Changes in prostate gene expression in men undergoing an intensive nutrition and lifestyle intervention

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.exercise ͉ lifestyle changes ͉ prostate cancer ͉ SHOC2 ͉ stress management E pidemiological evidence (1, 2) and migrant studies (3) indicate that the incidence of clinically significant prostate cancer is much lower in parts of the world where people eat a predominantly low-fat, plant-based diet. We (4, 5) and others (6) have shown previously that diet and lifestyle interventions in men with earlystage prostate cancer decrease prostate-specific antigen (PSA) and decrease the rate of PSA increase. These studies provided some evidence that comprehensive lifestyle changes may have therapeutic potential in early prostate cancers. However, although these interventions are associated with decreased circulating insulin-like growth factor 1 (IGF1) (7), and although serum from men after intervention has reduced the ability to stimulate prostate cell-line growth in vitro (4), the actual molecular effects of these interventions in prostate tissue have not been previously examined.Many men with indolent prostate cancers detected by PSA screening will not exhibit disease progression during their lifetime; their treatment and associated side effects are unnecessary (8). We report here the results of the Gene Expressio...

Disproportionate Presentation of High Risk Prostate Cancer in a Safety Net Health System

“…25 Contemporary studies highlight that comprehensive lifestyle changes targeting these factors may modify the progression of prostate cancer in men with low risk disease, likely via pathways affecting gene expression and oncogene transcription. 26 Klassen et al examined prostate cancer risk in patients based on area resources such as race, income, education, neighborhood and community resources. 27 Those at highest risk for advanced tumor grade were white men with low income and all black men, suggesting the contribution of environment and psychosocial impact.…”

Expression Profiles of Loneliness-associated Genes for Survival Prediction in Cancer Patients

“…(Dusek et al, 2008;Ornish et al, 2008;Dein and Pargament 2012). More especially, many cancer patients were cured by just praying in Jesus' name for healing -these can be seen on YouTube.…”

Exercise therapy across the prostate cancer continuum

“…Notably, pathway analyses detected modifications of several pathways critical for tumorigenesis, including protein metabolism and modification, intracellular protein traffic and protein phosphorylation. 49 The above evidence suggests that exercise as part of a lifestyle modification program may have a beneficial effect for men with low-grade PC as evidenced by the decline in serum PSA, the in vitro inhibition of PC cell growth and the reduction in clinical events in the group adhering to the program as compared to the group receiving usual care. Furthermore, the hypothesis-generating alterations seen in gene expression provide a foundation to investigate molecular mechanisms responsible for the postulated association.…”

“…[47][48][49] Ornish et al 47 randomized 93 men with low-grade PC (Gleason sum o7) undergoing a watchful waiting protocol to a program of comprehensive lifestyle changes or a control group that received usual care. The program adherence rate was 95% in the experimental group and after 1 year these men had a statistically significant decrease in prostate-specific antigen (PSA) as compared to men in the control group.…”

“…Ornish et al 49 also examined the changes in prostate gene expression in a cohort of 30 men with low-risk PC who elected to undergo active surveillance. These men participated in an intensive lifestyle and nutrition program similar to the aforementioned study that included recommendations for moderate exercise.…”