Association between antihypertensive drugs and oral cancer: a drug target Mendelian randomization study

Junfeng Guo; Rongxing Liu; Fangfang Sheng; Qiuxiang Wu; Rufu Xu; Haitao He; Gang Zhang; Junjie Huang; Zhe Zhang; Rong Zhang

doi:10.3389/fphar.2023.1294297

Association between antihypertensive drugs and oral cancer: a drug target Mendelian randomization study

Front Pharmacol. 2023 Nov 27:14:1294297. doi: 10.3389/fphar.2023.1294297. eCollection 2023.

Authors

Junfeng Guo^{1

2}, Rongxing Liu¹, Fangfang Sheng¹, Qiuxiang Wu¹, Rufu Xu¹, Haitao He³, Gang Zhang³, Junjie Huang³, Zhe Zhang¹, Rong Zhang¹

Affiliations

¹ Department of Pharmacy, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
² Department of Stomatology, The 970th Hospital of the Joint Logistics Support Force, Yantai, China.
³ Department of Stomatology, Xinqiao Hospital, Third Military Medical University, Chongqing, China.

Abstract

Background: Recent reports have suggested that antihypertensive drugs may play an oncogenic role in common cancers, but it is still uncertain whether this could influence the risk of oral cancer. Through two-sample Mendelian randomization (MR), we sought to assess the causal effect of antihypertensive drugs on oral cancer outcomes. Methods: To proxy the exposure of antihypertensive drugs, we utilized two genetic instruments, including expression quantitative trait loci of drug target genes and genetic variants within or around drug target genes related to blood pressure from genome-wide association studies. Inverse-variance-weighted MR (IVW-MR) and summary-data-based MR (SMR) were employed to compute the instrument effect estimates. Results: It was observed through IVW-MR analysis that there is a positive relationship between KCNH2 (target of beta-adrenoceptor blockers)-mediated blood pressure and oral cancer (odds ratio [OR] = 1.197, 95% confidence interval [CI] = 1.028-1.394). Similarly, SMR analysis demonstrated that a higher expression of KCNH2 (target of beta-adrenoceptor blockers) was linked to a greater risk of oral cancer (OR = 2.223, 95% CI = 1.094-4.516). Both analyses yielded no consistent evidence of other associations. Conclusion: This two-sample MR study proposed a latent causal association between KCNH2 (target of beta-adrenoceptor blockers) inhibition and diminished risk of oral cancer.

Keywords: Mendelian randomization; antihypertensive drugs; blood pressure; causal effect; oral cancer.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Chongqing Talent project (CQYC20210303411) and the Chongqing Key Specialty Construction Project of Clinical Pharmacy (Clinical Pharmacy of Cardiovascular Medicine).