Genetically proxied therapeutic effect of antihypertensive drug use, breast cancer, and ovarian cancer’s risk: a drug-target Mendelian randomization study
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 antihyper...
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BMC
2025-07-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-025-14350-2 |
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| author | Chunxiao Dang Ruohan Wang Yunzhen Shi Pengfei Liu Xiaofeng Wang Jinxing Liu Xiao Yu Dongxu Jin Qing Ma |
| author_facet | Chunxiao Dang Ruohan Wang Yunzhen Shi Pengfei Liu Xiaofeng Wang Jinxing Liu Xiao Yu Dongxu Jin Qing Ma |
| author_sort | Chunxiao Dang |
| collection | DOAJ |
| description | 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. |
| format | Article |
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| institution | DOAJ |
| issn | 1471-2407 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
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| series | BMC Cancer |
| spelling | doaj-art-f616a83d2e734e5f8b91b140b244cf8d2025-08-20T03:03:25ZengBMCBMC Cancer1471-24072025-07-012511910.1186/s12885-025-14350-2Genetically proxied therapeutic effect of antihypertensive drug use, breast cancer, and ovarian cancer’s risk: a drug-target Mendelian randomization studyChunxiao Dang0Ruohan Wang1Yunzhen Shi2Pengfei Liu3Xiaofeng Wang4Jinxing Liu5Xiao Yu6Dongxu Jin7Qing Ma8First Clinical Medical College, Shandong University of Traditional Chinese MedicineDongying People’s Hospital (Dongying Hospital of Shandong Provincial Hospital Group)Second Affiliated Hospital of Shandong University of Traditional Chinese MedicineFirst Clinical Medical College, Shandong University of Traditional Chinese MedicineDongying People’s Hospital (Dongying Hospital of Shandong Provincial Hospital Group)First Clinical Medical College, Shandong University of Traditional Chinese MedicineDepartment of Gynecology, Affiliated Hospital of Shandong University of Traditional Chinese MedicineDongying People’s Hospital (Dongying Hospital of Shandong Provincial Hospital Group)Department of Gynecology, Affiliated Hospital of Shandong University of Traditional Chinese MedicineAbstract 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.https://doi.org/10.1186/s12885-025-14350-2Antihypertensive drugsBreast cancerOvarian cancerMendelian randomizationDrug-Target MR |
| spellingShingle | Chunxiao Dang Ruohan Wang Yunzhen Shi Pengfei Liu Xiaofeng Wang Jinxing Liu Xiao Yu Dongxu Jin Qing Ma Genetically proxied therapeutic effect of antihypertensive drug use, breast cancer, and ovarian cancer’s risk: a drug-target Mendelian randomization study BMC Cancer Antihypertensive drugs Breast cancer Ovarian cancer Mendelian randomization Drug-Target MR |
| title | Genetically proxied therapeutic effect of antihypertensive drug use, breast cancer, and ovarian cancer’s risk: a drug-target Mendelian randomization study |
| title_full | Genetically proxied therapeutic effect of antihypertensive drug use, breast cancer, and ovarian cancer’s risk: a drug-target Mendelian randomization study |
| title_fullStr | Genetically proxied therapeutic effect of antihypertensive drug use, breast cancer, and ovarian cancer’s risk: a drug-target Mendelian randomization study |
| title_full_unstemmed | Genetically proxied therapeutic effect of antihypertensive drug use, breast cancer, and ovarian cancer’s risk: a drug-target Mendelian randomization study |
| title_short | Genetically proxied therapeutic effect of antihypertensive drug use, breast cancer, and ovarian cancer’s risk: a drug-target Mendelian randomization study |
| title_sort | genetically proxied therapeutic effect of antihypertensive drug use breast cancer and ovarian cancer s risk a drug target mendelian randomization study |
| topic | Antihypertensive drugs Breast cancer Ovarian cancer Mendelian randomization Drug-Target MR |
| url | https://doi.org/10.1186/s12885-025-14350-2 |
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