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

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.

SUBMITTER: Kawahara T

PROVIDER: S-EPMC7464827 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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

Kawahara Takashi T Teramoto Yuki Y Li Yi Y Ishiguro Hitoshi H Gordetsky Jennifer J Yang Zhiming Z Miyamoto Hiroshi H

Cancers 20200815 8

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 l ...[more]

PMID: 32824199

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Project description:ContextPrevious reports have shown an association between vasectomy and prostate cancer (PCa). However, there exist significant discrepancies between studies and systematic reviews due to a lack of strong causal association and residual confounding factors such as prostate-specific antigen (PSA) screening.ObjectiveTo assess the association between vasectomy and PCa, in both unadjusted and PSA screen-adjusted studies.Evidence acquisitionWe performed a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses. The PubMed, Scopus, and Web of Science databases were searched in January 2022 for studies that analyzed the association between vasectomy and PCa.Evidence synthesisA total of 37 studies including 16 931 805 patients met our inclusion criteria. A pooled analysis from all studies showed a significant association between vasectomy and any-grade PCa (odds ratio [OR] 1.23; 95% confidence interval [CI], 1.10-1.37; p < 0.001; I2 = 96%), localized PCa (OR 1.08; 95% CI, 1.06-1.11; p < 0.00001; I2 = 31%), or advanced PCa (OR 1.07; 95% CI, 1.02-1.13; p = 0.006; I2 = 0%). The association with PCa remained significant when the analyses were restricted to studies with a low risk of bias (OR 1.06; 95% CI, 1.02-1.10; p = 0.02; I2 = 48%) or cohort studies (OR 1.09; 95% CI, 1.04-1.13; p < 0.0001; I2 = 64%). Among studies adjusted for PSA screening, the association with localized PCa (OR 1.06; 95% CI, 1.03-1.09; p < 0.001; I2 = 0%) remained significant. Conversely, vasectomy was no longer associated with localized high-grade (p = 0.19), advanced (p = 0.22), and lethal (p = 0.42) PCa.ConclusionsOur meta-analysis found an association between vasectomy and any, mainly localized, PCa. However, the effect estimates of the association were increasingly close to null when examining studies of robust design and high quality. On exploratory analyses including studies, which adjusted for PSA screening, the association for aggressive and/or advanced PCa diminished.Patient summaryIn this study, we found an association between vasectomy and the risk of developing localized prostate cancer without being able to determine whether the procedure leads to a higher prostate cancer incidence.

Project description:ImportanceDespite 3 decades of study, there remains ongoing debate regarding whether vasectomy is associated with prostate cancer.ObjectiveTo determine if vasectomy is associated with prostate cancer.Data sourcesThe MEDLINE, EMBASE, Web of Science, and Scopus databases were searched for studies indexed from database inception to March 21, 2017, without language restriction.Study selectionCohort, case-control, and cross-sectional studies reporting relative effect estimates for the association between vasectomy and prostate cancer were included.Data extraction and synthesisTwo investigators performed study selection independently. Data were pooled separately by study design type using random-effects models. The Newcastle-Ottawa Scale was used to assess risk of bias.Main outcomes and measuresThe primary outcome was any diagnosis of prostate cancer. Secondary outcomes were high-grade, advanced, and fatal prostate cancer.ResultsFifty-three studies (16 cohort studies including 2 563 519 participants, 33 case-control studies including 44 536 participants, and 4 cross-sectional studies including 12 098 221 participants) were included. Of these, 7 cohort studies (44%), 26 case-control studies (79%), and all 4 cross-sectional studies were deemed to have a moderate to high risk of bias. Among studies deemed to have a low risk of bias, a weak association was found among cohort studies (7 studies; adjusted rate ratio, 1.05; 95% CI, 1.02-1.09; P < .001; I2 = 9%) and a similar but nonsignificant association was found among case-control studies (6 studies; adjusted odds ratio, 1.06; 95% CI, 0.88-1.29; P = .54; I2 = 37%). Effect estimates were further from the null when studies with a moderate to high risk of bias were included. Associations between vasectomy and high-grade prostate cancer (6 studies; adjusted rate ratio, 1.03; 95% CI, 0.89-1.21; P = .67; I2 = 55%), advanced prostate cancer (6 studies; adjusted rate ratio, 1.08; 95% CI, 0.98-1.20; P = .11; I2 = 18%), and fatal prostate cancer (5 studies; adjusted rate ratio, 1.02; 95% CI, 0.92-1.14; P = .68; I2 = 26%) were not significant (all cohort studies). Based on these data, a 0.6% (95% CI, 0.3%-1.2%) absolute increase in lifetime risk of prostate cancer associated with vasectomy and a population-attributable fraction of 0.5% (95% CI, 0.2%-0.9%) were calculated.Conclusions and relevanceThis review found no association between vasectomy and high-grade, advanced-stage, or fatal prostate cancer. There was a weak association between vasectomy and any prostate cancer that was closer to the null with increasingly robust study design. This association is unlikely to be causal and should not preclude the use of vasectomy as a long-term contraceptive option.

Dataset Information

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

Publications

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

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