Intensive nutrition and lifestyle changes may modulate gene expression

Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0803080105
Changes in prostate gene expression in men undergoing an intensive nutrition and lifestyle intervention

Dean Ornish*, Mark Jesus M. Magbanua, Gerdi Weidner*, Vivian Weinberg¶, Colleen Kemp*, Christopher Green, Michael D. Mattie, Ruth Marlin*, Jeff Simko||, Katsuto Shinohara, Christopher M. Haqq, and Peter R. Carroll

Department of Urology, The Helen Diller Family Comprehensive Cancer Center, and ||Department of Pathology, University of California, 2340 Sutter Street, San Francisco, CA 94115; *Preventive Medicine Research Institute, 900 Bridgeway, Sausalito, CA 94965; Department of Medicine, School of Medicine, University of California, 505 Parnassus Avenue, San Francisco, CA 94143; and ¶Biostatistics Core, The Helen Diller Family Comprehensive Cancer Center, University of California, 513 Parnassus Avenue, Box 0127, San Francisco, CA 94143

Communicated by J. Craig Venter, The J. Craig Venter Institute, Rockville, MD, April 2, 2008 (received for review February 13,2008)

Abstract

Epidemiological and prospective studies indicate that comprehensive lifestyle changes may modify the progression of prostate cancer.
However, the molecular mechanisms by which improvements in diet and lifestyle might affect the prostate microenvironment are poorly understood.

We conducted a pilot study to examine changes in prostate gene expression in a unique population of men with low-risk prostate cancer who declined immediate surgery, hormonal therapy, or radiation and participated in an intensive nutrition and lifestyle intervention while undergoing careful surveillance for tumor progression.

Consistent with previous studies, significant improvements in weight, abdominal obesity, blood pressure, and lipid profile were observed (all P < 0.05), and surveillance of low-risk patients was safe.

Gene expression profiles were obtained from 30 participants, pairing RNA samples from control prostate needle biopsy taken before intervention to RNA from the same patient's 3-month postintervention biopsy. Quantitative real-time PCR was used to validate array observations for selected transcripts.

Two-class paired analysis of global gene expression using significance analysis of microarrays detected 48 up-regulated and 453 down-regulated transcripts after the intervention.

Pathway analysis identified significant modulation of biological processes that have critical roles in tumorigenesis, including protein metabolism and modification, intracellular protein traffic, and protein phosphorylation (all P < 0.05).

Intensive nutrition and lifestyle changes may modulate gene expression in the prostate.

Understanding the prostate molecular response to comprehensive lifestyle changes may strengthen efforts to develop effective prevention and treatment. Larger clinical trials are warranted to confirm the results of this pilot study.