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Hereditary Prostate Cancer and How to Lower Your Risk

Assistant Professor of Urology Dr. Michael Whalen discusses prostate cancer, specifically hereditary prostate cancer and dietary changes to lower one's risk of developing this type of cancer.
Hereditary Prostate Cancer and How to Lower Your Risk
Featuring:
Michael J. Whalen, MD
Michael J. Whalen, MD is Assistant Professor of Urology at the George Washington University School of Medicine & Health Science.  He graduated magna cum laude with a B.A. in Neurobiology from Harvard College and received his medical degree from Columbia College of Physicians & Surgeons in New York City.  He completed his residency in Urology at New York Presbyterian Hospital-Columbia University Medical Center. 

Learn more about Michael J. Whalen, MD
Transcription:

Dr. Michael Smith (Host): A small percentage of prostate cancers can cluster in families. These are hereditary cancers and they are associated with gene mutations that can be inherited and they tend to develop earlier in life. Welcome to the GW Medical Faculty Associates Podcast. I’m Dr. Mike Smith, and today’s topic, Hereditary Prostate Cancer, and how to lower your risk. My guest is Dr. Michael Whalen. Dr. Whalen is assistant professor of Urology and Urologic Oncology. Dr. Whalen, welcome to the show.

Dr. Michael Whalen (Guest): Thanks very much for having me.

Host: So how about giving us a nice overview of prostate cancer, you know and specifically focusing on – I guess what are the two broad categories, sporadic versus hereditary?

Dr. Whalen: Sure, so prostate cancer has been known to occur in men who have a family history, that is if their father or brother or grandfather or uncle for example has had the disease. African American men are slightly higher risk as well, and because of the family incidents of this disease, it’s been suspected for many years that there is a hereditary component to it and possible gene mutation that might occur in one generation that can be passed to the next generation. There’s been gene linkage studies that hadn’t been so fruitful in the past, but through recent developments in a very large nationwide program called the cancer genome atlas, it’s now been discovered that there are certain mutations that occur in prostate cancer that can be inherited in families. So we think of prostate cancer as being either hereditary, meaning having been inherited from one’s father, or sporadic meaning developing what we’d say is de novo or newly in a generation in a family that hasn’t had prior instance of prostate cancer. So some of these gene mutations are something called HOXB13, which has been found in men of norther European decent and there’s also work being done that has identified genes usually involved in the repair of damaged DNA called homologous recombination repair, and these genes are important for other cancers, and maybe popularly associated with breast cancer. So these are the BRCA-1 and BRCA-2 genes that people think of as being associated with breast cancer and have come under a lot of scrutiny, especially for women who are carriers for these genes and having prophylactic mastectomies, like Angela Jolie, so BRCA-1 and 2 have also been shown to be important in prostate cancer, and it’s true that men who have a history of prostate cancer in their family are at high risk, but also men who have a history of breast cancer or even ovarian cancer in their family may be at higher risk for developing prostate cancer, and that’s because of this new understanding of the association of BRCA-1 and 2. BRCA-2 tends to be a little more threatening with the incidence of prostate cancer being about nine times the rate of the average population and BRCA-1 being about two times the rate of the general population.

Host: And so just to kind of wrap that up a little bit, so we’re talking about mutations and genes that can be passed down that seem to be involved in DNA repair and those genes are passed down and some of those genes are associated with a pretty high risk of developing prostate cancer. So hearing that kind of information, I want to know if there is prostate cancer in my family, should I get tested? Is there genetic testing for this to identify some of those genes?

Dr. Whalen: Oh absolutely so the basic screening recommendations for prostate cancer, for the average population, that is for not having a risk of prostate cancer or any incidence of prostate cancer in the family, is to have a PSA blood test drawn starting at age 55 and also a digital rectal exam to assess the contour and shape of the prostate and make sure that it feels normal. For men who have a family history or slightly higher risk because of race such as African American men, the recommendation for starting screening according to the American Cancer Society is at age 40 so it’s considerably less. Similarly if there is a known family history of any of these mutations such as BRCA-1 or BRCA-2, the recommendation is to start screening earlier at age 40. Now there are ongoing studies in Europe, something called the impact study, which is looking at whether carriers of BRCA-1 and BRCA-2 have a higher – not only a higher incidence of prostate cancer but whether these prostate cancers tend to be more aggressive. Now the data is still premature, we don’t have outcomes from that, but as the data matures, we’ll have a better understanding. I will say that preliminarily, although the incidence of prostate cancer was similar in the normal gene group versus the BRCA-1 and 2 mutated group, the aggressiveness of the prostate cancers diagnosed in the BRCA-1 and 2 group was actually higher, so not only is there the chance for more men carrying the BRCA-1 and 2 to be affected by prostate cancer but it also may be more aggressively. Now there is commercially available genetic testing and we have the facility to do that at GW through the supervision of a genetic counselor. Men who should consider being tested genetically, which is different than prostate cancer screening, are men who have three different generations affected, any man diagnosed with metastatic prostate cancer, and any man who was diagnosed with prostate cancer who has a family history of breast and ovarian cancer in two first degree relatives, anyone in the family diagnosed as a first degree relative before the age of 65, or a prostate cancer that is more – basically more aggressive or Gleason 8 to 10. Now insurance companies will cover the testing if certain criteria are fulfilled, mostly having a large number of people in the family who have the disease. So again, the genetic testing usually is reserved for men who have already been diagnosed, and that’s different than screening, consisting of the blood test and the rectal exam. So we don’t usually offer genetic testing to men who have not been diagnosed, except for in that scenario when they may have a known genetic mutation such as BRCA-1 and BRCA-2.

