Gene Expression Pathways in Prostate Tissue Associated with Vigorous Physical Activity in Prostate Cancer.
Journal
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
ISSN: 1538-7755
Titre abrégé: Cancer Epidemiol Biomarkers Prev
Pays: United States
ID NLM: 9200608
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
received:
14
10
2020
revised:
10
12
2020
accepted:
08
01
2021
pubmed:
28
1
2021
medline:
11
1
2022
entrez:
27
1
2021
Statut:
ppublish
Résumé
Men engaged in high physical activity have lower risks of advanced and fatal prostate cancer. Mechanisms underlying this association are not well understood but may include systemic and tumor-specific effects. We investigated potential mechanisms linking physical activity and gene expression in prostate tissue from men with prostate cancer. We included a subset of 118 men in the Health Professionals Follow-up Study diagnosed with prostate cancer between 1986 and 2005 with whole-transcriptome gene expression profiling on tumor and adjacent normal prostate tissue and physical activity data. Long-term vigorous physical activity was self-reported as the average time spent engaged in various forms of recreational physical activity at baseline and biennially until prostate cancer diagnosis. Gene set enrichment analysis was performed among KEGG and Hallmark gene sets to identify pathways with differential expression based on vigorous physical activity. In adjacent normal tissue, we identified 25 KEGG gene sets enriched (downregulated) in the highest compared with lowest quintile of vigorous physical activity at an FDR <0.10, including a number of cancer- and immune-related pathways. Although no gene sets reached statistical significance in tumor tissue, top gene sets differentially expressed included TGF beta, apoptosis, and p53 signaling pathways. These findings suggest that physical activity may influence the tumor microenvironment. Future studies are needed to confirm these findings and further investigate potential mechanisms linking physical activity to lethal prostate cancer. Identification of gene expression alterations in the prostate associated with physical activity can improve our understanding of prostate cancer etiology.
Sections du résumé
BACKGROUND
Men engaged in high physical activity have lower risks of advanced and fatal prostate cancer. Mechanisms underlying this association are not well understood but may include systemic and tumor-specific effects. We investigated potential mechanisms linking physical activity and gene expression in prostate tissue from men with prostate cancer.
METHODS
We included a subset of 118 men in the Health Professionals Follow-up Study diagnosed with prostate cancer between 1986 and 2005 with whole-transcriptome gene expression profiling on tumor and adjacent normal prostate tissue and physical activity data. Long-term vigorous physical activity was self-reported as the average time spent engaged in various forms of recreational physical activity at baseline and biennially until prostate cancer diagnosis. Gene set enrichment analysis was performed among KEGG and Hallmark gene sets to identify pathways with differential expression based on vigorous physical activity.
RESULTS
In adjacent normal tissue, we identified 25 KEGG gene sets enriched (downregulated) in the highest compared with lowest quintile of vigorous physical activity at an FDR <0.10, including a number of cancer- and immune-related pathways. Although no gene sets reached statistical significance in tumor tissue, top gene sets differentially expressed included TGF beta, apoptosis, and p53 signaling pathways.
CONCLUSIONS
These findings suggest that physical activity may influence the tumor microenvironment. Future studies are needed to confirm these findings and further investigate potential mechanisms linking physical activity to lethal prostate cancer.
IMPACT
Identification of gene expression alterations in the prostate associated with physical activity can improve our understanding of prostate cancer etiology.
Identifiants
pubmed: 33500320
pii: 1055-9965.EPI-20-1461
doi: 10.1158/1055-9965.EPI-20-1461
pmc: PMC8132456
mid: NIHMS1667178
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
751-756Subventions
Organisme : NCI NIH HHS
ID : P50 CA090381
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA167552
Pays : United States
Organisme : NIEHS NIH HHS
ID : T32 ES007069
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009001
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA136578
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA006516
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA113913
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA174206
Pays : United States
Informations de copyright
©2021 American Association for Cancer Research.
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