Adrenergic blockers and the risk for common solid cancers: a case–control study

Abstract

Laboratory studies have suggested that adrenergic blockers may inhibit the proliferation and migration of cancer cells, but epidemiological evidence of their effect on cancer incidence has proven inconsistent. We therefore conducted a case-control study using the Clinical Practice Research Datalink to assess the effect of adrenergic blockers on the incidence of prostate, lung, bowel and breast cancers. From among patients aged 18 years or older who contributed at least 2 years of prospectively gathered data between 1 January 1987 and 31 December 2012, we selected incident cases of relevant cancers and controls, frequency matched 10 : 1 by age. Logistic regression was used to adjust effect estimates for age, sex, smoking, alcohol use, and a number of potentially confounding comorbidities and coprescriptions. A total of 18 968 colorectal, 19 082 lung, 21 608 prostate and 29 109 breast cancers were identified. We found no evidence of a protective effect of adrenergic blockade in lung and prostate cancers and found a slightly increased risk for colorectal and breast cancers in users. This was largely explained by the effects of confounding in multivariate analyses, with final odds ratio estimates for lung, colorectal, breast and prostate cancers of 0.99 [95% confidence interval (0.96-1.04)], 1.14 (1.09-1.18), 1.10 (1.06-1.14), and 1.01 (0.98-1.05), respectively, for β-blocker exposure, and final odds ratio estimates for lung, colorectal and breast cancer of 1.03 (0.97-1.09), 1.13 (1.07-1.20), and 1.08 (1.00-1.17), respectively, for α-blocker exposure. We found no evidence to suggest that adrenergic blocker use prevents common cancers. Indeed, we found a slightly increased risk for colorectal and breast cancers, which may reflect residual confounding.

Association Between Antihypertensive Medication Use and Breast Cancer: A Systematic Review and Meta-Analysis

“…Our conclusion that BBs were associated with increased breast cancer risk was consistent with this highly influential and large studies ( Numbere et al, 2015 ; Chang et al, 2016 ; Zheng et al, 2021 ). The prospective study data minimizes the recall bias and in the study in question, some important confounders such as alcohol status, smoking status, BMI, medication and comorbidities, were adjusted.…”

“…A total of 842 potentially eligible studies were retrieved from the selected databases during the initial search. After removing duplicates and further screening the titles and abstracts, 26 studies on breast cancer risk ( Meier et al, 2000 ; Li et al, 2003 ; Gonzalez-Perez et al, 2004 ; Fryzek et al, 2006 ; Largent et al, 2006 ; Davis and Mirick, 2007 ; Van Der Knaap et al, 2008 ; Coogan et al, 2009 ; Largent et al, 2010 ; Huang et al, 2011 ; Hallas et al, 2012 ; Lee et al, 2012 ; Mackenzie et al, 2012 ; Biggar et al, 2013 ; Li et al, 2013 ; Saltzman et al, 2013 ; Devore et al, 2015 ; Numbere et al, 2015 ; Azoulay et al, 2016 ; Chang et al, 2016 ; Gomez-Acebo et al, 2016 ; Wilson et al, 2016 ; Brasky et al, 2017 ; Raebel et al, 2017 ; Busby et al, 2018b ; Zheng et al, 2021 ), and 30 studies on breast cancer prognosis ( Powe et al, 2010 ; Barron et al, 2011 ; Ganz et al, 2011 ; Melhem-Bertrandt et al, 2011 ; Shah et al, 2011 ; Şendur et al, 2012 ; Holmes et al, 2013a ; Holmes et al, 2013b ; Botteri et al, 2013 ; Cardwell et al, 2013 ; Chae et al, 2013 ; Sorensen et al, 2013 ; Boudreau et al, 2014 ; Cardwell et al, 2014 ; Sakellakis et al, 2014 ; Babacan et al, 2015 ; Chen et al, 2015 ; Springate et al, 2015 ; Cardwell et al, 2016 ; Choy et al, 2016 ; Chen et al, 2017 ; Spera et al, 2017 ; Busby et al, 2018a ; Musselman et al, 2018 ; Cui et al, 2019 ; Takada et al, 2019 ; Modi et al, 2...…”

Effects of Antihypertensive Drugs Use on Risk and Prognosis of Colorectal Cancer: A Meta-Analysis of 37 Observational Studies

“…Studies were retrieved by filtering titles and abstracts, and 39 studies were excluded after full text review, and reasons why studies were excluded were listed in Supplementary Table S4 . Ultimately, we included 37 studies for our meta-analysis, including 20 publications concerning cancer risk ( Pahor et al, 1996 ; Michels et al, 1998 ; Rosenberg et al, 1998 ; Tenenbaum et al, 2001 ; Beiderbeck-Noll et al, 2003 ; Boudreau et al, 2008 ; van der Knaap et al, 2008 ; Friedman et al, 2011 ; Hallas et al, 2012 ; Jansen et al, 2012 ; Wang et al, 2012 ; Mansouri et al, 2013 ; Makar et al, 2014 ; Chang et al, 2015 ; Lin et al, 2015 ; Numbere et al, 2015 ; Grimaldi-Bensouda et al, 2016 ; Dierssen-Sotos et al, 2017 ; Cheung et al, 2020 ; Brasky et al, 2021 ), 17 regarding cancer prognosis ( Sorensen et al, 2000 ; Hicks et al, 2013 ; Holmes et al, 2013 ; Cardwell et al, 2014 ; Jansen et al, 2014 ; Giampieri et al, 2015 ; Osumi et al, 2015 ; Morris et al, 2016 ; Jansen et al, 2017 ; Weberpals et al, 2017 ; Sud et al, 2018 ; Bowles et al, 2019 ; Cui et al, 2019 ; Fiala et al, 2019 ; Mafiana et al, 2019 ; Ozawa et al, 2019 ; Ahl et al, 2020 ). Of these 37 studies, 26 studies used cohort design, three studies used nested case-control design, and 8 studies used case-control design.…”

Agonist Effects of Propranolol on Non-Tumor Human Breast Cells

“…On the other hand, other studies conclude that the use of β-blockers has no effect on the prognosis or survival of patients with breast cancer [17,30]. Furthermore, other retrospective studies associated the use of β-blockers with an increased risk of breast cancer and recurrence rates [19]. All these works demonstrate inconsistencies related to the use of β-blockers and their specific role in the breast.…”

“…Preclinical studies have suggested that β-adrenergic antagonists can inhibit multiple cellular processes, including cell proliferation and metastases [16]. However, the evidence regarding the effect of β-blockers on the breast is so far contradictory, showing inconsistencies related to the use of β-blockers and their specific role [17][18][19][20]. The similarity of action found between agonists and antagonists can be explained by the fact that several β-adrenergic antagonists do not really act as pure antagonists [21].…”