July 1, 2009 — "If you already have prostate cancer, it may be a bad thing to take selenium," says the senior author of a new study published online June 15 in the Journal of Clinical Oncology.
Selenium supplements have been sold and promoted as a means of preventing prostate cancer, but the large SELECT prevention trial recently showed no effect on the incidence rate. Now this latest study suggests the potential for harm in patients who already have prostate cancer.
In the study, Philip Kantoff, MD, director of genitourinary oncology at the Dana-Farber Cancer Institute at the University of California, San Francisco, and colleagues found that having a high level of selenium in the blood was associated with a slightly elevated risk of aggressive prostate cancer.
But the risk was particularly elevated in men who also had a certain variant of the gene coding for manganese superoxide dismutase (SOD2). For these men, who made up 75% of the study population, having "high selenium levels might increase the likelihood of having worse characteristics," the researchers concluded.
The results were unexpected, and they are the first to raise concern about potentially harmful consequences of taking supplemental selenium. Until further data are available to sort out which men can safely take the supplement, Dr. Kantoff told Medscape Oncology that he would advise patients with prostate cancer not to take supplements containing selenium.
Interaction Between Selenium and Genotype
The study involved 489 patients who had been diagnosed with prostate cancer at the Dana Farber Center between 1994 and 2001. These men had a mean age of 62 years and mean level of prostate specific antigen (PSA) of 6.0 ng/mL. More than half had good-risk disease, while about a third had intermediate-risk disease, the researchers comment.
The team examined banked blood samples for selenium levels and also for genomic DNA, in particular genotyping for the SOD2 polymorphism: 25% of patients were found to carry the A form of the gene, and 75% carried the V form of the gene.
Dr. Kantoff and colleagues found that having higher vs lower selenium blood levels was associated with a slightly increased likelihood of presenting with aggressive disease (relative risk, 1.35). The mean selenium level (121.4 ng/mL) in this patient population was similar to that reported in several other studies (ranging between 108 and 141 ng/mL), the researchers comment.
There was no way of knowing which patients had been taking selenium supplements, the researchers comment. But they note that the levels measured in this study were substantially lower than the median level (252 ng/mL) in men who were taking selenium supplements in the large SELECT prevention study.
This study found no effect of SOD2 genotype on disease aggressiveness, although this effect has been reported previously both by this team and others.
However, there was evidence of an interaction between the SOD2 genotype and selenium levels.
Among men with the AA genotype, higher selenium levels were associated with a 40% reduced risk of presenting with aggressive disease (relative risk, 0.60), while among men with the V allele (either VV or VA genotype), higher selenium levels were associated with an almost doubling of the risk of aggressive disease (relative risk, 1.82; P = .007 for the interaction).
"It is possible that selenium helps some and may harm others," Dr. Kantoff commented to Medscape Oncology. "Genetic studies will help sort this out. Until then, I would not advise taking selenium supplements," he said.
Potential Harm Not Previously Reported
The direct relation of higher selenium with more aggressive disease among V-allele carriers was "unexpected and has not been previously reported," say the researchers.
"One explanation may be that in men with established cancer, antioxidants may promote cancer-cell survival through an antiapoptotic mechanism by neutralizing the higher levels of reactive oxygen species found in cancer cells," they speculate. However, there could be other explanations, and the finding may also be due to chance and so needs confirmation, they add.
"These data suggest that the relationship between circulating selenium levels at diagnosis and the prognostic risk of prostate cancer is modified by the SOD2 genotype and indicate caution against broad use of selenium supplementation for men with prostate cancer," the authors conclude.
Prevention Study Found No Benefit
These new findings are also "interesting, particularly in light of the recent negative results from the SELECT prevention study," Dr. Kantoff commented in a statement.
The SELECT study set out to discover whether taking selenium and vitamin-E supplements would offer protection against prostate cancer, but the trial was stopped early in October 2008 because of an apparent lack of benefit and a possibility of harm, as reported by Medscape Oncology.
Selenium supplements' reputation for prevention, sold and promoted as a means of preventing prostate cancer, is largely based on observational studies that found a higher risk for prostate-cancer incidence and mortality in geographical areas that were naturally low in selenium. But studies with selenium as a preventive have shown mixed results.
However, after announcing the results from the huge SELECT study, which involved 35,000 men, lead author Larry Baker, MD, professor of medicine at the University of Michigan Medical School, in Ann Arbor, said: "This is the definitive study, and anyone who argues against it is ignoring the facts."
Dr. Kantoff tells Medscape Oncology that it is now "essential" to go back and genotype the samples in the SELECT trial. "There may be some people who benefit and some who do not or are even harmed."
No conflicts of interest were reported.
J Clin Oncol. Published online June 15, 2009. Abstract
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου