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.
Highlights
Vasectomy is a simple surgical procedure used for male sterilization
Prostatic intraepithelial neoplasia (PIN) lesions were seen in all the mice in both groups even at 10 weeks, while adenocarcinoma was eventually found in all of them by 24 weeks
Appropriate approval from the Institutional Review Board (#29646), including the request to waive the documentation of informed consent from the patients, was obtained before construction of the tissue microarray (TMA) consisting of representative lesions of non-neoplastic normal-appearing prostate, high-grade PIN (HGPIN), and prostatic adenocarcinoma, as we described previously [27,28]
Summary
Vasectomy is a simple surgical procedure used for male sterilization. From the National Survey of Family Growth in the United States, at least 500,000 American men were estimated to annually undergo vasectomy as their permanent form of contraception [1,2]. A substantial number of cohort and case-control studies have shown an elevated risk of prostate cancer in men who have undergone vasectomy, with an odds ratio (OR) up to 5.3 in US studies (Figure S1) [4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25].
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