Association of prostate cancer risk variants with clinicopathologic characteristics of the disease

Jianfeng Xu, Sarah D. Isaacs, Jielin Sun, Ge Li, Kathleen E. Wiley, Yi Zhu, Fang Chi Hsu, Fredrik Wiklund, Aubrey R. Turner, Tamara S. Adams, Wennuan Liu, Bruce Trock, Alan Wayne Partin, Baoli Chang, Patrick Walsh, Henrik Grönberg, William B Isaacs, Siqun Zheng

Research output: Contribution to journalArticle

Abstract

Purpose: Fifteen independent genetic variants have been implicated in prostate cancer risk by recent genome-wide association studies. However, their association with clinicopathologic features of prostate cancer is uncertain. Experimental Design: We systematically evaluated these 15 variants in 1,563 prostate cancer patients undergoing radical prostatectomy, taking advantage of the uniform tumor stage and grade information available for each of these cases. Associations of these variants with aggressiveness, pathologic Gleason scores, pathologic stage, age at diagnosis, or serum prostatespecific antigen (PSA) levels were tested. Results: After adjusting for multiple testing, none of the single nucleotide polymorphisms was individually or cumulatively associated with aggressiveness or individual clinicopathologic variables of prostate cancer such as Gleason scores, pathologic stage, or age at diagnosis of prostate cancer. The reported risk allele (G) for single nucleotide polymorphism rs2735839 in the KLK3 gene at 19q13 was more frequent in less aggressive prostate cancer patients (0.89) than in more aggressive prostate cancer patients (0.86; nominal P = 0.03) or in controls (0.86; nominal P = 0.04). Considering that this allele was also significantly associated with higher serum PSA levels among controls (nominal P = 0.003), the observed trend of higher frequency of this risk allele between less and more aggressive prostate cancer, or between less aggressive and controls may be due to detection bias of PSA screening. Conclusions: Prostate cancer risk variants recently discovered from genome-wide case-control association studies are not associated with clinicopathologic variables in this population. Casecase studies are urgently needed to discover genetic variants that predict tumor aggressiveness.

Original languageEnglish (US)
Pages (from-to)5819-5824
Number of pages6
JournalClinical Cancer Research
Volume14
Issue number18
DOIs
StatePublished - Sep 15 2008

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Prostatic Neoplasms
Neoplasm Grading
Antigens
Single Nucleotide Polymorphism
Alleles
Genome-Wide Association Study
Prostatectomy
Serum
Gene Frequency
Case-Control Studies
Neoplasms
Research Design
Genome
Population
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Association of prostate cancer risk variants with clinicopathologic characteristics of the disease. / Xu, Jianfeng; Isaacs, Sarah D.; Sun, Jielin; Li, Ge; Wiley, Kathleen E.; Zhu, Yi; Hsu, Fang Chi; Wiklund, Fredrik; Turner, Aubrey R.; Adams, Tamara S.; Liu, Wennuan; Trock, Bruce; Partin, Alan Wayne; Chang, Baoli; Walsh, Patrick; Grönberg, Henrik; Isaacs, William B; Zheng, Siqun.

In: Clinical Cancer Research, Vol. 14, No. 18, 15.09.2008, p. 5819-5824.

Research output: Contribution to journalArticle

Xu, J, Isaacs, SD, Sun, J, Li, G, Wiley, KE, Zhu, Y, Hsu, FC, Wiklund, F, Turner, AR, Adams, TS, Liu, W, Trock, B, Partin, AW, Chang, B, Walsh, P, Grönberg, H, Isaacs, WB & Zheng, S 2008, 'Association of prostate cancer risk variants with clinicopathologic characteristics of the disease', Clinical Cancer Research, vol. 14, no. 18, pp. 5819-5824. https://doi.org/10.1158/1078-0432.CCR-08-0934
Xu, Jianfeng ; Isaacs, Sarah D. ; Sun, Jielin ; Li, Ge ; Wiley, Kathleen E. ; Zhu, Yi ; Hsu, Fang Chi ; Wiklund, Fredrik ; Turner, Aubrey R. ; Adams, Tamara S. ; Liu, Wennuan ; Trock, Bruce ; Partin, Alan Wayne ; Chang, Baoli ; Walsh, Patrick ; Grönberg, Henrik ; Isaacs, William B ; Zheng, Siqun. / Association of prostate cancer risk variants with clinicopathologic characteristics of the disease. In: Clinical Cancer Research. 2008 ; Vol. 14, No. 18. pp. 5819-5824.
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abstract = "Purpose: Fifteen independent genetic variants have been implicated in prostate cancer risk by recent genome-wide association studies. However, their association with clinicopathologic features of prostate cancer is uncertain. Experimental Design: We systematically evaluated these 15 variants in 1,563 prostate cancer patients undergoing radical prostatectomy, taking advantage of the uniform tumor stage and grade information available for each of these cases. Associations of these variants with aggressiveness, pathologic Gleason scores, pathologic stage, age at diagnosis, or serum prostatespecific antigen (PSA) levels were tested. Results: After adjusting for multiple testing, none of the single nucleotide polymorphisms was individually or cumulatively associated with aggressiveness or individual clinicopathologic variables of prostate cancer such as Gleason scores, pathologic stage, or age at diagnosis of prostate cancer. The reported risk allele (G) for single nucleotide polymorphism rs2735839 in the KLK3 gene at 19q13 was more frequent in less aggressive prostate cancer patients (0.89) than in more aggressive prostate cancer patients (0.86; nominal P = 0.03) or in controls (0.86; nominal P = 0.04). Considering that this allele was also significantly associated with higher serum PSA levels among controls (nominal P = 0.003), the observed trend of higher frequency of this risk allele between less and more aggressive prostate cancer, or between less aggressive and controls may be due to detection bias of PSA screening. Conclusions: Prostate cancer risk variants recently discovered from genome-wide case-control association studies are not associated with clinicopathologic variables in this population. Casecase studies are urgently needed to discover genetic variants that predict tumor aggressiveness.",
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T1 - Association of prostate cancer risk variants with clinicopathologic characteristics of the disease

AU - Xu, Jianfeng

AU - Isaacs, Sarah D.

AU - Sun, Jielin

AU - Li, Ge

AU - Wiley, Kathleen E.

AU - Zhu, Yi

AU - Hsu, Fang Chi

AU - Wiklund, Fredrik

AU - Turner, Aubrey R.

AU - Adams, Tamara S.

AU - Liu, Wennuan

AU - Trock, Bruce

AU - Partin, Alan Wayne

AU - Chang, Baoli

AU - Walsh, Patrick

AU - Grönberg, Henrik

AU - Isaacs, William B

AU - Zheng, Siqun

PY - 2008/9/15

Y1 - 2008/9/15

N2 - Purpose: Fifteen independent genetic variants have been implicated in prostate cancer risk by recent genome-wide association studies. However, their association with clinicopathologic features of prostate cancer is uncertain. Experimental Design: We systematically evaluated these 15 variants in 1,563 prostate cancer patients undergoing radical prostatectomy, taking advantage of the uniform tumor stage and grade information available for each of these cases. Associations of these variants with aggressiveness, pathologic Gleason scores, pathologic stage, age at diagnosis, or serum prostatespecific antigen (PSA) levels were tested. Results: After adjusting for multiple testing, none of the single nucleotide polymorphisms was individually or cumulatively associated with aggressiveness or individual clinicopathologic variables of prostate cancer such as Gleason scores, pathologic stage, or age at diagnosis of prostate cancer. The reported risk allele (G) for single nucleotide polymorphism rs2735839 in the KLK3 gene at 19q13 was more frequent in less aggressive prostate cancer patients (0.89) than in more aggressive prostate cancer patients (0.86; nominal P = 0.03) or in controls (0.86; nominal P = 0.04). Considering that this allele was also significantly associated with higher serum PSA levels among controls (nominal P = 0.003), the observed trend of higher frequency of this risk allele between less and more aggressive prostate cancer, or between less aggressive and controls may be due to detection bias of PSA screening. Conclusions: Prostate cancer risk variants recently discovered from genome-wide case-control association studies are not associated with clinicopathologic variables in this population. Casecase studies are urgently needed to discover genetic variants that predict tumor aggressiveness.

AB - Purpose: Fifteen independent genetic variants have been implicated in prostate cancer risk by recent genome-wide association studies. However, their association with clinicopathologic features of prostate cancer is uncertain. Experimental Design: We systematically evaluated these 15 variants in 1,563 prostate cancer patients undergoing radical prostatectomy, taking advantage of the uniform tumor stage and grade information available for each of these cases. Associations of these variants with aggressiveness, pathologic Gleason scores, pathologic stage, age at diagnosis, or serum prostatespecific antigen (PSA) levels were tested. Results: After adjusting for multiple testing, none of the single nucleotide polymorphisms was individually or cumulatively associated with aggressiveness or individual clinicopathologic variables of prostate cancer such as Gleason scores, pathologic stage, or age at diagnosis of prostate cancer. The reported risk allele (G) for single nucleotide polymorphism rs2735839 in the KLK3 gene at 19q13 was more frequent in less aggressive prostate cancer patients (0.89) than in more aggressive prostate cancer patients (0.86; nominal P = 0.03) or in controls (0.86; nominal P = 0.04). Considering that this allele was also significantly associated with higher serum PSA levels among controls (nominal P = 0.003), the observed trend of higher frequency of this risk allele between less and more aggressive prostate cancer, or between less aggressive and controls may be due to detection bias of PSA screening. Conclusions: Prostate cancer risk variants recently discovered from genome-wide case-control association studies are not associated with clinicopathologic variables in this population. Casecase studies are urgently needed to discover genetic variants that predict tumor aggressiveness.

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