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Cancer Epidemiology, Biomarkers & Prevention
Cancer Epidemiology, Biomarkers & Prevention

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Vigorous Physical Activity Is Associated with Lower Risk of Metastatic–Lethal Progression in Prostate Cancer and Hypomethylation in the CRACR2A Gene

James Y. Dai, Bo Wang, Xiaoyu Wang, Anqi Cheng, Suzanne Kolb, Janet L. Stanford and Jonathan L. Wright
James Y. Dai
Division of Public Health Sciences, Fred Hutchison Cancer Research Center, Seattle, Washington.Department of Biostatistics, University of Washington School of Public Health, Seattle, Washington.
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  • For correspondence: jdai@fredhutch.orgjstanfor@fredhutch.org
Bo Wang
Department of Laboratory Medicine, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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Xiaoyu Wang
Division of Public Health Sciences, Fred Hutchison Cancer Research Center, Seattle, Washington.
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Anqi Cheng
Department of Biostatistics, University of Washington School of Public Health, Seattle, Washington.
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Suzanne Kolb
Division of Public Health Sciences, Fred Hutchison Cancer Research Center, Seattle, Washington.
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  • ORCID record for Suzanne Kolb
Janet L. Stanford
Division of Public Health Sciences, Fred Hutchison Cancer Research Center, Seattle, Washington.Department of Epidemiology, University of Washington School of Public Health, Seattle, Washington.
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  • For correspondence: jdai@fredhutch.orgjstanfor@fredhutch.org
Jonathan L. Wright
Division of Public Health Sciences, Fred Hutchison Cancer Research Center, Seattle, Washington.Department of Urology, University of Washington School of Medicine, Seattle, Washington.
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DOI: 10.1158/1055-9965.EPI-18-0622 Published February 2019
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Abstract

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 (n = 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 (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 prostate cancer compared with those who had vigorous physical activity less frequently (adjusted hazard ratio = 0.63; P = 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 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 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 CRACRA2A gene.

This article is featured in Highlights of This Issue, p. 237

  • Received June 3, 2018.
  • Revision received September 13, 2018.
  • Accepted November 6, 2018.
  • Published first November 21, 2018.
  • ©2018 American Association for Cancer Research.
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Cancer Epidemiology Biomarkers & Prevention: 28 (2)
February 2019
Volume 28, Issue 2
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Vigorous Physical Activity Is Associated with Lower Risk of Metastatic–Lethal Progression in Prostate Cancer and Hypomethylation in the CRACR2A Gene
James Y. Dai, Bo Wang, Xiaoyu Wang, Anqi Cheng, Suzanne Kolb, Janet L. Stanford and Jonathan L. Wright
Cancer Epidemiol Biomarkers Prev February 1 2019 (28) (2) 258-264; DOI: 10.1158/1055-9965.EPI-18-0622

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Vigorous Physical Activity Is Associated with Lower Risk of Metastatic–Lethal Progression in Prostate Cancer and Hypomethylation in the CRACR2A Gene
James Y. Dai, Bo Wang, Xiaoyu Wang, Anqi Cheng, Suzanne Kolb, Janet L. Stanford and Jonathan L. Wright
Cancer Epidemiol Biomarkers Prev February 1 2019 (28) (2) 258-264; DOI: 10.1158/1055-9965.EPI-18-0622
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