Allelic loss of the loci containing the androgen synthesis gene, StAR, is prognostic for relapse in intermediate-risk prostate cancer

Jennifer A. Locke, Gaetano Zafarana, Chad A. Malloff, Wan L. Lam, Jenna Sykes, Melania Pintilie, Varune Rohan Ramnarine, Alice Meng, Omer Ahmed, Igor Jurisica, Emma Tomlinson Guns, Theo Van Der Kwast, Michael Milosevic, Robert G. Bristow

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND Androgen deprivation therapy (ADT) and novel agents targeting the androgen synthesis axis (e.g., abiraterone acetate) are adjuvant therapies that are currently, or may in the future be, combined with radiotherapy to reduce the chance of disease relapse. Little is known about allelic loss or gain pertaining to genes associated with the androgen synthesis axis and whether this is prognostic in patients who receive localized radiotherapy. In this hypothesis generating study, we conducted an array comparative genomic hybridization (aCGH) analysis of 33 androgen synthesis genes to identify potential prognostic factors for radiotherapy outcome. METHODS aCGH analysis of tumor DNA prospectively derived from frozen needle biopsies of 126 men with intermediate-risk disease who underwent image-guided radiotherapy (IGRT) to a mean dose of 76.4 Gy was conducted. Statistical analyses were conducted for allelic loss or gain in genes as potential prognostic factors relative to prostate specific antigen, Gleason-score, and T-category. RESULTS We observed that allelic losses of loci containing the genes StAR and HSD17B2 were associated with increased genetic instability (as determined by percentage genome alteration). On multivariate analyses these loci were prognostic for biochemical disease-free relapse (StAR: HR = 2.84, 95% CI: 1.44-5.61, P = 0.00269; HSD17B2: HR = 1.97, 95% CI: 1.06-3.64, P = 0.031). The results were validated in a surgical cohort of 131 intermediate-risk patients. CONCLUSIONS Allelic losses of the loci containing StAR and HSD17B2 have significant prognostic value for intermediate-risk prostate cancer. With this hypothesis generating information future studies should test StAR and HSD17B2 losses as biomarkers of androgen response in combined modality protocols.

Original languageEnglish
Pages (from-to)1295-1305
Number of pages11
JournalProstate
Volume72
Issue number12
DOIs
Publication statusPublished - 1 Sept 2012

Keywords

  • aCGH
  • androgen synthesis
  • diagnostic biopsies
  • Gleason-score
  • HSD17B2
  • prostate cancer
  • radiotherapy
  • StAR

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre

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