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Supplement Use Alters Some Prostate Cancer Gene Expression

NEW YORK (GenomeWeb News) – Taking selenium and/or vitamin E supplements prior to prostate cancer surgery can alter gene expression of tissue that is removed, according to a paper appearing online yesterday in the Journal of the National Cancer Institute.

Researchers from Texas and Washington State used a randomized, placebo-controlled phase IIA study to assess whether giving vitamin E, selenium, or both supplements to a few dozen prostate cancer patients before surgery altered gene expression in their normal cells or in stromal and tumor cells from different prostate zones after prostatectomy.

The team did detect differential gene expression following supplement use. But the nature and magnitude of these expression changes varied by tissue type. And, researchers cautioned, large clinical trials have not found corresponding prostate cancer prevention associated with such supplement use.

The study was intended to complement the Selenium and Vitamin E Cancer Prevention Trial or SELECT, a National Institutes of Health-sponsored study of more than 35,000 men to determine whether vitamin E, selenium, or combinations of the two supplements decrease prostate cancer risk.

SELECT was initially intended to run from 2001 to 2013. But last October, study participants were told to stop taking the supplements after an independent Data and Safety Monitoring Committee met in September and determined that selenium and vitamin E, alone or together, did not appear to prevent prostate cancer. Participant health will be monitored for roughly three more years, according to the National Cancer Institute's web site.

Vitamin E is a fat soluble vitamin found in foods such as nuts, vegetable oils, leafy green vegetables, and fortified cereals. Selenium, meanwhile, is an essential mineral required in small amounts. It's found in some meats, grains, and plants — especially those grown in selenium-rich soil. Both selenium and alpha-tocopherol, the most active form of vitamin E, are antioxidants, compounds that protect cells from free radical damage.

Previous research hinted that vitamin E and/or selenium might have cancer-fighting benefits — including secondary analyses of two phase III clinical trials and other studies that linked low selenium levels with increased prostate cancer risk and decreased treatment effectiveness.

In an effort to understand the supplements' effect on prostate cancer and normal cells, if any, senior author Jeri Kim, a genitourinary researcher at the University of Texas MD Anderson Cancer Center, and her team did a randomized, double-blind, phase IIA trial of 39 men with organ-confined prostate cancer. The men were randomly assigned take a placebo, 200 micrograms of selenium, 400 International Units of vitamin E, or both for three to six weeks before their prostatectomy surgery.

The researchers evaluated gene expression in prostate tumor cells and stromal cells from different zones of the prostate gland as well as normal tissue using Affymetrix Hu133A arrays. The team validated these findings using real-time quantitative PCR. Pre- and post-treatment blood samples were also collected for each group.

The researchers found that both supplements were linked to gene expression changes in different cell types, though overall gene expression patterns "were not statistically significantly different by treatment group."

For instance, taking selenium was linked to altered expression of 1,329 genes in normal skin cells, 1,354 genes in stromal cells, and 329 genes in tumor cells.

When they did pathway analysis, they found that taking a combination of the supplements appeared to influence the expression of genes involved in tumor suppressor and cellular proliferation pathways, including the p53 and NFKB pathways.

The team reported that patient exposure to selenium seemed to bump up p53 expression, though this increase was only borderline statistically significant. Meanwhile, vitamin E alone or vitamin E plus selenium were both linked to increased TP53 expression in normal cells. The supplements were also linked to expression changes in pathways influencing androgen receptor activity and apoptosis.

In an editorial appearing in the same issue of JCNI, Eric Klein, a researcher at the Cleveland Clinic Lerner College of Medicine's Glickman Urological and Kidney Institute, said, "The findings lend credence to the previous evidence that selenium and vitamin E might be active as cancer preventatives."

But, he warned that although the results are interesting, they are not mirrored by outcomes from SELECT, where "neither selenium nor vitamin E in the same doses and formulations used in the [this study] had any beneficial effect on major health outcomes."

Indeed, among their study's limitations, Kim and colleagues noted that, "A large chemoprevention trial of selenium and vitamin E showed no evidence of a preventive effect, and so any supplement-induced changes in gene expression are not likely to predict for prevention efficacy."

To try to understand such discrepancies, Klein suggested that researchers need to come up with new strategies to understand and assess biological complexity.

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