Association of prostate cancer risk alleles with unfavourable pathological characteristics in potential candidates for active surveillance

Barry B. McGuire, Brian T. Helfand, Shilajit D Kundu, Qiaoyan Hu, Jessica A. Banks, Phillip Cooper, William J Catalona*

*Corresponding author for this work

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Study Type - Prognosis (cohort) Level of Evidence 2a What's known on the subject? and What does the study add? Men fail active surveillance for a variety of reasons; however, no single reliable biomarker has been found to date which will identify these men from the outset. We know that there are about 35 prostate cancer risk alleles which have been discovered to influence risk of prostate cancer, from large-scale genome-wide association studies. Some of these have been associated with aggressive prostate cancer. Nobody has examined the potential for these risk alleles to predict men who might fail active surveillance. This study adds to the growing evidence that single nucleotide polymorphisms may be able to identify men who have aggressive prostate cancers, and that this could be part of a risk algorithm used in active surveillance protocols. OBJECTIVE To assess whether the carrier status of 35 risk alleles for prostate cancer (CaP) is associated with having unfavourable pathological features in the radical prostatectomy specimen in men with clinically low risk CaP who fulfil commonly accepted criteria as candidates for active surveillance. PATIENTS AND METHODS We studied men of European ancestry with CaP who fulfilled the commonly accepted clinical criteria for active surveillance (T1c, prostate-specific antigen <10 ng/mL, biopsy Gleason ≤6, three or fewer positive cores, a;circ50% tumour involvement/core) but instead underwent early radical prostatectomy. We genotyped these men for 35 CaP risk alleles. We defined 'unfavourable' pathological characteristics to be Gleason ≥7 and/or ≥ pT2b in their radical prostatectomy specimen. RESULTS In all, 263 men (median age 60 [46-72] years) fulfilled our selection criteria for active surveillance, and 58 of 263 (22.1%) were found to have 'unfavourable' pathological characteristics. The frequencies of three CaP risk alleles (rs1447295 [8q24], P= 0.004; rs1571801 [9q33.2], P= 0.03; rs11228565 [11q13], P= 0.02) were significantly higher in men with 'unfavourable' pathological characteristics. Two other risk alleles were proportionately more frequent (rs10934853 [3q21], P= 0.06; rs1859962 [17q24], P= 0.07) but did not achieve nominal statistical significance. Carriers of any one of the significantly over-represented risk alleles had twice the likelihood of unfavourable tumour features (P= 0.03), and carriers of any two had a sevenfold increased likelihood (P= 0.001). Receiver-operator curve analysis demonstrated an area under the curve of 0.66, suggesting that the number of single nucleotide polymorphisms carried provided discrimination between men with 'favourable' and 'unfavourable' tumour features in their prostatectomy specimen. CONCLUSION In potential candidates for active surveillance, certain CaP risk alleles are more prevalent in patients with 'unfavourable' pathological characteristics in their radical prostatectomy specimen.

Original languageEnglish (US)
Pages (from-to)338-343
Number of pages6
JournalBJU International
Volume110
Issue number3
DOIs
StatePublished - Aug 1 2012

Fingerprint

Prostatic Neoplasms
Alleles
Prostatectomy
Single Nucleotide Polymorphism
Neoplasms
Genome-Wide Association Study
Prostate-Specific Antigen
Patient Selection
Area Under Curve
Biomarkers
Biopsy

Keywords

  • active surveillance
  • prostate cancer
  • risk allele
  • single nucleotide polymorphism

