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August, 1998
Selenium and "Man's Best Friend": Warriors Against Prostate Cancer
As the incidence of prostate cancer increases, so do the number of homeopathic and complementary treatments which promise a "cure" for the disease or its side-effects. many are pure promotional hype, unsubstantiated science or anecdotal claims without supporting data all geared to separate you from your money in return for a glimmer of hope.
Yet we know that certain vitamins and minerals, herbs and foods CAN have a positive therapeutic effect. This month we will look at one of them -- Selenium.
Dr. David Waters, Associate Professor of Surgery and Comparative Oncology, in the School of Veterinary Medicine at Purdue University has done significant groundbreaking research on the positive impact of selenium in prostate cancer chemoprevention utilizing several canine models.
Dr. Waters, please solve the confusion for me and I'm sure our viewers, how does veterinary medicine and the use of dogs relate to human prostate cancer?
DW: The dog is the only non-human creature in which prostate cancer naturally occurs with a high degree of frequency. Overall, cancer is the primary cause of death in 40% of dogs. In our work we have seen dogs manifest many of the same cancers as humans, i.e. breast, lymphoma, melanoma, prostate, etc.; thus we concluded that a critical hypothesis could be developed that would attempt to identify prostate cancer markers in dogs that would have relevance for chemoprevention potential for humans.
VS: How do dogs develop prostate cancer and are there tests, like the PSA blood screen, which provide a marker for canines and possibly humans?
DW: Just as with humans, we don't know why dogs develop prostate cancer and the PSA is not a valid test because the production of PSA is restricted to humans and non-human primates. Again, as with humans, there has not been a lot of attention paid to prostate cancer in dogs. We have begun the first systematic study of the disease because our preliminary research has shown that 55% of the dogs autopsied at time of death had prostatic intraepithelial neoplasia (PIN), which is the putative pre-cursor of many human prostate cancers, even though there had been no clinical signs of prostatic disease.
VS: Is this marker - PIN - significant?
DW: Definitely, because it tells us that early carcinogenic events may be occurring within the dog's prostate, but the animals aren't living long enough for the cancer to be identified or treated as such. If we can identify the elements associated with this marker we can conceivably develop a chemopreventive strategy viable for the treatment of prostate cancer in humans. In addition to PIN, we will be looking for correlation between other bio-markers, such as the level of selenium in dog toenails and the presence 8OHdG in the urine with the incidence of prostate cancer.
VS: You've recently been funded by the Department of Defense for a research proposal on the prevention of prostate cancer. Tell us about it.
DW: We are looking to validate the dog as a pre-clinical model for the testing of chemopreventive agents for prostate cancer. We are using dogs because, compared with rodents, they will present results more directly translatable to humans. We envision a short term study lasting approximately 2 years compared with 8 or more years using conventional protocols in human trials because the pet dog, in its diet and environment and breeding, more closely approximates the conditions under which human males will present prostate cancer. Dogs live in homes and locales as humans, approximately 30% of their diet comes from table scraps, they are not as in-bred as rodents and the ability to monitor their diet, etc. is easier to manage than with humans.
VS: Selenium, as a mineral supplement, has traditionally been used as an aid to preventing heart disease as well as an antioxidant enzyme. What is the benefit relative to prostate cancer?
DW: Our interest in Selenium and prostate cancer chemoprevention is based on our work which we did with Dr. David Bostwick(at the Mayo Clinic) and the data from Dr. Larry Clark (University of Arizona) that Selenium lowered the overall incidence of certain cancers, including prostate. It seems logical that we should determine the effect of selenium supplements on prostate carcinoma in a controlled investigation. We believe that selenium can have antioxidant properties which will reduce cumulative oxidant damage within the prostate. Significant benefits could be achieved by preventing or slowing the growth of the disease, since aging is the most significant risk factor.
VS: In your initial research, at what dosage levels will you evaluate for chemopreventive results?