Host: So, hearing all this, a couple of things I want to cover real quick. So on one hand, you mentioned that if there is that family history, if there is an indication that there could be some of these mutated genes being passed down, and they might be associated with some aggressive prostate cancer, the key thing though is still to get your screening, if need be the genetic testing because is it true that even if you do develop that cancer, early diagnosis and early treatment still has good outcome?

Dr. Whalen: Absolutely, so early diagnosis is critical. I mean with the advent of PSA, there’s an advantage of about six to eight years with detecting the disease earlier than if we didn’t have that PSA blood testing. PSA has come under criticism and is controversial but it now is endorsed by the US Preventative Services Taskforce as a grade C recommendation, meaning that a patient should discuss the risks and benefits of screening with their clinical provider – with their doctor. So prostate cancer is the most common non-skin malignancy in men, it’s the second leading cause of cancer deaths in the US, but it’s not only treatable when detected at an early stage, but also curable. So getting screened and for those men at risk, having the genetic testing can set people up for success with treatment if God forbid they are diagnosed.

Host: Right, right. I wanted to ask you something. I want to take a little tangent here, a little side question because I’m sure we have listeners right now, Dr. Whalen, that probably have been diagnosed with prostate cancer, and you mentioned something, the Gleason, the Gleason score. Can you just explain that a little bit, and what that means, low number versus high number?

Dr. Whalen: Sure, so the Gleason score is basically interpretation of the architecture of the cells when looked at under the microscope, tissues obtained during a transrectal biopsy, and the tissue is put onto slides, it’s then looked at under a microscope. So the Gleason score gives us a criteria for essentially biologic aggressiveness of the cells and this is then validated and actually updated recently. So the prior scoring system used to go from 6 to 10, six being the lowest, ten being the highest and most aggressive, and we now use a Gleason grading group system from 1 to 5 to just facilitate and make more straightforward the grading scheme. So one Gleason grading group is the least aggressive and five is the highest, and the total score comes from adding the two most common architectures found under the microscope into a single score. So in the old system it used to be, a six was composed of 3+3, a seven could be composed of 3+4 or 4+3, and the 4+3 means that there’s more high grade disease than low grade disease and that final interpretation of the Gleason score contributes to the aggressiveness of the cancer and also helps the patient and the urologist understand what treatments are best for patients. These days some low Gleason score and therefore low risk prostate cancers can be watched for a period of time and may not need to be treated, that depends on also the patient’s age and what their other medical problems are. Prostate cancer sometimes can be a disease that a man sort of dies with rather than of, meaning it’s not likely to shorten their life expectancy because it’s so slow growing. So we understand that some prostate cancers can actually be watched, but those with higher Gleason scores often are best suited with treatment because of their potential to continue to grow and possibly spread if no intervention is undertaken.

Host: Gotcha. So let’s come back to what we’re really talking about here, and what I’d like to end with is, so we touched on a little bit of what prostate cancer is, the sporadic versus the hereditary and some of the screening and genetic testing that’s available, but just in general, Dr. Whalen, what can a man do to decrease his risk of developing prostate cancer?

