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. 2025 Jul 1;25(1):1125.
doi: 10.1186/s12885-025-14350-2.

Genetically proxied therapeutic effect of antihypertensive drug use, breast cancer, and ovarian cancer's risk: a drug-target Mendelian randomization study

Chunxiao Dang #  1 , Ruohan Wang #  2 , Yunzhen Shi  3 , Pengfei Liu  1 , Xiaofeng Wang  2 , Jinxing Liu  1 , Xiao Yu  4 , Dongxu Jin  5 , Qing Ma  6
Affiliations

Genetically proxied therapeutic effect of antihypertensive drug use, breast cancer, and ovarian cancer's risk: a drug-target Mendelian randomization study

Chunxiao Dang et al. BMC Cancer. .

Abstract

Background: Observational studies have explored the association between antihypertensive drugs and the risk of breast cancer (BC) and ovarian cancer (OC). However, some controversy persists.

Objective: Our study aims to investigate the causal relationship between genetic proxies for antihypertensive drugs and breast and ovarian cancers using two-sample Mendelian randomization (MR) analysis.

Methods: Analyses were primarily conducted using the inverse variance weighted (IVW) method, with heterogeneity and horizontal pleiotropy tests, as well as sensitivity analysis, to assess the robustness of the results and the strength of the causal relationship.

Results: Using the Bonferroni-corrected P-value as the threshold for testing causality (P < 0.0025), the MR analysis of systolic blood pressure as a biomarker in subset (A) (OR = 1.059, 95% CI: 1.024-1.096, P = 9.581 × 10- 4) and subset (B) (OR = 1.000, 95% CI: 1.000-1.001, P = 6.726 × 10- 4) both found that genetically predicted calcium channel blockers (CCBs) increased the risk of ovarian cancer. The same result was found only in subset (B) in the MR analysis of diastolic blood pressure as a biomarker (OR = 1.001, 95% CI: 1.000-1.001, P = 3.465 × 10- 4), while subset (A) showed a suggestive association between CCBs and the risk of ovarian cancer development (OR = 1.088, 95% CI: 1.027-1.153, P = 0.004). Neither heterogeneity nor horizontal pleiotropy was detected, and no evidence of an association between other antihypertensive drugs and breast or ovarian cancer was found.

Conclusions: Our study provides genetic evidence that CCBs increase the risk of OC, offering insight into the potential risks of pharmacological treatment with CCBs.

Keywords: Antihypertensive drugs; Breast cancer; Drug-Target MR; Mendelian randomization; Ovarian cancer.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Instrumental variable screening flow chart for MR Analysis
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