Genetics and inherited prostate cancer risk

Prostate Cancer: Major Genetic Risk Factor Found: “Harvard Medical School researchers have identified a DNA segment on chromosome 8 that is a major risk factor for prostate cancer, especially in African American men. The paper appears in the August electronic edition of the Proceedings of the National Academy of Sciences (also see PNAS’s
news tip below).

‘This paper identifies a genetic risk factor that about
doubles the likelihood of prostate cancer in younger African American
men,’ says principal investigator David Reich, PhD, Harvard Medical School
assistant professor of genetics with the HMS Department of Genetics and
the Broad Institute. ‘This finding may explain why younger African
Americans have an increased risk for prostate cancer than do other
populations–and may also explain why this increased risk in African
Americans attenuates with older age.'”

Source:
Medical
News Today


I came across this article today on the internet.

This reminded me about a recent discussion that I was having with one of my patients and then with a partner of mine.

Suppose you have a patient that has a strong family history of prostate cancer and a high PSA who has a biopsy. Lets also suppose that the biopsy does not show any evidence of definite prostate cancer, but has premalignant findings.

The patient asked me if I could take out his prostate. My answer was no, in that the side effects of the surgery were significant and that I did not feel any urologic oncologist would feel comfortable doing that.

Some statistics that are relevant include:
A mans lifetime risk of developing prostate cancer is about 1 in 8.
If you have a first degree relative (father, brother, son) who has prostate cancer, then you have about a 2.5 times higher chance of developing prostate cancer.
If you have a 2 first degree relatives (father, brother, son) who has prostate cancer, then you have about a 5 times higher chance of developing prostate cancer.
If your relative is under 65 years at the time of diagnosis, this gives you a higher risk.
If your brother has prostate cancer that is worse than if your dad has it.
Studies show than an identical twin has a 25% of having prostate cancer and a fraternal twin about 7%.

In the last few months, as I have performed more robotic prostatectomies and noticed more patients regaining sexual function and urinary function sooner, I am starting to reconsider my original answer.

One of my colleagues pointed out to me that women sometimes have mastectomies (removal of breasts) to prevent breast cancer if they are at a high risk genetically or have pre-malignant changes.

I wonder what peoples thoughts are on this. I wonder if other urologists had considered this or have done this.

I think my answer would still be to follow the patient closely and do frequent biopsies, but one day I think my answer will change. If there was a genetic test that concluded the patient had a 100% chance of developing prostate cancer that would change my answer to prophylactic prostatectomy.
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For urologists that subcribe to Contemporary Urology, there was a nice CME article where some of the above facts can be found that gave a nice review of genetic risk factors for prostate cancer.

9 thoughts on “Genetics and inherited prostate cancer risk

  1. Robert P. Caruso, M.D.

    While genetics is a definite risk factor (RF), it’s not an absolute factor in acquiring cancer. RF’s can be modified with diet, medications, etc. Cancer should also not be thought of as a one-way train. There are cellular reparative processes that can undo damage previously done. There are also immunologic checks and balances that under the right conditions can destroy a cancer that the cell itself can’t repair. The standard of care for the patient mentioned above would be rebiopsy in 3-4 months. I would also attempt to modify his risk with dietary supplements such as Theralogix 2.2, and with medications such as Avodart. Also, since Atypia can be a reactive process, you may want to consider a trial of at least a two week course of antibiotics and recheck his PSA. Even if this patient is destined to have prostate cancer, you likely have at least another 10-20 years of time where it would be organ-confined. While breast cancer has been treated prophylactically with mastectomy it doesn’t have the potential side effects of incontinence and impotence. You may be able to spare this patient decades of altered quality of life. Genetics testing may one day get to the point where we can better stratify risk and determine who should be offered prophylactic prostatectomy, but we’re not there yet.

  2. Mike Frank

    I have a family history of prostate cancer, and was in the highest risk category. What a surprise, at 51, I was diagnosed with pCa.
    Prophylactic removal makes perfect sense to me, although I’d be more comfortable if clear genetic markers could be identified.
    As for rapid recovery of continence and urinary function, I have to say that my DVP was all that I could have hoped for. However, while everything functions, I’d be a liar to say that I’d lost nothing in the process. The impact of surgery would always be a serious consideration, even with complete nerve sparing.

  3. Stephen Beck, MD

    I would not take out his prostate without evidence of cancer on the biopsy. I would just follow PSA and if it rises the repeat biopsy, he may be at high risk but that does not mean he has or will develop cancer.

  4. Marc Greenstein

    Tough question! Real tough. Personally, I would not perform a prophylactic prostatectomy on this gentleman. By watching him closely, his chances of having metstatic disease or biochemical failure is lower then the male with a higher PSA and a palpable nodule. At some point, his cancer will be discovered. Dr. Caruso commented about the side effects from surgery: with robotics and his young age he will most likely be 100% dry and have good erections after any robotic prostatectomy. This particular patient is probably worried about survival and not worried about side effects. Breast surgeons perform prophylactic mastectomies and I bet we’ll start seeing this practice in urology in about 10 years.

  5. Frank Petruno

    Hi, Great article, I’ve recently been faced with the following, psa of 4.7
    three months ago, a follow up 8 weeks later with a psa of 4.0 and then now 8 weeks later a psa of 4.3.
    I had a digtal that shows a normal prostate according to the urologist.
    I’ve scheduled a biopsy after the holidays. The reason for my blood work in the first place was a fluke. If I just had a physical the doctor would have felt a normal prostate for a man of my age (just turned 48 active and healthy) What do you suggest?

  6. Domenico Savatta, MD

    Urologists have different views on when to biopsy patients. I think most would agree that a PSA of 2.5 at a young age (50) would trigger a prostate biopsy.
    There is some new data from John Hopkins that concludes that it may be better to have a baseline PSA at age 40 and then every 1 to 5 years depending on the value. The rise in PSA (PSA velocity) is probably more important than the actual value.
    The story I use most is from a patient of mine who was 43 and had his wife who worked in a lab draw a PSA for no good reason. His PSA was mildly elevated for his age, he had a biopsy, which showed prostate cancer. He found me in second opinion for robotic surgery and had a surprisingly high volume of cancer in his prostate, but it was all contained with negative margins.
    Fortunately he had normal urination and sexual function within 3 weeks of his surgery and has a high chance of cure.

  7. Ben Batchelor

    Finally a forum to discuss this topic. I am 32 and my father was diagnosed with advanced prostate cancer at 59. His PSA went from less than 2.5 to 450 in less than 18 months. His father died from prostate cancer at 76. I am currently getting my PSA checked yearly and would stongly like to talk to any urologist that has an open mind to consider a prophylactic prostatectomy. I hope I would consider this in 8-10 years instead of now, but I would have no problem having this surgery. This is esp true after watching a perfectly healthy man be devastated by such an aggressive form of cancer.

  8. Domenico Savatta, M.D.

    1 year later and having passed 350 robotic prostatectomies I am changing my opinion on this. I have peformed many surgeries on young men and the results are extremely positive.
    I saw a young man today who had surgery 3 1/2 weeks ago. his recovery included a 24 hour hospital stay, a foley catheter in place for 3 days, no incontinence, 2 weeks off of work, and he is pretty sure he can have intercourse when he goes home to try.
    I would guess that a 40 year old man will likely have the following experience:

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