Dang Chunxiao, Wang Ruohan, Shi Yunzhen, Liu Pengfei, Wang Xiaofeng, Liu Jinxing, Yu Xiao, Jin Dongxu, Ma Qing
First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China.
Dongying People's Hospital (Dongying Hospital of Shandong Provincial Hospital Group), South Road No.317, Dongying, Shandong, 257091, China.
BMC Cancer. 2025 Jul 1;25(1):1125. doi: 10.1186/s12885-025-14350-2.
Observational studies have explored the association between antihypertensive drugs and the risk of breast cancer (BC) and ovarian cancer (OC). However, some controversy persists.
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.
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.
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) and subset (B) (OR = 1.000, 95% CI: 1.000-1.001, P = 6.726 × 10) 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), 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.
Our study provides genetic evidence that CCBs increase the risk of OC, offering insight into the potential risks of pharmacological treatment with CCBs.
观察性研究探讨了抗高血压药物与乳腺癌（BC）和卵巢癌（OC）风险之间的关联。然而，仍存在一些争议。
我们的研究旨在使用两样本孟德尔随机化（MR）分析来研究抗高血压药物的遗传代理与乳腺癌和卵巢癌之间的因果关系。
主要使用逆方差加权（IVW）方法进行分析，并进行异质性和水平多效性检验以及敏感性分析，以评估结果的稳健性和因果关系的强度。
以Bonferroni校正的P值作为检验因果关系的阈值（P < 0.0025），在子集（A）中以收缩压作为生物标志物的MR分析（OR = 1.059，95% CI：1.024 - 1.096，P = 9.581×10）和子集（B）（OR = 1.000，95% CI：1.000 - 1.001，P = 6.726×10）均发现，基因预测的钙通道阻滞剂（CCB）会增加卵巢癌风险。在以舒张压作为生物标志物的MR分析中，仅在子集（B）中得到相同结果（OR = 1.001，95% CI：1.000 - 1.001，P = 3.465×10），而子集（A）显示CCB与卵巢癌发生风险之间存在提示性关联（OR = 1.088，95% CI：1.027 - 1.153，P = 0.004）。未检测到异质性或水平多效性，也未发现其他抗高血压药物与乳腺癌或卵巢癌之间存在关联的证据。
我们的研究提供了遗传证据，表明CCB会增加OC风险，为CCB药物治疗的潜在风险提供了见解。
