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Old 08-03-2009, 05:05 PM   #1
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Exclamation Selenium for prostate cancer - growing more complicated

On August 1, Mart16 (Martha) pointed out just published research suggesting that consumption of selenium for prostate cancer could be a bad or very good idea depending on our genes. Great thanks again to Martha for highlighting this important development!

Specifically, depending on whether we had the AA versus some other (VV, VA) version of the gene for MnSOD, selenium looked like it would be very helpful or perhaps somewhat harmful. (You can see her post and my response as responses #5 and #6 on the recent Statistics thread. I thought this important news deserved its own thread.)

Background (in blue, so anyone who just want the bottom line can skip this section of a fairly long post)

This is important news, because, up until now, the bulk of news on selenium indicated that it helped lower the likelihood or risks of prostate cancer and was very likely safe in the relatively low dose of 200 mcg (micrograms) per day. In fact, the exciting results of the Nutritional Prevention of Cancer trial (Dr. Larry Clark), published in 1996, indicated that daily consumption of 200 mcg of selenium lowered the likelihood of getting prostate cancer by nearly two thirds (64%)! However, that trial was relatively small, had some holes in documentation of prostate cancer diagnoses and outcomes, and was directed mainly at skin cancer, with data on selenium and other cancers being a side benefit, a fact that somewhat lowered the level of confidence that the results were a good match to reality.

Information in that trial and in other research suggested a tantalizing substantial benefit, but one that too often seemed to elude the grasp of patients. Research also indicated that selenium worked even more effectively when it was combined with vitamin E. Then the massive SELECT trial (selenium, Vitamin E, combination, and placebo) blew up about a year ago, with no support for the effectiveness of selenium, though it appeared that, by a bad twist of fortune, a poor choice of the trial version of selenium had been made. (There are several forms, and they act quite differently.) Also, research published shortly before the SELECT trial was launched, and then bolstered with additional research after trial launch, indicated that it was not the popular alpha tocopherol form of vitamin E that was helpful, but rather the gamma and perhaps delta forms.

(I think the coup de gras for the SELECT trial came when the research team realized that the dose selected for vitamin E - 400 IU - would create a high bleeding risk in a small percentage of trial participants, a risk that would have been avoided if only the dose had been set at 200 IU. Again, unfortunately, the original dose of 400 IU was considered quite safe at the time the trial was launched; subsequent research showed that it was not so safe.) (There is a bright side to this information: it shows how strictly the ethics and patient safety side of trials is enforced, which is very important to those of us who enter trials! )

Also, reexamination of data from the earlier Clark trial indicated that there might be a very small but real increase in the risk of diabetes or insulin resistance due to selenium supplementation, a risk strong enough that Dr. Charles "Snuffy" Myers, MD, one of the world's top experts on nutrition and prostate cancer, advised men who had diabetes or insulin resistance to discuss testing for their selenium levels with their doctors and to "consider stopping selenium until this issue is clarified." (from the Vol. 10, #4 Prostate Forum, "Nutrition Revisited, Part II," copyright date November 2007)


The Recent Research (senior author Phillip Kantoff, MD)

Dr. Philip Kantoff, MD, director of genitourinary oncology at the prestigious Dana-Farber Cancer Institute in Boston and colleagues at the University of California, San Francisco (another institution that is prominent in prostate cancer research and innovative practice), appear to have taken a huge step in understanding how selenium relates to prostate cancer: it looks like our individual genetic makeup regarding the gene for MnSOD - manganese superoxide dismutase is the key to whether selenium is beneficial. (One problem up front: it is a virtual certainty that almost no prostate cancer patients know whether they have the beneficial or the possibly harmful form of the gene - I certainly don't, and I've been taking selenium for more than nine years now! )

Here's the formal citation of the research paper:

Plasma selenium, manganese superoxide dismutase, and intermediate- or high-risk prostate cancer. Chan JM, Oh WK, Xie W, Regan MM, Stampfer MJ, King IB, Abe M, Kantoff PW. J Clin Oncol. 2009 Aug 1;27(22):3577-83. Epub 2009 Jun 15.

To keep this first post from getting even longer, I'll just say that those with the AA version of the gene appear to get a big benefit from selenium, while there appears to be the potential for somehat riskier prostate cancer if we have the VV or VA versions of the gene. Dr. Kantoff had been looking at the relationship of MnSOD and selenium for a number of years, and his team's earlier information was all on the good side, though with the AA version clearly outshining results for VV and VA patients. That changed with the recent paper, which showed increased risks for VV and VA men who consumed a lot of selenium. It's clear that Dr. Kantoff was also concerned that most of the men in the just published study - 75% - had one of the forms of the gene that were on the risky side. (I have seen just the abstract of the key recent study, and it was not clear to me whether the men in that study represented the general population or a special group; that could affect the distribution of gene forms.)

At this point, I've looked at abstracts of three papers Dr. Kantoff has authored or co-authored on this subject. You can see them if you go to www.pubmed.gov, a site we can use on this board because it is Government sponsored, and search for (without the quotation marks) " kantoff p [au] AND prostate cancer AND selenium ". Two earlier papers are available in full using the free links on PubMed. I've read both, and one is just a summary of the other, which is a detailed study. There's enough there to convince me that this is an important development.

One of the first thing the team hopes to do is to go back to the SELECT trial blood samples to see if they can get a clearer picture of benefit and risk depending on the MnSOD gene versions. To me that looks like a fairly low cost but high payoff step, and I hope they are able to do it shortly.

That's enough from me on this for tonight.

Thanks again to Martha!

Jim

 
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Old 08-03-2009, 07:13 PM   #2
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Re: Selenium for prostate cancer - growing more complicated

Whoa...I read through this twice, and I'm not sure I grasped it all. This seems like one of the steps in progression of medicine, but hard to see just how far it will lead.

I recall talking with one of my doctors about my (now 17-year old) son needing to start getting PSA tests by the age of 35 or 40 (start early, since PC is in the family), but then he paused, and said reflectively, almost to himself, something like, "But by that time they will be doing much more refined testing by analyzing the individual's genes."

Maybe we're seeing into that future now.

tks for the info,
kcon

Last edited by kcon; 08-03-2009 at 07:14 PM.

 
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