ASJC Scopus subject areas

  • Urology

Cite this

McGuire, Barry B. ; Helfand, Brian T. ; Kundu, Shilajit D ; Hu, Qiaoyan ; Banks, Jessica A. ; Cooper, Phillip ; Catalona, William J. / Association of prostate cancer risk alleles with unfavourable pathological characteristics in potential candidates for active surveillance. In: BJU International. 2012 ; Vol. 110, No. 3. pp. 338-343.
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abstract = "Study Type - Prognosis (cohort) Level of Evidence 2a What's known on the subject? and What does the study add? Men fail active surveillance for a variety of reasons; however, no single reliable biomarker has been found to date which will identify these men from the outset. We know that there are about 35 prostate cancer risk alleles which have been discovered to influence risk of prostate cancer, from large-scale genome-wide association studies. Some of these have been associated with aggressive prostate cancer. Nobody has examined the potential for these risk alleles to predict men who might fail active surveillance. This study adds to the growing evidence that single nucleotide polymorphisms may be able to identify men who have aggressive prostate cancers, and that this could be part of a risk algorithm used in active surveillance protocols. OBJECTIVE To assess whether the carrier status of 35 risk alleles for prostate cancer (CaP) is associated with having unfavourable pathological features in the radical prostatectomy specimen in men with clinically low risk CaP who fulfil commonly accepted criteria as candidates for active surveillance. PATIENTS AND METHODS We studied men of European ancestry with CaP who fulfilled the commonly accepted clinical criteria for active surveillance (T1c, prostate-specific antigen <10 ng/mL, biopsy Gleason ≤6, three or fewer positive cores, a;circ50{\%} tumour involvement/core) but instead underwent early radical prostatectomy. We genotyped these men for 35 CaP risk alleles. We defined 'unfavourable' pathological characteristics to be Gleason ≥7 and/or ≥ pT2b in their radical prostatectomy specimen. RESULTS In all, 263 men (median age 60 [46-72] years) fulfilled our selection criteria for active surveillance, and 58 of 263 (22.1{\%}) were found to have 'unfavourable' pathological characteristics. The frequencies of three CaP risk alleles (rs1447295 [8q24], P= 0.004; rs1571801 [9q33.2], P= 0.03; rs11228565 [11q13], P= 0.02) were significantly higher in men with 'unfavourable' pathological characteristics. Two other risk alleles were proportionately more frequent (rs10934853 [3q21], P= 0.06; rs1859962 [17q24], P= 0.07) but did not achieve nominal statistical significance. Carriers of any one of the significantly over-represented risk alleles had twice the likelihood of unfavourable tumour features (P= 0.03), and carriers of any two had a sevenfold increased likelihood (P= 0.001). Receiver-operator curve analysis demonstrated an area under the curve of 0.66, suggesting that the number of single nucleotide polymorphisms carried provided discrimination between men with 'favourable' and 'unfavourable' tumour features in their prostatectomy specimen. CONCLUSION In potential candidates for active surveillance, certain CaP risk alleles are more prevalent in patients with 'unfavourable' pathological characteristics in their radical prostatectomy specimen.",
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Association of prostate cancer risk alleles with unfavourable pathological characteristics in potential candidates for active surveillance. / McGuire, Barry B.; Helfand, Brian T.; Kundu, Shilajit D; Hu, Qiaoyan; Banks, Jessica A.; Cooper, Phillip; Catalona, William J.

In: BJU International, Vol. 110, No. 3, 01.08.2012, p. 338-343.

Research output: Contribution to journalArticle

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T1 - Association of prostate cancer risk alleles with unfavourable pathological characteristics in potential candidates for active surveillance

AU - McGuire, Barry B.

AU - Helfand, Brian T.

AU - Kundu, Shilajit D

AU - Hu, Qiaoyan

AU - Banks, Jessica A.

