The effect of SGLT2 inhibition on prostate cancer: Mendelian randomization and observational analysis using electronic healthcare and cohort data.

IF 11.7 1区医学 Q1 CELL BIOLOGY Cell Reports Medicine Pub Date : 2024-08-20 DOI:10.1016/j.xcrm.2024.101688

Jie Zheng, Jieli Lu, Jiying Qi, Qian Yang, Huiling Zhao, Haoyu Liu, Zhihe Chen, Lanhui Huang, Youqiong Ye, Min Xu, Yu Xu, Tiange Wang, Mian Li, Zhiyun Zhao, Ruizhi Zheng, Shuangyuan Wang, Hong Lin, Chunyan Hu, Celine Sze Ling Chui, Shiu Lun Au Yeung, Shan Luo, Olympia Dimopoulou, Padraig Dixon, Sean Harrison, Yi Liu, Jamie Robinson, James Yarmolinsky, Philip Haycock, Jinqiu Yuan, Sarah Lewis, Zhongshang Yuan, Tom R Gaunt, George Davey Smith, Guang Ning, Richard M Martin, Bin Cui, Weiqing Wang, Yufang Bi

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Abstract

We evaluated the effect of sodium-glucose cotransporter 2 (SGLT2) inhibition on prostate cancer by evidence triangulation. Using Mendelian randomization, we found that genetically proxied SGLT2 inhibition reduced the risk of overall (odds ratio = 0.56, 95% confidence interval [CI] = 0.38 to 0.82; 79,148 prostate cancer cases and 61,106 controls), advanced, and early-onset prostate cancer. Using electronic healthcare data (n_SGLT2i = 24,155; n_DPP4i = 24,155), we found that the use of SGLT2 inhibitors was associated with a 23% reduced risk of prostate cancer (hazard ratio = 0.77, 95% CI = 0.61 to 0.99) in men with diabetes. Using data from two prospective cohorts (n_4C = 57,779; n_{UK_Biobank} = 165,430), we found little evidence to support the association of HbA_1c with prostate cancer, implying a non-glycemic effect of SGLT2 inhibition on prostate cancer. In summary, this study provides multiple layers of evidence to support the beneficial effect of SGLT2 inhibition on reducing prostate cancer risk. Future trials are warranted to investigate whether SGLT2 inhibitors can be recommended for prostate cancer prevention.

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SGLT2 抑制剂对前列腺癌的影响：利用电子医疗保健和队列数据进行孟德尔随机化和观察分析。

我们通过证据三角法评估了钠-葡萄糖共转运体 2（SGLT2）抑制对前列腺癌的影响。通过孟德尔随机法，我们发现基因代理的 SGLT2 抑制可降低总体（几率比 = 0.56，95% 置信区间 [CI] = 0.38 至 0.82；79,148 例前列腺癌病例和 61,106 例对照）、晚期和早发前列腺癌的发病风险。通过使用电子医疗保健数据（nSGLT2i = 24,155; nDPP4i = 24,155），我们发现使用 SGLT2 抑制剂与糖尿病男性前列腺癌风险降低 23% 相关（危险比 = 0.77，95% CI = 0.61 至 0.99）。利用两个前瞻性队列（n4C = 57,779; nUK_Biobank = 165,430）的数据，我们发现几乎没有证据支持 HbA1c 与前列腺癌的关联，这意味着 SGLT2 抑制剂对前列腺癌有非降糖作用。总之，本研究提供了多层证据，支持 SGLT2 抑制剂对降低前列腺癌风险的有益作用。未来有必要开展试验，研究是否可以推荐使用 SGLT2 抑制剂来预防前列腺癌。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Reports Medicine Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)

CiteScore

15.00

自引率

1.40%

发文量

231

审稿时长

40 days

期刊介绍： Cell Reports Medicine is an esteemed open-access journal by Cell Press that publishes groundbreaking research in translational and clinical biomedical sciences, influencing human health and medicine. Our journal ensures wide visibility and accessibility, reaching scientists and clinicians across various medical disciplines. We publish original research that spans from intriguing human biology concepts to all aspects of clinical work. We encourage submissions that introduce innovative ideas, forging new paths in clinical research and practice. We also welcome studies that provide vital information, enhancing our understanding of current standards of care in diagnosis, treatment, and prognosis. This encompasses translational studies, clinical trials (including long-term follow-ups), genomics, biomarker discovery, and technological advancements that contribute to diagnostics, treatment, and healthcare. Additionally, studies based on vertebrate model organisms are within the scope of the journal, as long as they directly relate to human health and disease.