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Digoxin and prostate cancer survival in the Finnish Randomized Study of Screening for Prostate Cancer.

ABSTRACT: Protective effects have been suggested for digoxin against prostate cancer risk. However, few studies have evaluated the possible effects on prostate cancer-specific survival. We studied the association between use of digoxin or beta-blocker sotalol and prostate cancer-specific survival as compared with users of other antiarrhythmic drugs in a retrospective cohort study.Our study population consisted of 6537 prostate cancer cases from the Finnish Randomized Study of Screening for Prostate Cancer diagnosed during 1996-2009 (485 digoxin users). The median exposure for digoxin was 480 DDDs (interquartile range 100-1400 DDDs). During a median follow-up of 7.5 years after diagnosis, 617 men (48 digoxin users) died of prostate cancer. We collected information on antiarrhythmic drug purchases from the national prescription database. Both prediagnostic and postdiagnostic drug usages were analysed using the Cox regression method.No association was found for prostate cancer death with digoxin usage before (HR 1.00, 95% CI 0.56-1.80) or after (HR 0.81, 95% CI 0.43-1.51) prostate cancer diagnosis. The results were also comparable for sotalol and antiarrhythmic drugs in general. Among men not receiving hormonal therapy, prediagnostic digoxin usage was associated with prolonged prostate cancer survival (HR 0.20, 95% CI 0.05-0.86).No general protective effects against prostate cancer were observed for digoxin or sotalol usage.

SUBMITTER: Kaapu KJ

PROVIDER: S-EPMC5129833 | biostudies-other | 2016 Nov

REPOSITORIES: biostudies-other

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Digoxin and prostate cancer survival in the Finnish Randomized Study of Screening for Prostate Cancer.

Kaapu Kalle J KJ Murtola Teemu J TJ Talala Kirsi K Taari Kimmo K Tammela Teuvo Lj TL Auvinen Anssi A

British journal of cancer 20161018 11

<h4>Background</h4>Protective effects have been suggested for digoxin against prostate cancer risk. However, few studies have evaluated the possible effects on prostate cancer-specific survival. We studied the association between use of digoxin or beta-blocker sotalol and prostate cancer-specific survival as compared with users of other antiarrhythmic drugs in a retrospective cohort study.<h4>Methods</h4>Our study population consisted of 6537 prostate cancer cases from the Finnish Randomized Stu ...[more]

PMID: 27755533

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Project description:BackgroundAbnormal metabolism and perturbations in metabolic pathways play significant roles in the development and progression of prostate cancer; however, comprehensive metabolomic analyses of human data are lacking and needed to elucidate the interrelationships.MethodsWe examined the serum metabolome in relation to prostate cancer survival in a cohort of 1812 cases in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. Using an ultrahigh-performance LC-MS/MS platform, we identified 961 known metabolites in prospectively collected serum. Median survival time from diagnosis to prostate cancer-specific death (N=472) was 6.6 years (interquartile range=2.9-11.1 years). Cox proportional hazards regression models estimated hazard ratios and 95% confidence intervals of the associations between the serum metabolites (in quartiles) and prostate cancer death, adjusted for age at baseline and diagnosis, disease stage, and Gleason sum. In order to calculate risk scores, we first randomly divided the metabolomic data into a discovery set (70%) and validated in a replication set (30%).ResultsOverall, 49 metabolites were associated with prostate cancer survival after Bonferroni correction. Notably, higher levels of the phospholipid choline, amino acid glutamate, long-chain polyunsaturated fatty acid (n6) arachidonate (20:4n6), and glutamyl amino acids gamma-glutamylglutamate, gamma-glutamylglycine, and gamma-glutamylleucine were associated with increased risk of prostate cancer-specific mortality (fourth versus first quartile HRs=2.07-2.14; P-values <5.2×10-5). By contrast, the ascorbate/aldarate metabolite oxalate, xenobiotics S-carboxymethyl-L-cysteine, fibrinogen cleavage peptides ADpSGEGDFXAEGGGVR and fibrinopeptide B (1-12) were related to reduced disease-specific mortality (fourth versus first quartile HRs=0.82-0.84; P-value <5.2×10-5). Further adjustment for years from blood collection to cancer diagnosis, body mass index, smoking intensity and duration, and serum total and high-density lipoprotein cholesterol did not alter the results. Participants with a higher metabolic score based on the discovery set had an elevated risk of prostate cancer-specific mortality in the replication set (fourth versus first quartile, HR=3.9, P-value for trend<0.0001).ConclusionsThe metabolic traits identified in this study, including for choline, glutamate, arachidonate, gamma-glutamyl amino acids, fibrinopeptides, and endocannabinoid and redox pathways and their composite risk score, corroborate our previous analysis of fatal prostate cancer and provide novel insights and potential leads regarding the molecular basis of prostate cancer progression and mortality.

Dataset Information

Digoxin and prostate cancer survival in the Finnish Randomized Study of Screening for Prostate Cancer.

Publications

Digoxin and prostate cancer survival in the Finnish Randomized Study of Screening for Prostate Cancer.

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