Is there a link between genetics, selenium, and prostate cancer risk?

A new article in Cancer Prevention Research not only suggests the possibility that there is a very real association between selenium levels in serum after all, but it also helps to explain why this association may not have shown up in the large, double-blind, and randomized SELECT trial.

Despite the evidence of the SELECT trial, which clearly showed that treating thousands of randomly selected men with selenium supplements did not decrease their risk for prostate cancer, there are still many researchers who are investigating the possibility of a role of selenium in prostate cancer risk.

Penney et al. have now carried out a sophisticated genetic analysis designed to identify common variations in single-nucleotide polymorphisms (SNPs) associated with genes that code for a selenium-containing protein called SEP 15 and for another gene that appears to affect the  efficiency of selenium incorporation into SEP 15. SEP 15 is a recently discovered protein which is highly expressed in the prostate. It has previously been suggested that this protein may play a role in the development and progression of prostate cancer, either independently or by modifying the effects of selenium itself.

The research group then looked for associations between the presence of absence of these genetic SNPs, prostate cancer risk, and prostate cancer-specific mortality, as well as their interactions with plasma selenium levels, in 1,286 prostate cancer patients and 1,267 matched controls enrolled in the Physicians’ Health Study — with the following results:

  • Overall, there was no statistically significant association between SEP 15 polymorphisms and prostate cancer risk.
  • Three of the SEP 15 SNPs were significantly associated with prostate cancer-specific mortality based on the idea that these SNPs are recessive genetic variants. (Recessive genetic variants are only actually expressed when you inherit the recessive gene from both of your parents. Red hair is a well-known example of physical expression of a recessive genetic variant. You won’t have red hair unless you inherit the right gene from both of your parents.)
  • One SNP significantly modified the association of plasma selenium with prostate cancer-specific survival.
  • High serum levels of selenium were associated with a reduced risk for prostate cancer-specific mortality only among those patients who did not have the increased risk genotype.

The authors conclude that there is some evidence that genetic variation in the expression of the SEP15 protein may influence prostate cancer mortality. They further conclude that the association between selenium and prostate cancer-specific mortality is modified by another gene variation, and that, as a consequence, some men with prostate cancer may benefit more from the amount of selenium in their bloodstream than others, depending on their genotype.

In the same issue of Cancer Prevention Research, Platz offers editorial comment on this research, noting the potential implication that, “Selenium may prevent poorer-prognosis prostate cancer and its progression …, but only in men with genetic backgrounds that influence the requirement for selenium.”

This study by Penney and colleagues is an excellent example of just how complex it may be to understand why some people respond significantly to small variations in things like selenium levels whereas the same variation may be irrelevant to others. Their study demonstrates that variations in at least four different genes appear to be affecting the expression of just one of the proteins that may be important to the development and progression of prostate cancer. But there are dozens of proteins and enzymes that affect the development and progression of prostate cancer, implying that the individual expression of perhaps hundreds of slightly different genes may be relevant to risk for and aggressiveness of prostate cancer in a specific individual.

It may take years more before we can even tell if the hypothesis proposed by Penney et al. is correct. If it is, then we may actually be able to lower the risk for prostate cancer in a specific subset of individuals, but things may still be more complex. Just giving selenium supplements may not be sufficient to stimulate the necessary biological and biochemical pathway leading to the “right” amount of SEP 15 in the prostates of the right patients at exactly the right time.

One Response

  1. Thanks to the InfoLink for highlighting this new paper. I was aware of a separate paper, also with Dr. Kantoff as senior author but with Harvard as the source institution rather than UCSF, that addressed different (I think) genetic aspects of selenium and prostate cancer risk that was published last year. It related to a variant of the manganese superoxide dismutase (SOD2) gene and selenium’s role in prostate cancer risk. There too, selenium level correlated inversely (a good thing) with risk very well for men with the “AA genotype”, whereas, for men with the “V allele”, there was a direct correlation: higher selenium was linked with higher risk!

    Can anyone confirm that these two studies involve separate genes, and not just aspects of the same gene? I’m thinking they are separate.

    This is really exciting stuff! If it pans out, we will be considerably further along the road toward personalized medicine, at least where selenium and prostate cancer are concerned; genetic tests will enable us to have a good handle on who should and who should not take selenium to help prevent and to help deal with prostate cancer!

    Some other points deserve mention. First, it is arguable that the form of selenium used in the SELECT trial was not a form that had shown promising activity against prostate cancer — an apparently unfortunate choice for the trial. Therefore, it is likely we don’t know that all selenium supplements won’t be effective; we only know that one form did not work in the kind of population studied in the trial.

    Another point is that even earlier trials suggested that supplementing with selenium did not seem to help much if men were not deficient in selenium — below average, at the outset.

    Of course, as patients we are faced with what to do about selenium as knowledge gradually advances. I’ve been taking it for 10 years now, starting within months of being diagnosed. I’m not sure, of course, if selenium is one of the reasons I’ve done quite well on intermittent triple hormonal blockade with finasteride maintenance plus bisphosphonate and lifestyle tactics support for my challenging case. But I think the odds are favorable that selenium is helping me cope with the disease. Because I have done well, I’m going to keep taking 200 mcg per day. I’m also going to stay closely tuned to research and information about pertinent genetic tests.

    Thanks again for pointing out this interesting new study!

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