DW: Our initial dosage in the dog models will be 3mcg and 6mcg per kilo of body weight which translates roughly into the daily recommendations of 200 mcg or 400 mcg in the human studies underway.
VS: At this point has there been enough evidence to recommend the usage of selenium in humans as a therapy against prostate cancer, or as a preventive measure against contraction of the disease?
DW: Our studies are only in the preliminary stage. We will receive funding from the Department of Defense in October '98 at which time we will begin to implement our research protocols. We are at least 2 years away from being able to definitely state that it is an effective chemopreventive agent.
VS: We have noted that some other "natural" substances such as, Vitamins C, D, and E and soy, calcium, magnesium and zinc are prostate cancer fighters. Can you comment on how Selenium interacts with these or other substances either positively or negatively?
DW: As part of our study we will also be testing DHEA. There is some concern that it may actually aggravate prostate cancer because of its pro-androgenic properties. But this is the strength of our experimental design; we will be running a double-blind trial using a placebo and controlled selenium dosages. We will be able to determine the efficacy of selenium in preventing/controlling the growth of pre-malignant lesions and prostate cancer in our subjects. Compare this with humans in a clinical trial who are being evaluated for a particular therapy, yet may be "contaminating" the results based on their taking some other self-medicated substances, thereby potentially altering or invalidating the data. Ultimately we anticipate that selenium may be used in combination with some other chemopreventive agent in a "cocktail" supplement.
VS: As with most clinical trials I would assume that you need subjects to help validate your hypotheses. What kind of canine volunteers are you looking for?
DW: We are looking for 360 healthy, sexually intact adult male dogs of various breeds. We have constructed an algorithm which factors in age and body size to produce an expected life span which would equate to a human life span. The dogs that will be in the study would equate to a human age range of 50 to 70 years. Although we would expect to pull most of our subjects from the Chicago Metro/Indiana area, we are seeking to create collaborations with veterinarians and pet owners around the country so that we can more effectively accrue cases.
VS: Will the dogs be exposed to any prostate cancer cells/tissue, viruses or any other potentially toxic agents?
DW: Absolutely not!!! They will receive either a sugar pill or selenium capsule daily for the rest of their lives, which we would estimate would be in the 2 year cycle of our study. They will also receive regular checkups to monitor their diet and overall health.
VS: After the dogs die of whatever natural causes, what will your procedure be?
DW: We will conduct an autopsy and evaluate the total prostate which will yield more data about the disease versus just a biopsy. We will also measure 8OHdG and toenail selenium levels to test our hypothesis in identifying markers viable for human prostate cancer.
VS: If our viewers wish to get more information on the study, how can they contact you?
DW: They should contact me via e-mail at: waters@vet.purdue.edu
VS: How can our viewers volunteer their dogs to be = participants in this trial? What is the criteria for acceptance and are there any stipends provided for participation?
DW: Dog owners can contact me directly or, better yet, through their local veterinarians as soon as possible and definitely prior to October 1st. The algorithmic-adjusted age of the dog will be the primary factor assuming that they meet the other criteria of health and sexual condition.
We will not be offering any stipend because of the limits of our study funding. However, prostate cancer touches the lives of over 200,000 men annually and a multiple number of family members and friends. There are millions of people who have seen the devastating impact of prostate cancer on their lives. We would sincerely hope that they would see this as a chance to stem the carnage of this disease on any other family by volunteering their animals to be a part of this effort. We only need 360 dogs out of the entire U.S. population!!!!
Thank you again, Dr. Waters, for sharing this exciting information and also providing us with some tangible evidence of the Department of Defense's Prostate Cancer Research support initiatives.
NOTE: We strongly urge our viewers to contact their Congressmen and Senators to push for more Federal dollars for prostate cancer research.
For additional information on selenium and prostate cancer, we recommend that you review Dr. Larry Clark's study. Click Here to see the article.
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