Impact of Vasectomy on the Development and Progression of PCa: Preclinical Evidence

[pjoshea13]

New study below [1].

A post on the possible influence of vasectomy on PCa development might seem like navel gazing at this point, but the subject continues to interest me.

When the first "bad news" about vasectomy was published long ago, the reaction was unexpected. Rather than warn men about to be snipped that there might be a PCa risk, the response was that the study results could not be correct because it was unthinkable that men throughout the world would reject the vasectomy option. There was seemingly more concern over the implications for women rather than men.

There are now enough studies that one could cherry-pick based on one's gut view, but the new study provides a plausible explanation for risk.

The team used "mice that underwent vasectomy vs. sham surgery". Very clever - the mice never knew which arm they were in. LOL. A molecule that was up-regulated in vasectomized mice was ZKSCAN3 [Zinc finger protein with KRAB and SCAN domains 3].

There was also "... 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 ... as an independent prognosticator, or vasectomy ... was associated with the risk of tumor recurrence."

The authors have an unusual rats nest of affiliations - two have 5.

My vasectomy was 42 years ago (26 years before diagnosis.) Did it increase my risk? Possibly, but it's of academic interest at this point. So many risk factors on the long road to diagnosis.

-Patrick

[1] pubmed.ncbi.nlm.nih.gov/328...

Cancers (Basel)

. 2020 Aug 15;12(8):E2295. doi: 10.3390/cancers12082295.

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

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 collapse

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.

[PhilipSZacarias]

Academic but interesting nevertheless.

[j-o-h-n]

Blank Bullets - Happy Vasectomy Day....

Good Luck, Good Health and Good Humor.

j-o-h-n Tuesday 08/25/2020 12:33 PM DST

[vforvendetta]

Thank you for your insight and for sharing.

[noahware]

It would seem to me that anything that might have an impact on the intraprostatic hormonal milieu might have an impact on PC development and progression. What is the impact of vasectomy on the intraprostatic hormonal milieu, for different subgroups of men? I wonder if we have much to go on there.

[Gearhead]

Thanks. Your introduction/summary is excellent.

[treedown]

I had work done in my nether regions as an infant and basically I ended up with a Vasectomy for my whole life and yadda yadda I am a proud member of this forum.

[Graham49]

Patrick

I suppose the most pertinent question for people like us would be : after a certain age would it be worth considering a vasectomy reversal? I don't think any of the studies so far get near answering this question?

[Blackpatch in reply to Graham49]

Interesting question... I had a vasectomy in my early 30’s that was successfully reversed in my early 40’s... and PCa still showed up in my early 60’s....

The mouse paper is interesting (did they really do fake surgery on mice? To what end??) but hasn’t turned up sufficient smoking gun evidence to cause much concern, I think...

Stuart

[bw1963]

Thank you for the information. I have wondered the same. I got a vasectomy at 40 and diagnosed with PCa at 55 and no family history of PCa.

[Burnett1948 in reply to bw1963]

Burnett1948. I had a vasectomy at age 42 then PCa at age 57.

[Rocketman1960]

I also always wondered if a vasectomy at 30 played a role in PC Gleason 8 at 50. It’s not to hard to imagine as the elevation of T in the body post vasectomy HAS to have an effect. I have warned my two sons to never get their nuts clipped. BTW, docs always warned of more sensitive testicles after a vasectomy. Yes this is the equivalent of having blue balls the rest of your life with no means to relieve.

[surfer07]

I too wonder if having a vasectomy caused my GL9 Pca with no family history of Pca . I was the health nut in the family , vegetarian , fit athelete etc..... . I had my vasectomy at 48 and Pca at 57 . A few months after vasectomy my wife read about these studies and I panicked . I rushed to the doctor to have my PSA checked and DRE in 2009 . I had a PSA of 1.4 and DRE was fine .Doctor told me not to worry . Checked my PSA every year .By 2013 PSA rose to 2.69. Doctor told me I was fine. No indication that I should be worried. I thought I was fine and stopped checking PSA.Had my PSA checked again 2018 at 57 and my PSA was 9.3 . Then MRI , biopsy confirmed Pca. It seems to me that the majority of respondents to this post have had a vasectomy. I have wondered all this time if we did a survey how many of us have had a vasectomy. Just wondering if there is smoke is there fire ?

[pjoshea13 in reply to surfer07]

Smoke & fire?

Those on the outside who seek to explain away an association often resort to the over-detection attack. Men who have vasectomies may be more inclined to be screened for PCa. As though men who have vasectomies take more care of themelves & that includes screening.

There is an association between PCa & thyroid cancer. A man with one is at a higher risk for the other. But since there is no biological explanation, the cause must be down to the behaviour of the man. Blame the victim and overscreening.

So, I'm thinking maybe someone has looked for a connection between vasectomy & thyroid cancer? LOL

Not mentioned in the PCa studies is the fate of sperm, that young men, at least, continue to produce in copious amounts. What happens to it after vasectomy? The body creates antibodies for spermatazoa. But are other anti-self antibodies produced?

From 1988:

"The possibility of autoantibodies--other than sperm antibodies--developing as a consequence of vasectomy has been investigated in 255 volunteers. During the first year after vasectomy no obvious increase was observed in the occurrence of any of these antibodies (rheumatoid factor, antinuclear antibodies and antibodies against smooth muscle, mitochondria, gastric parietal cell, thyroid microsomes and thyroglobulin). Ninety-nine of the patients were also examined for agglutinating and immunofluorescent antibodies to sperm to see if there was any relationship between the occurrence of anti-sperm antibodies and other autoantibodies. However, the prevalence of non-sperm autoantibodies did not differ in two nearly equal groups of patients with and without indications of autoimmune reactions to spermatozoa, respectively. Consequently the present results lend no support to the hypothesis that vasectomy could induce autoimmunity to other autoantigens than sperm-specific antigens." [1]

But they looked! There was concern.

Back in 1977 we have:

"Effect of vasectomy on thyroid function" [2]

"Long-Evans rats vasectomized unilaterally or bilaterally at 2 months of age showed marked reductions in weight of testes, seminal vesicles and prostate glands 2 and 12 months post-vasectomy. Thyroid weight, thyroid 131I uptake, serum PB131I, circulating levels of serum T4 and chromatographic analysis of thyroid hydrolysates revealed no alterations due to vasectomy. These findings indicate that vasectomy, unilateral or bilateral, and whether of 2 or 12 months duration, did not exert an effect on thyroid function."

I had my vasectomy in 1978 & was unaware that this research was going on.

It's fun to scratch around in the archives for associations.

***

Length of marriage is a PCa risk. Seems crazy. No history of numerous partners. No history of STDs. A blameless life. But for vasectomized married men, plenty of unprotected sex. Perhaps not as innocent as I thought at the time?

-Patrick

[1] pubmed.ncbi.nlm.nih.gov/20409/

[2] pubmed.ncbi.nlm.nih.gov/569...