Vitamin E, selenium may alter genes in prostate cancer: Study

Writing in the Journal of the National Cancer Institute​, scientists from the University of Texas MD Anderson Cancer Center in Houston report that exposure of biopsy samples from people with cancer to vitamin E, selenium or both, expressed different genes, with the combined exposure producing results similar to that observed in people with no prostate cancer.

“To the best of our knowledge, this study was the first detailed systematic pathological interrogation to be completed in preoperative patients with favourable risk prostate cancer,”​ wrote lead author Dimitra Tsavachidou.

The controversy​

A number of studies, most notably the Nutritional Prevention of Cancer study and the Alpha-tocopherol, Beta-carotene Cancer Prevention study, have reported that the nutrients, alone or in combination, may reduce the risk of prostate cancer.

With over half a million new cases of prostate cancer are diagnosed every year world wide, and the cancer directly causing over 200,000 deaths, potential preventive measures are highly desirable. Despite great promise over vitamin E and selenium, recent results from the Selenium and Vitamin E Cancer Prevention Trial (SELECT) reported no significant differences between any of the groups in relation to prostate cancer risk.

The results were greeted with disappointment, while many in both academia and industry indicating that, given positive results from previous clinical trials and epidemiological studies, the design of SELECT, including the supplements used, may have undermined the results.

Indeed, Peter Gann, MD, ScD, from the University of Illinois at Chicago, commented in an editorial in the Journal of the American Medical Association​ (Vol. 301, doi:10.1001/jama.2008.863) that: “...single-agent interventions, even in combinations, may be an ineffective approach to primary prevention in average-risk populations. ​

“It may be time to give up the idea that the protective influence of diet on prostate cancer risk...can be emulated by isolated dietary molecules given alone or in combination to middle-aged and older men,”​ added Gann.

The new data from Texas adds to the debate and appears to indicate that, at a gene expression level at least, vitamin E and selenium do offer protection against prostate cancer.

The door creaks open again​

Tsavachidou and her co-workers took prostate biopsy samples from surgically removed prostate after pre-operative treatment with vitamin supplements in order to investigate if there are any effects on gene expression.

The researchers report that the expression of certain genes did differ between tumour samples from patients who had taken vitamin E (400 IU, all-rac-alpha-tocopherol), selenium (200 micrograms of L-selenomethionine), both supplements, or placebo.

The study, which involved 39 patients and lasted for between three and six weeks, found that gene expression patterns differed between the groups. Indeed, the expression of several pathways associated with cancer was altered in the supplement groups compared with the placebo group.

Notably, the researchers reported an change in the expression of the TP53 gene, which codes for p53, an important protein involved in the functioning of a normal cell cycle and acting as a tumour suppressor.

“These p53 findings are also consistent with those in proteomic studies of patients’ serum in which combined […] selenium and vitamin E induced protein expression patterns that were indicative of being free of prostate cancer,”​ wrote Tsavachidou and her co-workers.

So, where do we stand?​

In an insightful accompanying editorial in the JNCI, Eric Klein, MD, from the Glickman Urological and Kidney Institute in Ohio, said the new study is “… noteworthy for demonstrating that even short-term exposure (i.e., 3 ​– 6 weeks) to these agents can affect expression of a majority of the genes interrogated and, in the robust demonstration of the utility of the preprostatectomy model, for deriving information on modulation of biomarkers.”​

“Certainly, the findings lend credence to the previous evidence that selenium and vitamin E might be active as cancer preventatives,”​ added Dr Klein.

In an attempt to rationalise the differences between epidemiological and in vitro​ studies and randomised trials like SELECT, Klein said that randomized controlled trials “do not always validate what we believe biology indicates and that our model systems are imperfect measures of clinical outcomes in the real world”​.

Source: Journal of the National Cancer Institute​March 2009, Volume 101, Issue 5, Pages 306-320“Selenium and Vitamin E: Cell Type- and Intervention-Specific Tissue Effects in Prostate Cancer”​Authors: D. Tsavachidou, T.J. McDonnell, S. Wen, X. Wang et al.

Editorial: Journal of the National Cancer Institute​March 2009, Volume 101, Issue 5, Pages 283-285“Selenium and Vitamin E: Interesting Biology and Dashed Hope”​Author: E.A. Klein