In a cohort of patients diagnosed with clinically localized prostate cancer, vigorous physical activity was associated with less likelihood of developing metastatic-lethal progression and epigenetic alterations of CRACRA2A gene. The Seattle-based study of 1,354 patients examined the association between self-reported vigorous physical activity and prostate cancer progression to a metastatic-lethal phenotype. A subset of patients had prostate cancer tissue samples available for investigating DNA methylation and exercise (n=524). Researchers found:
- Patients who reported vigorous physical activity at least once per week during the year before diagnosis (~70% of the cohort) were significantly less likely to progress to metastatic-lethal prostate cancer compared with those who reported physical activity less frequently.
- Among the subset of men who had radical prostatectomy as primary treatment and tumor tissue available, a differentially methylated region was identified, with 9 methylation probes located in the promoter region of CRACR2A.
- The methylation level of the 9 CpGs was inversely correlated with CRACR2A gene expression.
Dai JY, Wang B, Wang X, et al. Vigorous physical activity is associated with lower risk of metastatic-lethal progression in prostate cancer and hypomethylation in the CRACR2A gene. Cancer Epidemiol Biomarkers Prev. 2019;28(2):258-264. doi:10.1158/1055-9965.
Dai et al. present an extremely interesting study that suggests there is a potential association of increased physical activity with a concomitant decrease in prostate cancer progression. Even more compelling is that this group evaluated the hypothesis that gene methylation may be a mechanism for such an association. One would expect methylation or mRNA expression profiles to be more quickly responsive to external pressures such as physical activity as compared to mutation or copy number variations. This study provides a good basis on which to build randomized trials to further evaluate whether physical activity may result in decreased prostate cancer progression. —Mark A. Klein, MD