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Beta-Blocker Drug Use and Survival among Patients with Pancreatic Adenocarcinoma
Örebro University, School of Medical Sciences. (Clinical Epidemiology and Biostatistics)
Örebro University, School of Medical Sciences. Clinical Epidemiology Unit, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, United Kingdom. (Clinical Epidemiology and Biostatistics)ORCID iD: 0000-0001-6328-5494
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Department of Cardiology, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
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2017 (English)In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 77, no 13, p. 3700-3707Article in journal (Refereed) Published
Abstract [en]

Preclinical studies have suggested that beta-adrenergic signaling is involved in pancreatic cancer progression. Prompted by such studies, we investigated an association between beta-blocker drug use with improved cancer-specific survival in a large, general population-based cohort of patients with pancreatic ductal adenocarcinoma (PDAC). All patients diagnosed with a first primary PDAC in Sweden between 2006 and 2009 were identified through the Swedish Cancer Register (n = 2,394). We obtained information about use of beta-blockers and other medications through linkage with the national Prescribed Drug Register. Cancer-specific mortality was assessed using the Swedish Cause of Death Register. We used multivariable Cox regression adjusted for sociodemographic factors, tumor characteristics, comorbidity score, and other medications to estimate HRs and 95% confidence intervals (CI) for cancer-specific mortality associated with beta-blocker use during the 90-day period before cancer diagnosis. A total of 2,054 (86%) died, with pancreatic cancer recorded as the underlying cause of death during a maximum of 5-year follow-up (median 5 months). Patients who used beta-blockers (n = 522) had a lower cancer-specific mortality rate than nonusers (adjusted HR, 0.79; 95% CI, 0.70-0.90; P < 0.001). This observed rate reduction was more pronounced among patients with localized disease at diagnosis (n = 517; adjusted HR, 0.60; 95% CI, 0.43-0.83; P = 0.002), especially for users with higher daily doses (HR, 0.54; 95% CI, 0.35-0.83; P = 0.005). No clear rate differences were observed by beta-blocker receptor selectivity. Our results support the concept that beta-blocker drugs may improve the survival of PDAC patients, particularly among those with localized disease.

Place, publisher, year, edition, pages
American Association for Cancer Research Inc. , 2017. Vol. 77, no 13, p. 3700-3707
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
URN: urn:nbn:se:oru:diva-58937DOI: 10.1158/0008-5472.CAN-17-0108ISI: 000404718400028PubMedID: 28473530Scopus ID: 2-s2.0-85023745947OAI: oai:DiVA.org:oru-58937DiVA, id: diva2:1134629
Funder
Swedish Cancer Society, CAN 2013/650Available from: 2017-08-21 Created: 2017-08-21 Last updated: 2020-06-17Bibliographically approved
In thesis
1. Stress susceptibility, beta-blocker use and cancer survival
Open this publication in new window or tab >>Stress susceptibility, beta-blocker use and cancer survival
2020 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Accumulating evidence suggests that chronic stress may influence tumour biology through activation of neuroendocrine pathways and thus impair survival. However, measuring stressful exposures and their influence on health is challenging, partly due to substantial inter-individual variation in stress susceptibility. The thesis aimed to explore whether stress resilience and use of β-adrenergic receptor blockers, which are implicated in regulation of neuroendocrine stress response pathways, are linked to survival after a primary cancer diagnosis using data from Swedish national registers. In a cohort of male cancer patients born during 1952-1956 who had their stress resilience assessed during a mandatory conscription examination in late adolescence, low compared with high stress resilience was associated with a higher overall mortality rate. Statistically significant reductions in survival were observed among men with carcinomas of the oropharynx, prostate, upper respiratory tract, and Hodgkin’s lymphoma. In a cohort of patients diagnosed with pancreatic adenocarcinoma during 2006-2009, β-blocker users had a lower pancreatic cancer mortality rate than non-users, particularly among patients without distant metastases at diagnosis. In a cohort of patients diagnosed with non-small cell lung cancer during 2006-2014, there was no clear association between β-blocker use and lung cancer survival, but we cannot exclude the possibility of associations in some sub-groups defined by histology, stage and β-blocker types. In a cohort of patients diagnosed with hepatocellular carcinoma during 2006-2014, β-blocker use was associated with lower liver cancer mortality, particularly among patients with localised disease. A higher-magnitude inverse association was observed for non-selective β-blocker use. In conclusion, greater stress resilience and β-blocker use are associated with improved survival among patients with some cancer types, and this may be explained by a variety of pathways.

Place, publisher, year, edition, pages
Örebro: Örebro University, 2020. p. 101
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 212
Keywords
Stress resilience, β-blockers, primary cancer, survival analysis, overall mortality, cancer-specific mortality, register-based cohort study
National Category
General Practice
Identifiers
urn:nbn:se:oru:diva-80720 (URN)978-91-7529-338-7 (ISBN)
Public defence
2020-05-28, Örebro universitet, Campus USÖ, hörsal C2, Södra Grev Rosengatan 32, Örebro, 13:15 (English)
Opponent
Supervisors
Available from: 2020-03-18 Created: 2020-03-18 Last updated: 2020-06-17Bibliographically approved

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Udumyan, RuzanMontgomery, ScottFall, Katja

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