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Causal relationship between hypertension and cancer: a two‑sample bidirectional Mendelian randomization study
Chenggong Zeng1,2,3, Juanhua Zhu4, Yan Mao1,2,3
1State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China.
Translational Cancer Research
|December 11, 2025
Summary
Hypertension may reduce the risk of gastric and colorectal cancers. This inverse association, identified through Mendelian randomization (MR), suggests potential benefits of blood pressure management in cancer prevention.
Area of Science:
- Genetics
- Epidemiology
- Oncology
Background:
- Observational studies show conflicting evidence on hypertension and cancer risk, possibly due to confounding factors.
- Reverse causality is a significant challenge in understanding the hypertension-cancer relationship.
Purpose of the Study:
- To investigate the causal relationship between hypertension and various cancer types using Mendelian randomization (MR).
- To explore potential mechanisms linking hypertension and cancer risk, including the role of antihypertensive medications.
Main Methods:
- Two-sample bidirectional MR analyses were performed using genetic variants for hypertension and 17 site-specific cancers.
- Genome-wide association study (GWAS) data from large cohorts were utilized.
- Inverse variance weighted (IVW) method was the primary analysis, with sensitivity analyses and pleiotropy assessments.
Main Results:
- Hypertension showed a causal association with decreased risk of gastric cancer (OR=0.615) and colorectal cancer (OR=0.708).
- Reverse MR indicated an inverse association between lymphoma and hypertension risk, and a positive association between thyroid cancer and hypertension.
- Antihypertensive drugs, including ACEIs/ARBs, beta-blockers, and CCBs, were inversely associated with gastric and colorectal cancer risk.
Conclusions:
- Genetic predisposition to hypertension is associated with a reduced risk of gastric and colorectal cancers.
- The observed inverse relationship may be mediated by biological pathways targeted by antihypertensive drugs.
- Further clinical research is warranted to explore these mechanistic links for cancer prevention strategies.
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