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Diet, Exercise Affect Prostate Gene Expression

NEW YORK (GenomeWeb News) – Diet, exercise, and other lifestyle changes can have profound and rapid effects on gene expression, new research suggests.
In a paper appearing online last night in the Proceedings of the National Academy of Sciences, a team of California researchers followed dozens of men with early-stage, low-risk prostate cancer over three months as they changed their diet, got more exercise, and engaged in stress-management activities. The team then compared the gene expression in prostate tissue of each before and after the lifestyle intervention, detecting altered expression of some 500 genes — including some associated with cancer risk.
Calling the findings a potential antidote to “genetic nihilism,” lead author Dean Ornish, founder, president, and director of the Preventive Medicine Research Institute in Sausalito, said that the work may convince some that “our genes are our predispositions, but they may not be our fate.”
As part of the “Gene Expression Modulation by Intervention with Nutrition and Lifestyle” or GEMINAL study, the team enrolled 31 men between the ages of 49 and 80 years old with low-risk prostate cancer. Because their tumors were not deemed aggressive, the men opted for active surveillance and lifestyle interventions rather than conventional surgical or radiation treatment.
Participants cut their fat consumption and increased their intake of fruits, vegetables, whole grains, soy, and, legumes. They also upped the amount of exercise they got to about three hours a week of moderate aerobic activity and participated in stress management programs (an hour a day of yoga-based stretching and an hour a week in a group support session).
At baseline and again after three months, the researchers measured waist circumference, height and weight, serum lipid, C-reactive protein, and prostate-specific antigen levels. They also compared gene expression levels in the normal prostate tissue of 30 patients at baseline and again three months after treatment started using microarrays that looked at 40,000 sites across the genome.
On average, participants’ waists shrank by about three inches. Their triglyceride and C-reactive protein levels tended to go down, too, though those results weren’t statistically significant. One patient required surgery because of tumor growth and, overall, PSA levels didn’t change within the group.
Gene expression did change, though. After three months of lifestyle intervention, the researchers found that the expression of 48 genes went up, while that of 453 went down.
In general, the researchers said, the expression of genes believed to promote disease declined, while disease-preventing genes were up-regulated. For example, the expression of certain oncogenes and genes in pathways involved in processes such as protein metabolism, trafficking, and phosphorylation tended to be curbed.
“To find that more than 450 genes were down-regulated by the diet and lifestyle intervention was extremely exciting and certainly, I think, exceeding my expectation when we started the study,” University of California at San Francisco urologist Chris Haqq, one of the senior authors on the paper, told reporters during a conference call to discuss the work.
The scientists also noted that since the changes were detected in normal prostate rather than tumor tissue, they may have implications for those who don’t have prostate cancer too. “It’s certainly a very striking result and gives us a lot of molecular insight into what healthy changes in diet and lifestyle actually do to healthy tissues,” Haqq said.
The researchers emphasized the need for additional research, including larger clinical trials with control patients and experiments to measure protein levels before and after similar lifestyle interventions. Still, they expressed enthusiasm about the results.
Haqq noted that the study not only provides insights into potential drug targets, but also suggests that lifestyle changes could produce benefits akin to therapeutic interventions. Citing the decrease in low-density-lipoprotein or LDL cholesterol observed in the patients, Haqq said a drug with similar effects would be a “blockbuster homerun.”

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