Statin Use Is Associated with Lower Risk of PTEN-Null and Lethal Prostate Cancer.
Adult
Aged
Biomarkers, Tumor
/ genetics
Follow-Up Studies
Gene Expression Regulation, Neoplastic
/ drug effects
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors
/ therapeutic use
Incidence
Male
Middle Aged
Neoplasm Metastasis
PTEN Phosphohydrolase
/ genetics
Prospective Studies
Prostatic Neoplasms
/ drug therapy
Risk Assessment
Risk Factors
Survival Rate
Transcriptional Regulator ERG
/ genetics
United States
/ epidemiology
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
01 03 2020
01 03 2020
Historique:
received:
29
08
2019
revised:
22
10
2019
accepted:
15
11
2019
pubmed:
23
11
2019
medline:
5
1
2021
entrez:
23
11
2019
Statut:
ppublish
Résumé
Statins are associated with lower risk of aggressive prostate cancer, but lethal prostate cancer is understudied and contributing mechanisms are unclear. We prospectively examined statins and lethal prostate cancer risk in the Health Professionals Follow-up Study (HPFS), tested associations with molecular subtypes, and integrated gene expression profiling to identify putative mechanisms. Our study included 44,126 men cancer-free in 1990, followed for prostate cancer incidence through 2014, with statin use recorded on biennial questionnaires. We used multivariable Cox regression to examine associations between statins and prostate cancer risk overall, by measures of clinically significant disease, and by ERG and PTEN status. In an exploratory analysis, age-adjusted gene set enrichment analysis identified statin-associated pathways enriched in tumor and adjacent normal prostate tissue. During 24 years of follow-up, 6,305 prostate cancers were diagnosed and 801 (13%) were lethal (metastatic at diagnosis or metastatic/fatal during follow-up). Relative to never/past use, current statin use was inversely associated with risk of lethal prostate cancer [HR, 0.76; 95% confidence interval (CI), 0.60-0.96] but not overall disease. We found a strong inverse association for risk of PTEN-null cancers (HR, 0.40; 95% CI, 0.19-0.87) but not PTEN-intact cancers (HR, 1.18; 95% CI, 0.95-1.48; Molecular tumor classification identified PTEN and inflammation/immune activation as potential mechanisms linking statins with lower lethal prostate cancer risk. These findings support a potential causal association and could inform selection of relevant biomarkers for statin clinical trials.
Identifiants
pubmed: 31754047
pii: 1078-0432.CCR-19-2853
doi: 10.1158/1078-0432.CCR-19-2853
pmc: PMC7056554
mid: NIHMS1544271
doi:
Substances chimiques
Biomarkers, Tumor
0
ERG protein, human
0
Hydroxymethylglutaryl-CoA Reductase Inhibitors
0
Transcriptional Regulator ERG
0
PTEN Phosphohydrolase
EC 3.1.3.67
PTEN protein, human
EC 3.1.3.67
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1086-1093Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA090381
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA136578
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA167552
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA006516
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA006973
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
©2019 American Association for Cancer Research.
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