Dr. Whalen: Exactly, and for those people who have family history or do carry one of the gene mutations, like BRCA-1 or BRCA-2, early detection is key as we mentioned, and whether or not the understanding of having these risk factors allows us to give medication to delay or prevent the onset of prostate cancer. It’s a little too soon for that. There have been some studies looking at the role of medications called finasteride or dutasteride, which are given for benign enlargement of the prostate associated with urinary symptoms, and also taken by men to prevent hair loss, so something like Propecia and these studies were not definitive and didn’t result in FDA approval of those medications for prevention of prostate cancer in men, so medications aren’t really on the table. But there has been a lot of work in dietary modification and nutritional changes as a way of mitigating one’s risk and there’s been several epidemiologic studies looking for associations with certain diets, and the incidence of prostate cancer. Now these are not randomized controlled studies and it’s hard to do that in a large population based way, but looking back in time we see that certain foods are associated with a higher incidence of prostate cancer, and although we can’t prove causality, there is an association there. So these dietary modifications often have the objective of engaging in a more Mediterranean style diet than the typical Western diet, and the added advantage of that is there can be improvement in cardiovascular health as well with reduction in cholesterol. So these changes involve cutting down on red meats and processed meats. Also avoiding foods high in saturated fat. Saturated fats and trans fats can come from fatty meats, also sweets and things like desserts and also using a lot of butter, trying to get fats from sources such as vegetable oil, or fish, or even nuts, and the other component that’s been studied is the influence of dairy and milk as a negative factor for increasing for risk of developing prostate cancer. So cutting out some of those things has been shown to be beneficial. As well, there’s certain foods that have been particularly targeted for being advantageous or beneficial in reducing risk of prostate cancer development, and those things consist of green tea, believe it or not, which has antioxidant properties and has been shown to reduce the growth rate of prostate cancer cell lines in vitro as well as reducing prostate cancer development in mice who have been genetically engineered to form prostate tumors, actually when you give them green tea, even though they’ve been genetically engineered to form the tumors, they actually grow less tumors, which is very exciting, and it’s been looked at in human studies, and may be beneficial for reducing preliminary conditions of the prostate, so green tea can be taken either as you would expect, with the bag steeped in hot water or with capsules, that can be purchased in a decaffeinated way from the health food store. Lycopene, which is a food found in red foods – I’m sorry which is an additive found in red foods such as tomatoes and tomato sauces as well as watermelon, pink grapefruit, apricots, carrots, and red cabbage, also have been shown to be beneficial in reducing prostate cancer cell growth and reducing something called KI67, which is proliferation index of prostate cancer cells. Soy products are very good because of their phytoestrogens, which can actually bind to the androgen receptor on prostate cancer cells and help to mitigate growth. Also for men who are taking androgen deprivation therapy for advanced prostate cancer, phytoestrogens found in soy products have been shown to reduce the incidence of hot flashes, which can be very bothersome for men being treated for advanced prostate cancer. A couple other things that are advantageous are flax seed, believe it or not, because of their lignins, which are phytoestrogens and have certain properties that combine to the androgen receptor, and so these foods have been shown to be very beneficial. The last one that I’ll mention is pomegranate which believe it or not has very potent antioxidant properties, and you hear about it in a cardiovascular way. It’s been studied that drinking a glass of pomegranate juice a day can reduce your risk of prostate cancer and can also reduce the risk of something called PSA doubling time for men who have been treated for prostate cancer, and now have a rising PSA possibly indicating disease recurrence, so the pomegranate juice has been shown to actually slow down that recurrence rate.

Host: Yeah, that’s a lot of great advice and suggestions and I think you make a good point, Dr. Whalen, that even though maybe we can’t – we don’t have a definitive answer about these dietary changes, but in large population studies, it’s been shown that they can be beneficial, and it makes sense right, that Mediterranean diet, better fats, more fruits, leafy greens, it’s really not that hard to think that this kind of diet will have a positive changes. Let’s just, you know to end for the audience, Dr. Whalen, just real quick in a summary form, what would you like my audience to know about prostate cancer?

Dr. Whalen: So with regards to dietary supplements, one thing it’s complimentary on alternative medicine. So it’s a way of approaching the treatment of the disease in parallels or even doing it to prevent the disease from forming. It’s important to mention the supplements to your doctor because some of them do have property that can alter the function of other medications such as vitamin K within green tea, so that can affect anticoagulant medication. Soy has a lot of oxalate, which can contribute to kidney stones, so that’s one thing, if you’re thinking about taking these supplements, which I definitely encourage, just make sure that your doctor is aware of them and not only your urologist but also your primary care doctor to make sure there’s not adverse interaction with other medications. In terms of prostate cancer, there’s a thrilling amount of developments that have been made in the realm of molecular biology and understanding of genetics, and as we accumulate knowledge of these gene mutations, we will also in parallel be developing focused medications to be able to treat these. Right now, it’s in the domain of advanced prostate cancer, but there’s every expectation that the therapies will filter their way down to more localized prostate cancer in our efforts to provide more up to date medical care in the realm of precision and personalized medicine. Prostate cancer detection early, portends a more favorable cure rate and prostate cancer definitely is curable so I encourage men who have a family history or who just are concerned about their health to talk to their primary care doctor about being screened, and the other thing that we talked about was the role of the BRCA-2 mutation and development of prostate cancer, so any man not only with a family history of prostate cancer but also breast or ovarian cancer should speak seriously with their doctor about being screened early.

Host: Dr. Whalen that was a great summary and I want to thank you for the work that you’re doing and thank you for coming on the show today. You’re listening to GW Medical Faculty Associates Podcast. For more information, go to gwdocs.com, that’s gwdocs.com. I’m Dr. Mike Smith, thanks for listening.