Vigorous Physical Activity Is Associated with Lower Risk of Metastatic-Lethal Progression in Prostate Cancer and Hypomethylation in the Gene.

BACKGROUND

There is preliminary evidence linking physical activity to better prostate cancer outcomes, though the molecular mechanisms underlying this association are not clear.

METHODS

In a Seattle-based cohort of patients diagnosed with clinically localized prostate cancer and prospective follow-up for outcomes ( = 1,354), we studied 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 (Infinium HumanMethylation450 BeadChip array) and exercise ( = 524).

RESULTS

Patients who had vigorous physical activity at least once per week during the year before diagnosis (∼79% of the cohort) were significantly less likely to progress to metastatic-lethal prostate cancer compared with those who had vigorous physical activity less frequently (adjusted hazard ratio = 0.63; = 0.029). Among the subset of men who had radical prostatectomy as primary treatment and tumor tissue available, a differentially methylated region (DMR) was identified (family-wise error rate = 0.03, hypomethylated in the weekly exercise group), with 9 methylation probes located in the promoter region of . This gene encodes a calcium binding protein involved in innate immune response. The methylation level of the nine CpGs was inversely correlated with gene expression (average correlation coefficient = -0.35).

CONCLUSIONS

Vigorous physical activity before diagnosis is associated with epigenetic alterations of and prostate cancer metastatic-lethal progression.

IMPACT

This analysis provides strong evidence for the association between vigorous physical activity and a less likelihood to develop metastatic-lethal progression, and a suggestive link between exercise and DNA methylation in the gene.