Nonpharmacologic Strategies Have Mixed Results in Prostate Cancer Prevention

March 2012, Vol 3, No 2

San Francisco, CA—Nonpharmacologic strategies for prevention of cancer are potentially attractive and costeffective, but success stories are few. According to 2 separate studies presented at the recent Genitourinary Cancers Symposium, vigorous exercise prevented recurrence of prostate cancer and reduced mortality, whereas long-term vitamin E supplementation at commonly used doses actually increased the risk of prostate cancer in otherwise healthy men.

Value of Vigorous Exercise

Men who exercised vigorously at least 3 hours per week had favorable changes in gene expression patterns in normal prostate tissue, according to June M. Chan, MD, University of California at San Francisco, and colleagues. This study builds on a previous study showing that vigorous exercise slowed the progression of prostate cancer and reduced the number of prostate cancer deaths. "The favorable effects on gene expression may explain the protective effects of vigorous exercise," Dr Chan said. Vigorous exercise was defined as jogging, playing singles tennis, brisk walking, or any sustained exercise that accelerates the heart rate. The study included 70 men diagnosed with low-risk prostate cancer who were treated with watchful waiting. Prostate biopsies were obtained at baseline. Men who reported vigorous exercise at least 3 times per week (N = 23) showed different expression in 184 genes in normal prostate tissue compared with men who did not do vigorous exercise (N = 47).

Upregulated genes included the known tumor-suppressor genes BRCA1 and BRCA2. Gene-set analysis demonstrated that cell cycle and DNA repair pathways related to cancer were positively modulated in the men who reported vigorous exercise at least 3 times per week versus those who exercised less. These favorable effects on genes and pathways were not found in men who reported engaging in any type of physical activity—but not vigorous exercise—3 times per week, or those who did not exercise. The findings suggest that a certain threshold of intensity or duration of exercise may be important in reducing the risk of prostate recurrence. Larger studies are needed to replicate its findings.

Long-Term Vitamin E May Increased Risk for Prostate Cancer

The large, National Cancer Institute– sponsored Selenium and Vitamin E Cancer Prevention Trial (SELECT) suggests that healthy people should exercise caution in taking supplements without firm evidence. Long-term follow-up of the SELECT trial showed that vitamin E 400 IU/ day was associated with a 17% increased risk of developing prostate cancer when taken for 5.5 years by healthy men. The study also looked at the effect of selenium 200 mg/day alone or in combination with vitamin E, and found no increased risk of prostate cancer, as well as no benefit. SELECT enrolled 35,434 men aged ≥55 years (aged >50 years if they were black) at more than 400 study sites across the United States, Puerto Rico, and Canada. At an interim analysis in 2008, selenium 200 mg/day and vitamin E 400 IU/day alone or in combination had no effect on preventing prostate cancer in otherwise healthy men. The trial was halted early, and subjects stopped taking both supplements, but follow-up continued to determine long-term effects.

Longer-term follow-up found that for every 1000 men who took placebo, 65 cases of prostate cancer developed over 7 years. For every 1000 men who took vitamin E, 76 cases of prostate cancer developed. Updated results were presented by Eric J. Klein, MD, of the Cleveland Clinic Foundation, OH (Klein EJ, et al. JAMA. 2011;306:1549-1556). Dr Klein said that the supplement industry accounts for approximately $23 billion annually; approximately 50% of men aged >60 years take vitamin E, and approximately 23% take selenium for putative prevention of prostate cancer. SELECT suggests that taking vitamin E is in fact harmful, whereas taking selenium has no positive effect.

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