Analysis may explain exercise-prostate cancer progression link

Key Points

San Francisco-A recent study may have found the genetic mechanism behind the potential association between vigorous exercise and a reduced risk of prostate cancer progression and prostate cancer-specific mortality in men with localized disease.

"There is increasing evidence that more physical activity may improve clinical outcomes among men with prostate cancer," said lead author Mark Jesus M. Magbanua, PhD, a postdoctoral fellow at the University of California, San Francisco.

"All we have are observational data so far, but the observations suggest that vigorous physical activity upregulates genes that may offer a protective effect in men with localized prostate cancer," added Dr. Magbanua, who presented the study data at the 2012 Genitourinary Cancers Symposium in San Francisco.

On a related track, one of the lead investigators of the nutritional supplements trial and senior author of the current study, June M. Chan, ScD, had reported that men who exercise tend to fare better than similar men who do not exercise after a prostate cancer diagnosis (Cancer Res 2011; 71:3889-95). Other observational studies have reported a similar association between vigorous exercise and clinical outcomes in breast, colorectal, and other cancers.

But the observation that exercise can influence clinical outcomes did not suggest a mechanism. Dr. Chan's group used gene expression analysis from normal prostate tissue samples from 70 men who had chosen active surveillance rather than active treatment for low-risk localized prostate cancer. Of the 70 men, 23 engaged in vigorous physical activity such as running, jogging, or cycling for at least 3 hours each week. The other 47 either did not engage in regular physical activity or engaged in less vigorous activity such as brisk walking.

Gene expression analysis found 184 significant genes that were differentially expressed in the two groups. Genes that were upregulated included two known tumor suppressor genes, BRCA1 and BRCA2.

Duration, nature of physical activity key

Gene pathway analysis showed that both cell cycle and DNA repair pathways were positively modulated in men who engaged in vigorous activity for at least 3 hours per week. Men who did not exercise regularly or exercised less vigorously did not show any differential gene expression. That suggests that both duration of physical activity-at least 3 hours weekly-and engaging in vigorous activity are important, Dr. Magbanua said.

In this initial small sample, body mass index did not appear to play a role in upregulation of potentially beneficial genes, he added. There was no difference in gene expression between men with a BMI less than 25 kg/m² compared to men with a BMI of 25 kg/m² or higher.

"Vigorous physical activity is part of a healthy lifestyle," Dr. Magbanua said. "Exercise and overall wellness are likely important for patients with prostate cancer. These data, while preliminary, suggest mechanisms by which exercise may confer specific benefits to men with prostate cancer. Understanding the molecular mechanisms by which this kind of physical activity affects gene expression may help develop strategies to delay or even prevent prostate cancer progression."

These observational data suggest a need for larger confirmational studies as well as similar studies in men with more advanced and recurrent disease. Researchers are still following the 70 men to collect longer-term outcome and exercise data, Dr. Magbanua said. The group is also collaborating with other teams to develop patient education strategies that reinforce the value of physical activity and other healthy lifestyle practices that could improve prostate cancer outcomes.