AU - Cooper, Phillip

AU - Catalona, William J

PY - 2012/8/1

Y1 - 2012/8/1

N2 - Study Type - Prognosis (cohort) Level of Evidence 2a What's known on the subject? and What does the study add? Men fail active surveillance for a variety of reasons; however, no single reliable biomarker has been found to date which will identify these men from the outset. We know that there are about 35 prostate cancer risk alleles which have been discovered to influence risk of prostate cancer, from large-scale genome-wide association studies. Some of these have been associated with aggressive prostate cancer. Nobody has examined the potential for these risk alleles to predict men who might fail active surveillance. This study adds to the growing evidence that single nucleotide polymorphisms may be able to identify men who have aggressive prostate cancers, and that this could be part of a risk algorithm used in active surveillance protocols. OBJECTIVE To assess whether the carrier status of 35 risk alleles for prostate cancer (CaP) is associated with having unfavourable pathological features in the radical prostatectomy specimen in men with clinically low risk CaP who fulfil commonly accepted criteria as candidates for active surveillance. PATIENTS AND METHODS We studied men of European ancestry with CaP who fulfilled the commonly accepted clinical criteria for active surveillance (T1c, prostate-specific antigen <10 ng/mL, biopsy Gleason ≤6, three or fewer positive cores, a;circ50% tumour involvement/core) but instead underwent early radical prostatectomy. We genotyped these men for 35 CaP risk alleles. We defined 'unfavourable' pathological characteristics to be Gleason ≥7 and/or ≥ pT2b in their radical prostatectomy specimen. RESULTS In all, 263 men (median age 60 [46-72] years) fulfilled our selection criteria for active surveillance, and 58 of 263 (22.1%) were found to have 'unfavourable' pathological characteristics. The frequencies of three CaP risk alleles (rs1447295 [8q24], P= 0.004; rs1571801 [9q33.2], P= 0.03; rs11228565 [11q13], P= 0.02) were significantly higher in men with 'unfavourable' pathological characteristics. Two other risk alleles were proportionately more frequent (rs10934853 [3q21], P= 0.06; rs1859962 [17q24], P= 0.07) but did not achieve nominal statistical significance. Carriers of any one of the significantly over-represented risk alleles had twice the likelihood of unfavourable tumour features (P= 0.03), and carriers of any two had a sevenfold increased likelihood (P= 0.001). Receiver-operator curve analysis demonstrated an area under the curve of 0.66, suggesting that the number of single nucleotide polymorphisms carried provided discrimination between men with 'favourable' and 'unfavourable' tumour features in their prostatectomy specimen. CONCLUSION In potential candidates for active surveillance, certain CaP risk alleles are more prevalent in patients with 'unfavourable' pathological characteristics in their radical prostatectomy specimen.

AB - Study Type - Prognosis (cohort) Level of Evidence 2a What's known on the subject? and What does the study add? Men fail active surveillance for a variety of reasons; however, no single reliable biomarker has been found to date which will identify these men from the outset. We know that there are about 35 prostate cancer risk alleles which have been discovered to influence risk of prostate cancer, from large-scale genome-wide association studies. Some of these have been associated with aggressive prostate cancer. Nobody has examined the potential for these risk alleles to predict men who might fail active surveillance. This study adds to the growing evidence that single nucleotide polymorphisms may be able to identify men who have aggressive prostate cancers, and that this could be part of a risk algorithm used in active surveillance protocols. OBJECTIVE To assess whether the carrier status of 35 risk alleles for prostate cancer (CaP) is associated with having unfavourable pathological features in the radical prostatectomy specimen in men with clinically low risk CaP who fulfil commonly accepted criteria as candidates for active surveillance. PATIENTS AND METHODS We studied men of European ancestry with CaP who fulfilled the commonly accepted clinical criteria for active surveillance (T1c, prostate-specific antigen <10 ng/mL, biopsy Gleason ≤6, three or fewer positive cores, a;circ50% tumour involvement/core) but instead underwent early radical prostatectomy. We genotyped these men for 35 CaP risk alleles. We defined 'unfavourable' pathological characteristics to be Gleason ≥7 and/or ≥ pT2b in their radical prostatectomy specimen. RESULTS In all, 263 men (median age 60 [46-72] years) fulfilled our selection criteria for active surveillance, and 58 of 263 (22.1%) were found to have 'unfavourable' pathological characteristics. The frequencies of three CaP risk alleles (rs1447295 [8q24], P= 0.004; rs1571801 [9q33.2], P= 0.03; rs11228565 [11q13], P= 0.02) were significantly higher in men with 'unfavourable' pathological characteristics. Two other risk alleles were proportionately more frequent (rs10934853 [3q21], P= 0.06; rs1859962 [17q24], P= 0.07) but did not achieve nominal statistical significance. Carriers of any one of the significantly over-represented risk alleles had twice the likelihood of unfavourable tumour features (P= 0.03), and carriers of any two had a sevenfold increased likelihood (P= 0.001). Receiver-operator curve analysis demonstrated an area under the curve of 0.66, suggesting that the number of single nucleotide polymorphisms carried provided discrimination between men with 'favourable' and 'unfavourable' tumour features in their prostatectomy specimen. CONCLUSION In potential candidates for active surveillance, certain CaP risk alleles are more prevalent in patients with 'unfavourable' pathological characteristics in their radical prostatectomy specimen.

KW - active surveillance

KW - prostate cancer

KW - risk allele

KW - single nucleotide polymorphism

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