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

被引：1

作者：

Zheng, Jie ^{[1
,2
,3
]}

Lu, Jieli ^{[1
,2
]}

Qi, Jiying ^{[1
,2
]}

Yang, Qian ^{[3
]}

Zhao, Huiling ^{[3
]}

Liu, Haoyu ^{[1
,2
]}

Chen, Zhihe ^{[1
,2
]}

Huang, Lanhui ^{[1
,2
]}

Ye, Youqiong ^{[4
,5
]}

Xu, Min ^{[1
,2
]}

Xu, Yu ^{[1
,2
]}

Wang, Tiange ^{[1
,2
]}

Li, Mian ^{[1
,2
]}

Zhao, Zhiyun ^{[1
,2
]}

Zheng, Ruizhi ^{[1
,2
]}

Wang, Shuangyuan ^{[1
,2
]}

Lin, Hong ^{[1
,2
]}

Hu, Chunyan ^{[1
,2
]}

Chui, Celine Sze Ling ^{[6
,7
,8
]}

Yeung, Shiu Lun Au ^{[7
]}

Luo, Shan ^{[3
,7
]}

Dimopoulou, Olympia ^{[3
,9
]}

Dixon, Padraig ^{[3
,10
]}

Harrison, Sean ^{[3
,10
]}

Liu, Yi ^{[3
]}

Robinson, Jamie ^{[3
]}

Yarmolinsky, James ^{[3
]}

Haycock, Philip ^{[3
]}

Yuan, Jinqiu ^{[12
,13
,14
,15
]}

Lewis, Sarah ^{[3
]}

Yuan, Zhongshang ^{[16
]}

Gaunt, Tom R. ^{[3
,11
,17
,18
]}

Smith, George Davey ^{[3
,11
,17
,18
]}

Ning, Guang ^{[1
,2
]}

Martin, Richard M. ^{[3
,7
,17
,18
]}

Cui, Bin ^{[1
,2
]}

Wang, Weiqing ^{[1
,2
]}

Bi, Yufang ^{[1
,2
]}

机构：

[1] Shanghai Jiao Tong Univ, Ruijin Hosp, Shanghai Inst Endocrine & Metab Dis, Dept Endocrine & Metab Dis,Sch Med, Shanghai, Peoples R China

[2] Shanghai Jiao Tong Univ, Ruijin Hosp, Shanghai Natl Clin Res Ctr Metab Dis, Natl Hlth Commiss PR China,Shanghai Digital Med In, Shanghai, Peoples R China

[3] Univ Bristol, Bristol Med Sch, MRC Integrat Epidemiol Unit IEU, Oakfield House, Bristol BS8 2BN, England

[4] Shanghai Jiao Tong Univ, Ruijin Hosp, Shanghai Inst Immunol, Ctr Immune Related Dis,Sch Med, Shanghai, Peoples R China

[5] Shanghai Jiao Tong Univ, Shanghai Inst Immunol, Dept Immunol & Microbiol, State Key Lab Oncogenes & Related Genes,Sch Med, Shanghai 200025, Peoples R China

[6] Univ Hong Kong, Li Ka Shing Fac Med, Sch Nursing, Hong Kong, Peoples R China

[7] Univ Hong Kong, Li Ka Shing Fac Med, Sch Publ Hlth, Hong Kong, Peoples R China

[8] Lab Data Discovery Hlth D24H, Hong Kong Sci Pk,Hong Kong Sci & Technol Pk, Hong Kong, Peoples R China

[9] Univ Bristol, Bristol Med Sch, Populat Hlth Sci, Bristol BS8 2PS, England

[10] Univ Oxford, Nuffield Dept Primary Care Hlth Sci, Oxford OX2 6GG, England

[11] Univ Bristol, Bristol Med Sch, Dept Populat Hlth Sci, Bristol BS8 2BN, England

[12] Sun Yat sen Univ, Affiliated Hosp 7, Clin Res Ctr, Shenzhen 518107, Guangdong, Peoples R China

[13] Sun Yat sen Univ, Affiliated Hosp 7, Ctr Digest Dis, Shenzhen 518107, Guangdong, Peoples R China

[14] Guangzhou Women & Children Med Ctr, Guangzhou 510623, Guangdong, Peoples R China

[15] Chinese Univ Hong Kong, JC Sch Publ Hlth & Primary Care, Div Epidemiol, Hong Kong, Peoples R China

[16] Shandong Univ, Cheeloo Coll Med, Sch Publ Hlth, Dept Biostat, Jinan, Peoples R China

[17] Univ Hosp Bristol & Weston NHS Fdn Trust, NIHR Biomed Res Ctr, Bristol, England

[18] Univ Bristol, Bristol, England

来源：

CELL REPORTS MEDICINE | 2024年 / 5卷 / 08期

基金：

中国国家自然科学基金; 英国医学研究理事会; 英国惠康基金;

关键词：

RISK; EPIDEMIOLOGY; ASSOCIATION; INSTRUMENTS; MEDICATION; UPDATE; ADULTS;

D O I：

10.1016/j.xcrm.2024.101688

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 HbA1c 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.

引用

页数：17

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