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Stress susceptibility, beta-blocker use and cancer survival
Örebro University, School of Medical Sciences.
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 [en]
stress resilience, β-blockers, primary cancer, survival analysis, overall mortality, cancer-specific mortality, register-based cohort study
National Category
General Practice
Identifiers
URN: urn:nbn:se:oru:diva-80720ISBN: 978-91-7529-338-7 (print)OAI: oai:DiVA.org:oru-80720DiVA, id: diva2:1415298
Public defence
2020-05-28, Örebro universitet, Campus USÖ, hörsal C1, Södra Grev Rosengatan 32, Örebro, 13:15 (English)
Opponent
Supervisors
Available from: 2020-03-18 Created: 2020-03-18 Last updated: 2020-05-15Bibliographically approved
List of papers
1. Stress resilience in late adolescence and survival among cancer patients: a Swedish register-based cohort study
Open this publication in new window or tab >>Stress resilience in late adolescence and survival among cancer patients: a Swedish register-based cohort study
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2019 (English)In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 28, no 2, p. 400-408Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Chronic stress has been suggested to play a role in cancer progression, but few studies have so far examined the potential influence of stress susceptibility. This national register-based cohort study utilizes a unique data source to investigate whether a stress resilience measure is associated with survival in cancer patients.

METHODS: The cohort includes 9,318 Swedish male cancer patients born during 1952-1956 who had their stress resilience evaluated at a semi-structured interview with a psychologist during mandatory conscription examination in late adolescence.

RESULTS: Over a median of 3 years of follow-up from cancer diagnosis, a total of 2,541 patients died (2,322 from cancer). Overall, low (23%) compared with high (25%) stress resilience was associated with increased mortality (adjusted hazard ratio estimated by Cox regression 1.45; 95% confidence interval 1.28-1.65), particularly among men with carcinomas of the oropharynx (2.62, 1.24-5.56), upper respiratory tract (4.64, 1.05-20.41), and prostate (2.20, 1.04-4.62), as well as with Hodgkin's lymphoma (3.52, 1.40-8.86). An association was evident both for cancer types associated with smoking (1.35, 1.10-1.66) and malignancies without an established smoking aetiology (1.32, 1.12-1.56). The association between low stress resilience and mortality could partly be explained by tumour stage, marital status, and psychiatric comorbidity at cancer diagnosis.

CONCLUSIONS: We observed an association between low stress resilience and mortality among men diagnosed with cancer, particularly, oropharyngeal cancer, upper respiratory tract cancers, prostate cancer and Hodgkin's lymphoma.

IMPACT: These results suggest that individual variation in stress resilience may influence survival among men with some cancer types.

Place, publisher, year, edition, pages
American Association for Cancer Research, 2019
National Category
Cancer and Oncology Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:oru:diva-69907 (URN)10.1158/1055-9965.EPI-18-0451 (DOI)000465321600019 ()30333220 (PubMedID)2-s2.0-85061062199 (Scopus ID)
Funder
Swedish Cancer Society, CAN 2013/650
Note

Funding Agency:

UK Economic and Social Research Council (ESRC)  RES-596-28-0001

Available from: 2018-11-06 Created: 2018-11-06 Last updated: 2020-05-05Bibliographically approved
2. Beta-Blocker Drug Use and Survival among Patients with Pancreatic Adenocarcinoma
Open this publication in new window or tab >>Beta-Blocker Drug Use and Survival among Patients with Pancreatic Adenocarcinoma
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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
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:oru:diva-58937 (URN)10.1158/0008-5472.CAN-17-0108 (DOI)000404718400028 ()28473530 (PubMedID)2-s2.0-85023745947 (Scopus ID)
Funder
Swedish Cancer Society, CAN 2013/650
Available from: 2017-08-21 Created: 2017-08-21 Last updated: 2020-05-05Bibliographically approved
3. Beta-blocker use and lung cancer mortality in a nationwide cohort study of patients with primary non-small cell lung cancer
Open this publication in new window or tab >>Beta-blocker use and lung cancer mortality in a nationwide cohort study of patients with primary non-small cell lung cancer
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2019 (English)In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 29, no 1, p. 119-126Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Beta-adrenergic receptor blockers have been associated with improved survival among patients with different types of malignancies, but available data for non-small cell lung cancer (NSCLC) patients is contradictory and limited to small hospital-based studies. We therefore aimed to investigate if β-blocker use at the time of cancer diagnosis is associated with lung cancer mortality in the largest general population-based cohort of patients with NSCLC to date.

PATIENTS AND METHODS: For this retrospectively defined nationwide cohort study, we used prospectively collected data from Swedish population and health registers. Through the Swedish Cancer Register, we identified 18,429 patients diagnosed with a primary NSCLC between 2006 and 2014 with follow-up to 2015. Cox regression was used to estimate the association between beta-blocker use at time of cancer diagnosis ascertained from the Prescribed Drug Register and cancer-specific mortality identified from the Cause of Death Register.

RESULTS: Over a median follow-up of 10.2 months, 14,994 patients died (including 13,398 from lung cancer). Compared with non-use, beta-blocker use (predominantly prevalent use, 93%) was not associated with lung cancer mortality [hazard ratio (95% confidence interval): 1.01 (0.97-1.06)]. However, the possibility that diverging associations for specific beta-blockers and some histopathological subtypes exist cannot be excluded.

CONCLUSION: In this nationwide cohort of NSCLC patients, beta-blocker use was not associated with lung cancer mortality when assessed in aggregate in the total cohort, but evidence for some beta-blockers is less conclusive.

IMPACT: Our results do not indicate that beta-blocker use at lung cancer diagnosis reduces the cancer-specific mortality rate in NSCLC patients.

Place, publisher, year, edition, pages
Prevention American Association for Cancer Research, 2019
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-77618 (URN)10.1158/1055-9965.EPI-19-0710 (DOI)000521285100015 ()31641010 (PubMedID)2-s2.0-85077915694 (Scopus ID)
Funder
Swedish Cancer Society, CAN 2013/650
Available from: 2019-10-25 Created: 2019-10-25 Last updated: 2020-05-05Bibliographically approved
4. Beta-adrenergic receptor blockers and liver cancer mortality in a national cohort of hepatocellular carcinoma patients
Open this publication in new window or tab >>Beta-adrenergic receptor blockers and liver cancer mortality in a national cohort of hepatocellular carcinoma patients
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(English)Manuscript (preprint) (Other academic)
National Category
General Practice
Identifiers
urn:nbn:se:oru:diva-81517 (URN)
Available from: 2020-05-05 Created: 2020-05-05 Last updated: 2020-05-05Bibliographically approved

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