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Antihypertensive Drug Target Genes and Epithelial Ovarian Cancer Risk: A Two-Sample Mendelian Randomization Study

Jing Li1, Yali Feng1, Yuhong Shang1

  • 1Department of Obstetrics and Gynecology, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, People's Republic of China.

International Journal of Women'S Health
|March 30, 2026
PubMed
Abstract

Insights

Calcium channel blockers (CCBs) may lower epithelial ovarian cancer (EOC) risk by influencing CACNA2D3 gene expression. This Mendelian randomization study suggests a protective effect, warranting further investigation.

Area of Science:

  • Genetics
  • Oncology
  • Pharmacology

Background:

  • Inconsistent findings exist regarding the link between antihypertensive drugs and epithelial ovarian cancer (EOC) risk.
  • Mendelian randomization (MR) offers a method to investigate potential causal relationships using genetic proxies.

Purpose of the Study:

  • To investigate the relationship between antihypertensive drug target gene expression and EOC risk using a two-sample MR approach.
  • To utilize gene expression quantitative trait loci (eQTLs) as genetic instruments for antihypertensive drug action.

Main Methods:

  • Identified genetic instruments for antihypertensive medication target genes via blood eQTLs.
  • Obtained summary statistics for overall EOC and high-grade serous ovarian cancer (HGSOC) from GWAS datasets.
  • Employed the inverse variance weighted (IVW) method and conducted sensitivity analyses, applying Bonferroni Corrections for multiple testing.

Main Results:

  • Genetically proxied CACNA2D3 expression, a target of calcium channel blockers (CCBs), was associated with reduced risk of overall EOC and HGSOC (P < 7.2 x 10-5).
  • Suggestive associations were observed between SLC12A3 and overall EOC risk (P = 0.011), and between AHR, TNNC1 and HGSOC risk (P < 0.05).
  • No evidence of horizontal pleiotropy was detected for these associations.

Conclusions:

  • Genetically proxied CACNA2D3 expression may have a protective effect on EOC risk, potentially reflecting the benefits of CCBs.
  • Further validation studies are necessary to confirm these findings and their clinical implications.
Keywords:
Mendelian randomizationantihypertensive medicationepithelial ovarian cancerexpression quantitative trait loci

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