ArticleFrontiers in pharmacology2026
Genetic insights revealed ADRB1 as potential target for clear cell renal cell carcinoma.
Article in Frontiers in pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Antihypertensive drug targets are associated with various cancers, but their relationship with clear cell renal cell carcinoma (CCRCC) risk remains unclear. Methods: Summary-data-based Mendelian randomization (SMR) and colocalization analyses were performed. Four antihypertensive drug targets (ACE, ADRB1, ADRB2, and SLC12A3) and CCRCC were included. Patients with CCRCC were identified from two large GWAS databases, including 752,817 and 315,137 individuals (Finnish cohorts), for the discovery and external validation analyses, respectively. Meta-analysis was conducted to integrate the results from both cohorts. Western blotting and prognostic analyses of tumor survival revealed the relationship between ADRB1 and CCRCC. Results: ADRB1 was associated with CCRCC risk in both the discovery and validation cohorts (odds ratio (OR): 1.097, per standard deviation unit (SD) change in antihypertensive drug target perturbation equivalent to 1 SD unit of decreased blood pressure; 95% confidence interval (95% CI): 1.063-1.132; P-value = 0.016) vs. OR: 1.284; 95% CI: 1.014-1.627; P-value = 0.013). ADRB2 was associated with CCRCC risk in discovery cohort (OR: 1.224; 95% CI: 1.045-1.433; P-value = 0.019). Integrated outcomes demonstrated that both ADRB1 (OR: 1.100; 95% CI: 1.066-1.135; P-value<0.0001) and ADRB2 (OR: 1.313; 95% CI: 1.137-1.517; P-value = 0.0002) were associated with CCRCC risk. Colocalization analyses indicated that ADRB1 (PP4 = 0.996) and ADRB2 (PP4 = 0.895) shared the same region of genetic variation with CCRCC. Furthermore, ADRB1 was highly expressed in CCRCC tumor tissues and was associated with poor tumor survival and prognosis. Conclusion: ADRB1 was associated with the risk of CCRCC, providing additional perspectives into potential treatment strategies for CCRCC.
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