Philip Kantoff, MD
Higher selenium levels in the blood may worsen prostate cancer
in some men who already have the disease, according to a study by
researchers at Dana-Farber Cancer Institute the University of
California, San Francisco.
A higher risk of more aggressive prostate cancer was seen in men with
a certain genetic variant found in about 75 percent of the prostate
cancer patients in the study. In those subjects, having a high level of
selenium in the blood was associated with a two-fold greater risk of
poorer outcomes than men with the lowest amounts of selenium.
By contrast, the 25 percent of men with a different variant of the
same gene and who had high selenium levels were at 40 percent lower
risk of aggressive disease. The variants are slightly different forms
of a gene that instructs cells to make manganese superoxide dismutase
(SOD2), an enzyme that protects the body against harmful oxygen
The research findings suggest that "if you already have prostate
cancer, it may be a bad thing to take selenium," says Philip Kantoff, MD, director of Dana-Farber's Lank Center for Genitourinary Oncology and
senior author of the study that is published by the Journal of Clinical Oncology
on its website now and later will be in a print journal. The lead
author is June Chan, ScD, of the University of California, San
The unexpected results are the first to raise concern about this
potentially harmful consequence of taking supplemental selenium. Kantoff
says, "These findings are interesting particularly in light of the
recent negative results from the SELECT prevention study, which asked if
selenium could protect against prostate cancer."
The new study reveals the strong interaction between selenium and
SOD2 to influence the biology of prostate cancer, a finding that these
investigators had shown in a previous study. The authors say the current
research demonstrated that variations in the make up of the SOD2 gene dramatically alter the effects of selenium on the risk of aggressive prostate cancer.
Selenium is a mineral found widely in rocks and dirt. Small amounts
of selenium are essential for health: 40 to 70 micrograms is the
recommended daily intake.
In recent years, supplemental selenium has been sold and promoted as a
means of preventing prostate cancer, largely based on observational
studies that found higher risk of prostate cancer incidence and
mortality in areas of the country that are naturally low in selenium.
However, research aimed at confirming the benefits of selenium supplementation have been mixed.
Recently, the SELECT study, which involved 35,000 men, was halted
early when, after more than five years, it showed that the supplements
didn't affect the incidence of prostate cancer.
Previous studies had found that the risk of developing prostate
cancer was modified by a strong interaction between SOD2 and selenium.
The new research was designed to look at the effect of this interaction
on men already diagnosed with prostate cancer.
Scientists examined banked blood samples, DNA, and medical records of
489 male Dana-Farber patients diagnosed between 1994 and 2001 with
localized or locally advanced prostate cancer. Their mean age was 62,
and their mean PSA (prostate-specific antigen) measurement was 6.0
About half the men were assessed as having a good disease risk,
one-third had an intermediate risk, and the remaining one-sixth were at
poor risk. The researchers measured the level of selenium in the blood
and, using the stored DNA, they determined the SOD2 genotype — the specific form of the SOD2 gene carried by each patient.
Simply having a high level of selenium was associated with a slightly
elevated risk of aggressive prostate cancer. But the risk was much more
strongly affected by the interaction of selenium levels and whether the
patient had a certain variant of the SOD2 gene.
Men with the highest selenium levels and the "AA" form of the SOD2
gene were 40 percent less likely to have been diagnosed with aggressive
prostate cancer than the men with same gene form but low levels of
But for men carrying the "V" form of the gene, selenium had the
opposite effect. In these men, those with the highest levels of selenium
in their blood were about twice as likely to have an aggressive type of
prostate cancer as their counterparts with low selenium levels.
The study couldn't determine whether any of the men had been taking
selenium supplements or not. But the researchers noted that men in the
large SELECT prevention trial had a much higher average selenium level
than those in the current study.
"Among the 25 percent of men with the AA genotype, having greater
selenium levels may protect against aggressive disease," the authors
concluded. "However, for the 75 percent of men who carry a V allele,
higher selenium levels might increase the likelihood of having worse
Therefore, they add, it is important to know which type of SOD2
gene a man has when considering the risks and potential benefits of
taking selenium supplements. Additionally, the authors say the effects
of the interaction between the SOD2 genotype and selenium may help explain apparently conflicting results of previous studies.
The results may seem counterintuitive to the public, who have been
told for years that antioxidants can help people live longer, healthier
lives with a lowered risk of cancer.
However, Kantoff says, "There is some precedent to this — research
has suggested that antioxidants could be protective if you don't have
cancer, but once you do, then antioxidants may be a bad thing."
In addition to Kantoff and Chan, other authors of the paper include
William Oh, MD, Wanling Xie, PhD, Meredith Regan, ScD, and Miyako Abe,
PhD, of Dana-Farber; Meir J. Stampfer DrPH, MD, of Brigham and Women's
Hospital and the Harvard School of Public Health, and Irena King, PhD,
of the Fred Hutchinson Cancer Research Center, Seattle.
The work was supported by grants from the National Cancer Institute and several foundations and charitable organizations.