin, Jan Adolfsson, Scott D. Cramer, David Duggan, John D. Carpten, Bao Li Chang, William B Isaacs, Henrik Grönberg, Jianfeng Xu

Research output: Contribution to journalArticle

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 SNPs 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 × 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.

Original languageEnglish (US)
Pages (from-to)419-427
Number of pages9
JournalProstate
Volume69
Issue number4
DOIs
StatePublished - Mar 1 2009

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Prostate-Specific Antigen
Prostatic Neoplasms
Alleles
Single Nucleotide Polymorphism
Genome-Wide Association Study
Early Detection of Cancer
Gene Frequency
Population
Neoplasms

Keywords

  • Bias
  • Genetic
  • KLK3

ASJC Scopus subject areas

  • Urology
  • Oncology
  • Medicine(all)

Cite this

Wiklund, F., Zheng, S. L., Sun, J., Adami, H. O., Lilja, H., Hsu, F. C., ... Xu, J. (2009). Association of reported prostate cancer risk alleles with PSA levels among men without a diagnosis of prostate cancer. Prostate, 69(4), 419-427. https://doi.org/10.1002/pros.20908

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; Hsu, Fang Chi; Stattin, Pär; Adolfsson, Jan; Cramer, Scott D.; Duggan, David; Carpten, John D.; Chang, Bao Li; Isaacs, William B; Grönberg, Henrik; Xu, Jianfeng.

In: Prostate, Vol. 69, No. 4, 01.03.2009, p. 419-427.

Research output: Contribution to journalArticle

Wiklund, F, Zheng, SL, Sun, J, Adami, HO, Lilja, H, Hsu, FC, Stattin, P, Adolfsson, J, Cramer, SD, Duggan, D, Carpten, JD, Chang, BL, Isaacs, WB, Grönberg, H & Xu, J 2009, 'Association of reported prostate cancer risk alleles with PSA levels among men without a diagnosis of prostate cancer', Prostate, vol. 69, no. 4, pp. 419-427. https://doi.org/10.1002/pros.20908
Wiklund, Fredrik ; Zheng, S. Lilly ; Sun, Jielin ; Adami, Hans Olov ; Lilja, Hans ; Hsu, Fang Chi ; Stattin, Pär ; Adolfsson, Jan ; Cramer, Scott D. ; Duggan, David ; Carpten, John D. ; Chang, Bao Li ; Isaacs, William B ; Grönberg, Henrik ; Xu, Jianfeng. / Association of reported prostate cancer risk alleles with PSA levels among men without a diagnosis of prostate cancer. In: Prostate. 2009 ; Vol. 69, No. 4. pp. 419-427.
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AU - Hsu, Fang Chi

AU - Stattin, Pär

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