Impact of Vasectomy on the Development and Progression of Prostate Cancer: Preclinical Evidence

  • Cancers (Basel). 2020 Aug 15;12(8):2295. doi: 10.3390/cancers12082295.
Takashi Kawahara  1  2  3  4 ,  Yuki Teramoto  1  5 ,  Yi Li  1 ,  Hitoshi Ishiguro  1  2  3  6  7 ,  Jennifer Gordetsky  1  8  9 ,  Zhiming Yang  1 ,  Hiroshi Miyamoto  1  2  3  5  8
Affiliations
  • 1. Department of Pathology & Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA.
  • 2. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • 3. James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • 4. Departments of Urology and Renal Transplantation, Yokohama City University Medical Center, Yokohama 232-0024, Japan.
  • 5. James P. Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY 14642, USA.
  • 6. Kanagawa Institute of Industrial Science and Technology, Kawasaki 210-0821, Japan.
  • 7. Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
  • 8. Department of Urology, University of Rochester Medical Center, Rochester, NY 14642, USA.
  • 9. Departments of Pathology and Urology, Vanderbilt University Medical Center, Nashville, TN 37212, USA.
PMID: 32824199 DOI: 10.3390/cancers12082295
Abstract

Some observational studies have implied a link between vasectomy and an elevated risk of Prostate Cancer. We investigated the impact of vasectomy on Prostate Cancer outgrowth, mainly using preclinical models. Neoplastic changes in the prostate were compared in transgenic TRAMP mice that underwent vasectomy vs. sham surgery performed at 4 weeks of age. One of the molecules identified by DNA microarray (i.e., ZKSCAN3) was then assessed in radical prostatectomy specimens and human Prostate Cancer lines. At 24 weeks, gross tumor (p = 0.089) and poorly differentiated adenocarcinoma (p = 0.036) occurred more often in vasectomized mice. Vasectomy significantly induced ZKSCAN3 expression in prostate tissues from C57BL/6 mice and prostate cancers from TRAMP mice. Immunohistochemistry showed increased ZKSCAN3 expression in adenocarcinoma vs. prostatic intraepithelial neoplasia (PIN), PIN vs. non-neoplastic prostate, Grade Group ≥3 vs. ≤2 Tumors, pT3 vs. pT2 Tumors, pN1 vs. pN0 Tumors, and Prostate Cancer from patients with a history of vasectomy. Additionally, strong (2+/3+) ZKSCAN3 expression (p = 0.002), as an independent prognosticator, or vasectomy (p = 0.072) was associated with the risk of tumor recurrence. In Prostate Cancer lines, ZKSCAN3 silencing resulted in significant decreases in cell proliferation/migration/invasion. These findings suggest that there might be an association between vasectomy and the development and progression of Prostate Cancer, with up-regulation of ZKSCAN3 expression as a potential underlying mechanism.

Keywords
TRAMP model; ZKSCAN3; immunohistochemistry; prostate cancer; vasectomy.