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.