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Does selenium prevent prostate cancer?
Someone is bound to ask you. (March 2003)
Should all men take 200 mcg selenium to prevent prostate
cancer? The answer is currently straightforward. No one knows. Otherwise
it would be unethical to conduct the SELECT Trial (Selenium and Vitamin E
Cancer Prevention Trial) which addresses this question by comparing the
outcome of men taking selenium 200 mcg, or Vitamin E 400 mg, or a
combination of the two or placebos. This study was commenced in July 2001
with a goal of recruiting 32,400 men. Dr. Gary Goodman at the Swedish
Hospital Cancer Institute is the local coordinator and information about
registration is available at 215-3245. Because of the long incubation
period preceding the clinical detection of PC the trial is scheduled to
run 12 years. Four other trials are also addressing intervention with
selenium 200 mcg/day: one for men with high PSAs and negative biopsies; a
three year SWOG study for men with HGPIN; a study to evaluate the cellular
effects of selenium administered for 6 to 8 weeks before prostatectomy;
and a "watchful waiting" study for older men with PC who choose to defer
definitive treatment. Collectively, these studies will provide guidance
for the future management, and men without established opinions on this
issue should be encouraged to participate. However, many men will feel
that "time is short and science is long" and choose to hedge their bets by
taking the 200 mcg. There is a strong body of epidemiological and
laboratory support for their choice.
Why selenium? Selenium is a non-metallic trace element found in alkaline
soil which enters the food chain via wheat, corn, forage crops, and nuts.
The current dietary recommendation is 20 - 40 mcg daily. This element and
subsequent metabolic products are combined with amino acids, i.e.
selenomethionine, and incorporated into many enzymes. Selenomethionine is
a necessary component of glutathione (mentioned above). Two early
nutritional studies focused interest on selenium's role in cancer
prevention. Yoshizawa (JNCI,Aug,1998)reported a "Study of prediagnostic
selenium level in toenails and the risk of advanced prostate cancer".
33,737 men submitted clippings; 181 cases of PC were diagnosed during the
study; and when compared to the lowest quintile values of selenium men in
the highest quintile had 65% fewer cancers. The second study was first
reported by Dr. Larry Clark in JAMA, Dec 1996 and updated July 2002. It
was based on the 1312 man Nutritional Cancer Prevention Study conducted
primarily to evaluated selenium's affect on skin cancer This study
compared 200 mcg/day selenium to a placebo. It was noted that 28 men
developed PC during the study: 13 who had taken selenium compared to 35 in
the placebo group.
What basic cellular mechanisms might explain selenium's postulated role in
PC prevention? Until recently selenium had been assigned two roles: as an
antioxidant and an inducer of apoptosis. Prostate cells are persistently
subjected to extensive risk of injury from the reactive oxygen free
radicals resulting from the metabolism of androgens. And selenium serves
as a major scavenger of these mutagenic agents. The glandwide risk
resulting from this adverse environment may, in fact, be the "field
effect" that underlies the very frequent multifocal distribution of PIN
and PC in the prostate gland. As an inducer of apoptosis (programmed cell
death) selenium contributes to the elimination of damaged, potentially
cancerous cells. In a 1998 study Clark found in tissue culture that
selenium caused greater growth inhibition to PC cells than normal cells.
The newest information on the cellular function of selenium comes from two
recent articles in the JNCI. In the January 2003 issue selenomethionine is
reported to initiate DNA repair, a process key to correcting adverse
cancer causing mutations. The data suggests that selenium activates the
p53 gene, a master regulatory enzyme that monitors quality control by
promoting DNA repair or, alternatively, induces apotosis in hopelessly
damaged cells. When activated, the gene turns on 100 or so other genes
that effect repair or apoptosis. Selenium increases this activity
threefold compared to control. There is a downside to this discovery,
however, since this scenario requires that p53 gene is fully functional,
i.e. non-mutated. Unfortunately, in possibly half of all cancers, p53 is
non-functional due to mutational injury. However, in PC this inactivation
of the p53 occurs late in the cancer process, allowing the hope that
selenium, when used early as chemoprevention, will find a functional p53
to work with. The final article (JNCI, February 2003),"Effects of Dietary
Selenium Supplementation on DNA Damage and Apoptosis in Canine Prostates",
brings the investigations closer to man ("dogs and humans,[are] the only
two species in which prostate cancer develops spontaneously with
appreciable frequency"). The dogs were treated for seven months before
their prostates were examined. The authors concluded: "dietary selenium
supplementation decreases DNA damage and increases epithelial cell
apoptosis within the aging canine prostate."
Bottom Line: What to do? Robert Frost alludes to our current situation:
"We dance round in a ring and suppose, but the secret sits in the middle
and knows." In time the clinical studies may reveal the secret.
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