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Vigorous physical activity is associated with metastatic-lethal progression in prostate cancer and differential tumor DNA methylation in the CRACR2A gene
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November 21 2018
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Source: Cancer Epidemiol Biomarkers Prev. 28(2):258-264
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Details:
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Alternative Title:Cancer Epidemiol Biomarkers Prev
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Personal Author:
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Description:Background:
There is preliminary evidence linking physical activity to better prostate cancer (PCa) outcomes, though the molecular mechanisms underlying this association are not clear.
Methods:
In a Seattle-based cohort of patients diagnosed with clinically localized PCa and prospective follow-up for outcomes (n=1354), we studied the association between self-reported vigorous physical activity and PCa progression to a metastatic-lethal phenotype. A subset of patients have prostate cancer tissue samples available for investigating DNA methylation (Infinium® HumanMethylation450 BeadChip array) and exercise (n=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 PCa compared to those who had vigorous physical activity less frequently (adjusted hazard ratio =0.63, p-value=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, hypo-methylated in the weekly exercise group), with 9 methylation probes located in the promoter region of CRACR2A. This gene encodes a calcium binding protein involved in innate immune response. The methylation level of the nine CpGs was inversely correlated with CRACR2A gene expression (average correlation coefficient= – 0.35).
Conclusions:
Vigorous physical activity before diagnosis is associated with epigenetic alterations of CRACR2A and PCa 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 CRACRA2A gene.
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Pubmed ID:30464020
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Pubmed Central ID:PMC6363836
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Document Type:
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Funding:P30 CA015704/NCI NIH HHS/National Cancer Institute/United States ; P50 CA097186/NCI NIH HHS/National Cancer Institute/United States ; R01 CA222833/NCI NIH HHS/National Cancer Institute/United States ; R01 CA056678/NCI NIH HHS/National Cancer Institute/United States ; K05 CA175147/NCI NIH HHS/National Cancer Institute/United States ; ... More +
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