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Subtype-Specific Causal Effects of Antidiabetic Drug Targets on Ovarian Cancer: Mendelian Randomization and

Enyu Tang1, Jia Zeng1, Xinlong Shi2

  • 1Department of Gynecology Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People's Republic of China.

International Journal of Women'S Health
|March 16, 2026
PubMed
Abstract

Insights

Antidiabetic drug targets show subtype-specific associations with ovarian cancer (OC) risk and survival. This suggests potential for repurposing these drugs to treat diverse OC subtypes, improving patient outcomes.

Area of Science:

  • Genetics
  • Oncology
  • Pharmacology

Background:

  • Ovarian cancer (OC) has high mortality and limited treatments, necessitating novel therapeutic targets for precision therapy.
  • Antidiabetic drug targets present a potential avenue for expanding OC treatment options across various subtypes.

Purpose of the Study:

  • To investigate the association between antidiabetic drug target genes and the risk/survival of different ovarian cancer (OC) subtypes.
  • To explore the potential of repurposing antidiabetic drugs for OC treatment based on genetic associations.

Main Methods:

  • Utilized integrated analysis of large-scale datasets (Ovarian Cancer Association Consortium, eQTLGen, GTEx).
  • Employed two-sample Mendelian randomization (MR), summary data-based MR, and colocalization analysis.
  • Validated findings using positive control, replication, MR-Egger, Bonferroni correction, and MR-PRESSO outlier tests.

Main Results:

  • Identified significant subtype-specific associations between antidiabetic drug targets and OC risk (e.g., AKR1A1 with low grade serous OC, HMGCR/KCNJ11 with clear cell OC).
  • Found associations for mucinous OC (ITGAL, AKR1B1) and endometrioid OC (AKR1A1, ITGAL).
  • Observed a link between DPP4 and high-grade serous OC survival.

Conclusions:

  • Demonstrated significant subtype-specific heterogeneity in genetic links between antidiabetic targets and OC.
  • These findings support a metabolic role in OC progression and suggest drug repurposing for tailored, subtype-specific therapies.
Keywords:
antidiabetic target genesgene expressionmendelian randomizationovarian cancer

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