Genetic proxies for calcium channel blockers and cancer: a Mendelian randomization study

Fan, Bohan; Schooling, CM; Zhao, Jie

doi:10.1038/s41371-023-00835-9

Cited by 5 publications

(2 citation statements)

References 43 publications

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“…Retrospective studies found no effect of CCB intake on RFS, CSS and OSS in UCB patients [14,17,18]. Interestingly, a recent study examining the associations of genetic proxies for CCBs with the risk for 17 site-specific cancers, including bladder cancer, found no correlation for any kind of cancer, thereby supporting the long-term safety profile of CCBs [39].…”

Section: Discussionmentioning

confidence: 98%

The Characterization of Non-oncologic Chronic Drug Therapy in Bladder Cancer Patients and the Impact on Recurrence-Free and Cancer-Specific Survival: A Prospective Study

Strobach,

Haimerl,

Mannell

et al. 2023

JCM

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We aimed to characterize non-oncologic chronic drug therapy of bladder cancer (BC) patients and evaluate a possible impact on recurrence-free (RFS) and cancer-specific survival (CSS). Patients with a first diagnosis (FD) of BC or radical cystectomy (RC) were included in a prospective, monocentric, observational study. Drugs and medical data was assessed at start and three-monthly for 24 months. Drugs were classified by anatomical-therapeutic-chemical code (ATC). Endpoints for outcome analysis were RFS and CSS in univariate (Kaplan–Meier curves and log-rank test, Cox regression for Hazard Ratio (HR)) and multivariate (Cox regression models) analyses. Of 113 patients, 52 had FD and 78 RC. Median age was 74 and 72 years, 83% and 82% were male. Drugs of 114 ATC classes were taken by 48 (92%) FD patients (median number 4.5/IQR 2–7.5) and 73 (94%) of RC patients (median 5/IQR 2–9). In univariate analysis (log-rank test (p)/Cox regression (HR, 95% CI, p)), polypharmacy (p = 0.036/HR = 2.83, 95% CI = 1.02–7.90, p = 0.047), calcium channel blockers (p = 0.046/HR = 2.47, 95% CI = 0.97–6.27, p = 0.057) and proton pump inhibitors (p = 0.015/HR = 3.16, 95% CI = 1.18–8.41, p = 0.022) had a significant negative impact on RFS in RC patients, statins (p = 0.025/HR = 0.14, 95% CI = 0.02–1.06, p = 0.057) a positive effect on RFS in FD patients, angiotensin-converting enzyme inhibitors (p = 0.008/HR = 10.74, 95% CI = 1.20–96.17, p = 0.034) and magnesium (p = 0.042/HR = 5.28, 95% CI = 0.88–31.59, p = 0.067) a negative impact on CSS in FD patients. In multivariate analysis, the only significant drug effects were the negative impact of angiotensin-converting enzyme inhibitors (HR = 15.20, 95% CI = 1.30–177.67, p = 0.030) and magnesium (HR = 22.87, 95% CI = 1.57–333.81), p = 0.022) on CSS in FD patients, and the positive impact of statins (HR = 0.12, 95% CI = 0.01–0.97, p = 0.047) on RFS in FD patients. Impact of non-oncologic drugs on RFS and CSS was small in this prospective study. Thus, appropriate treatment of comorbidities is encouraged.

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Section: Discussionmentioning

confidence: 98%

The Characterization of Non-oncologic Chronic Drug Therapy in Bladder Cancer Patients and the Impact on Recurrence-Free and Cancer-Specific Survival: A Prospective Study

Strobach,

Haimerl,

Mannell

et al. 2023

JCM

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“…However, recent studies have indicated no association between genetic proxies for CCB or other antihypertensives and breast cancer through Mendelian randomisation study design. 61 62 …”

Section: Discussionmentioning

confidence: 99%

Association between long-term use of calcium channel blockers (CCB) and the risk of breast cancer: a retrospective longitudinal observational study protocol

Ho,

Ha,

Youens

et al. 2024

BMJ Open

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IntroductionCalcium channel blockers (CCB), a commonly prescribed antihypertensive (AHT) medicine, may be associated with increased risk of breast cancer. The proposed study aims to examine whether long-term CCB use is associated with the development of breast cancer and to characterise the dose–response nature of any identified association, to inform future hypertension management.Methods and analysisThe study will use data from 2 of Australia’s largest cohort studies; the Australian Longitudinal Study on Women’s Health, and the 45 and Up Study, combined with the Rotterdam Study. Eligible women will be those with diagnosed hypertension, no history of breast cancer and no prior CCB use at start of follow-up (2004–2009). Cumulative dose-duration exposure to CCB and other AHT medicines will be captured at the earliest date of: the outcome (a diagnosis of invasive breast cancer); a competing risk event (eg, bilateral mastectomy without a diagnosis of breast cancer, death prior to any diagnosis of breast cancer) or end of follow-up (censoring event). Fine and Gray competing risks regression will be used to assess the association between CCB use and development of breast cancer using a generalised propensity score to adjust for baseline covariates. Time-varying covariates related to interaction with health services will also be included in the model. Data will be harmonised across cohorts to achieve identical protocols and a two-step random effects individual patient-level meta-analysis will be used.Ethics and disseminationEthical approval was obtained from the following Human research Ethics Committees: Curtin University (ref No. HRE2022-0335), NSW Population and Health Services Research Ethics Committee (2022/ETH01392/2022.31), ACT Research Ethics and Governance Office approval under National Mutual Acceptance for multijurisdictional data linkage research (2022.STE.00208). Results of the proposed study will be published in high-impact journals and presented at key scientific meetings.Trial registration numberNCT05972785.

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Common pitfalls in drug target Mendelian randomization and how to avoid them

Gill,

Dib,

Cronjé

et al. 2024

BMC Med

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Background Drug target Mendelian randomization describes the use of genetic variants as instrumental variables for studying the effects of pharmacological agents. The paradigm can be used to inform on all aspects of drug development and has become increasingly popular over the last decade, particularly given the time- and cost-efficiency with which it can be performed even before commencing clinical studies. Main body In this review, we describe the recent emergence of drug target Mendelian randomization, its common pitfalls, how best to address them, as well as potential future directions. Throughout, we offer advice based on our experiences on how to approach these types of studies, which we hope will be useful for both practitioners and those translating the findings from such work. Conclusions Drug target Mendelian randomization is nuanced and requires a combination of biological, statistical, genetic, epidemiological, clinical, and pharmaceutical expertise to be utilized to its full potential. Unfortunately, these skillsets are relatively infrequently combined in any given study.

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Genetic proxies for calcium channel blockers and cancer: a Mendelian randomization study

Cited by 5 publications

References 43 publications

The Characterization of Non-oncologic Chronic Drug Therapy in Bladder Cancer Patients and the Impact on Recurrence-Free and Cancer-Specific Survival: A Prospective Study

The Characterization of Non-oncologic Chronic Drug Therapy in Bladder Cancer Patients and the Impact on Recurrence-Free and Cancer-Specific Survival: A Prospective Study

Association between long-term use of calcium channel blockers (CCB) and the risk of breast cancer: a retrospective longitudinal observational study protocol

Common pitfalls in drug target Mendelian randomization and how to avoid them

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