Sustained Propranolol Use and Site-Specific All-Cause Mortality after Cancer Diagnosis: A Nationwide Taiwan Cohort Study
- 1Department of Neurosurgery, China Medical University Hospital, Taichung, Taiwan
- 2Neuroscience and Brain Disease Center, China Medical University, Taichung, Taiwan
- 3Sleep Medicine Center, China Medical University Hospital, Taichung, Taiwan
Abstract
Objectives: Drug repurposing offers a low-cost route to expanding cancer therapeutics. β-Adrenergic signalling links physiological stress to tumour progression, and propranolol, a non-selective β-blocker, interrupts this pathway upstream. Existing evidence is drawn predominantly from Western, single-cancer studies, and a comprehensive evaluation of survival across the cancer spectrum within a universal-coverage East Asian population has been lacking. Methods: In this nationwide retrospective cohort study using Taiwan’s National Health Insurance Research Database, patients with incident cancer (2010–2020) who received propranolol for at least six consecutive months after diagnosis were compared with non-users frequency-matched 1:4 by sex, age, and index year, yielding 11,500 patients (2300 users; 9200 non-users). All-cause mortality was analysed using Cox proportional hazards regression adjusted for age, sex, and area of residence, with a delayed index-date assignment for non-users intended to reduce temporal imbalance between cancer diagnosis and cohort entry. Pre-specified sensitivity analyses comprised alternative exposure-duration thresholds, propensity score matching, and E-value calculation; site-specific analyses applied false discovery rate control. Results: Over a median follow-up of 4.9 years, propranolol use was associated with lower all-cause mortality (adjusted hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.80–0.94), corresponding to 6.7 fewer deaths per 1000 person-years. The E-values for the primary adjusted HR and its upper 95% confidence limit were 1.56 and 1.32, respectively. Estimates across alternative exposure-duration thresholds ranged from 0.90 at three months to 0.83 at twelve months. The association was more evident among men and patients aged ≥ 60 years. Among pre-specified grouped categories, lower mortality was associated with propranolol use in genitourinary (HR 0.50, 95% CI 0.32–0.77) and digestive (HR 0.69, 95% CI 0.56–0.85) system cancers, whereas estimates for lung and liver cancer were near unity; individual cancer-site estimates were exploratory and non-significant after correction. Conclusion: In this nationwide East Asian cohort, sustained propranolol use was associated with lower all-cause mortality, most evident in genitourinary and digestive system cancers. These associations are hypothesis-generating rather than causal, given the observational design and unmeasured confounders including cancer stage and treatment, and support prioritising these categories for prospective evaluation of propranolol as a candidate for oncological repurposing. Because the exposure definition required survival to completion of a six-month treatment window, residual immortal time and selection bias cannot be excluded and the magnitude of the association may be overstated.
Related
- Behavior changes after lung cancer diagnosis and all-cause mortality in a nationwide cohort
- Sex-specific association between body mass index and mortality after heart transplantation: A nationwide KOTRY Cohort Study1
- Pre-Diagnosis Metabolic Health-Related Dietary Index and Prostate Cancer–Specific Mortality
- Cause-specific mortality attributable to summer heat in Italy, 2004-2023: a nationwide Bayesian spatiotemporal study
- Long-Term Mortality and Causes of Death After Kidney and Liver Transplantation: A Nationwide Population-Based Cohort Study in South Korea
BibTeX
@article{chen2026sustained,
title = {{Sustained Propranolol Use and Site-Specific All-Cause Mortality after Cancer Diagnosis: A Nationwide Taiwan Cohort Study}},
author = {Paul J. Chen and Jung-Ju Lin and Wei-Lin Hsu and Der-Cherng Chen and Yu-Hsiang Lin and Chien-Tung Yang and Chao-Hsuan Chen and Yu-Chung Juan and XianXiu Chen},
journal = {Oncology Research},
year = {2026},
month = oct,
doi = {10.32604/or.2026.086291},
url = {https://doi.org/10.32604/or.2026.086291},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Sustained Propranolol Use and Site-Specific All-Cause Mortality after Cancer Diagnosis: A Nationwide Taiwan Cohort Study
AU - Paul J. Chen
AU - Jung-Ju Lin
AU - Wei-Lin Hsu
AU - Der-Cherng Chen
AU - Yu-Hsiang Lin
AU - Chien-Tung Yang
AU - Chao-Hsuan Chen
AU - Yu-Chung Juan
AU - XianXiu Chen
PY - 2026
DA - 2026/10/28
JO - Oncology Research
DO - 10.32604/or.2026.086291
UR - https://doi.org/10.32604/or.2026.086291
AB - Objectives: Drug repurposing offers a low-cost route to expanding cancer therapeutics. β-Adrenergic signalling links physiological stress to tumour progression, and propranolol, a non-selective β-blocker, interrupts this pathway upstream. Existing evidence is drawn predominantly from Western, single-cancer studies, and a comprehensive evaluation of survival across the cancer spectrum within a universal-coverage East Asian population has been lacking. Methods: In this nationwide retrospective cohort study using Taiwan’s National Health Insurance Research Database, patients with incident cancer (2010–2020) who received propranolol for at least six consecutive months after diagnosis were compared with non-users frequency-matched 1:4 by sex, age, and index year, yielding 11,500 patients (2300 users; 9200 non-users). All-cause mortality was analysed using Cox proportional hazards regression adjusted for age, sex, and area of residence, with a delayed index-date assignment for non-users intended to reduce temporal imbalance between cancer diagnosis and cohort entry. Pre-specified sensitivity analyses comprised alternative exposure-duration thresholds, propensity score matching, and E-value calculation; site-specific analyses applied false discovery rate control. Results: Over a median follow-up of 4.9 years, propranolol use was associated with lower all-cause mortality (adjusted hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.80–0.94), corresponding to 6.7 fewer deaths per 1000 person-years. The E-values for the primary adjusted HR and its upper 95% confidence limit were 1.56 and 1.32, respectively. Estimates across alternative exposure-duration thresholds ranged from 0.90 at three months to 0.83 at twelve months. The association was more evident among men and patients aged ≥ 60 years. Among pre-specified grouped categories, lower mortality was associated with propranolol use in genitourinary (HR 0.50, 95% CI 0.32–0.77) and digestive (HR 0.69, 95% CI 0.56–0.85) system cancers, whereas estimates for lung and liver cancer were near unity; individual cancer-site estimates were exploratory and non-significant after correction. Conclusion: In this nationwide East Asian cohort, sustained propranolol use was associated with lower all-cause mortality, most evident in genitourinary and digestive system cancers. These associations are hypothesis-generating rather than causal, given the observational design and unmeasured confounders including cancer stage and treatment, and support prioritising these categories for prospective evaluation of propranolol as a candidate for oncological repurposing. Because the exposure definition required survival to completion of a six-month treatment window, residual immortal time and selection bias cannot be excluded and the magnitude of the association may be overstated.
SN - 0965-0407
SN - 1555-3906
ER -