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A drug-target Mendelian randomization framework was applied to assess associations between genetically proxied lipid-lowering targets and cancer risks. Using cis-expression instruments from GTEx v8 and lipid trait data from UK Biobank, causal effects were estimated with IVW and supported by colocalization and sensitivity analyses, with external validation using GLGC summary statistics.",{"@graph":69,"@context":126},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/the-role-of-lipid-lowering-drugs-in-urologic-and-male-reproductive-cancers-a-mendelian-randomization-study/363625/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/the-role-of-lipid-lowering-drugs-in-urologic-and-male-reproductive-cancers-a-mendelian-randomization-study/363625.png","ImageObject",300,407,{"name":92,"@type":93},"Kurz","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118,122],{"name":109,"@type":110,"acceptedAnswer":111},"What was the study’s main objective?","Question",{"text":112,"@type":113},"To evaluate whether lipid-lowering drug targets have causal, heterogeneous associations with urologic and male reproductive cancer risks using a drug-target Mendelian randomization design.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which datasets were used to derive genetic instruments and outcomes?",{"text":117,"@type":113},"Cis-expression quantitative trait loci from GTEx v8 were used as instruments, lipid associations were taken from UK Biobank, and cancer outcomes were obtained from FinnGen, with validation using GLGC lipid summary statistics.",{"name":119,"@type":110,"acceptedAnswer":120},"What key causal associations were found across cancer types?",{"text":121,"@type":113},"Genetically proxied inhibition of HMGCR and NPC1L1 related to lower prostate cancer risk, while PCSK9 showed higher risk for bladder cancer; ANGPTL3 inhibition and reduced LPL activity were linked to increased risks of selected urologic cancers.",{"name":123,"@type":110,"acceptedAnswer":124},"How did the authors test the robustness of causal estimates?",{"text":125,"@type":113},"They used inverse-variance weighted estimation and additional sensitivity analyses addressing pleiotropy, heterogeneity, and robustness, including leave-one-out analyses, and confirmed key findings in external validation.","https://schema.org",{"og:url":83,"og:type":128,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":130,"canonical":83},"index,follow",{"doc_id":132,"site_id":62},363625,1790240356,{"code":4,"msg":5,"data":135},{"doc_id":132,"user_id":136,"nickname":92,"user_avatar":137,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":138,"file_id":139,"file_url":140,"file_type":141,"file_size":142,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":143,"language":144,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":145,"faqs":146,"seo_title":147,"seo_description":67,"update_tm":148,"read_time":149},2336478945635,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","Original Article  \nThe role of lipid-lowering drugs in urologic and male reproductive cancers: a Mendelian randomization study  \nYou-Tu Lin1,2\\#^, Jia-Quan Zhou1\\#, Cong-Jie Xu1, Li-Song Xiao1, Lian-Yang Weng1, Ying-Guang Li2, Yang Wang1  \n1Department of Urology, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, China; 2Department of General Surgery, Danzhou Third People’s Hospital, Danzhou, China  \nContributions: (I) Conception and design: YT Lin, JQ Zhou, YG Li, Y Wang; (II) Administrative support: Y Wang; (III) Provision of study materials or patients: YT Lin, Y Wang; (IV) Collection and assembly of data: CJ Xu, LS Xiao; (V) Data analysis and interpretation: CJ Xu, LS Xiao, LY Weng;  \n(VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.  \n\\#These authors contributed equally to this work as co-first authors.  \nCorrespondence to: Yang Wang, MD, PhD. Department of Urology, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), No. 19 Xiuhua Road, Xiuying District, Haikou 570311, [China. Email: Wysci2008@126.com](China. Email: Wysci2008@126.com); Ying-Guang Li, MB. Department of General Surgery, Danzhou Third People’s Hospital, No. 181 Jiefang North Road, Danzhou 571700, China. Email: [2307191732@qq.com](2307191732@qq.com).  \nBackground: Urologic and male reproductive system tumors are common in older men and frequently coexist with cardiovascular and metabolic disorders, suggesting potential shared biological pathways.  \nAlthough lipid-lowering therapies are widely used for cardiovascular prevention, their long-term associations with these cancers remain incompletely understood. We therefore applied a drug-target Mendelian randomization (MR) framework to evaluate the associations between genetically proxied lipid-lowering  \ntargets and the risks ofurologic and male reproductive cancers.  \nMethods: We performed a drug-target MR analysis using significant cis-expression quantitative trait loci for lipid-lowering drug target genes from the Genotype-Tissue Expression (GTEx v8) dataset (n=838) as genetic instruments. Single-nucleotide polymorphism (SNP) associations with lipid traits were obtained from the UK Biobank, including low-density lipoprotein cholesterol (LDL-C; n=440,546) and triglycerides (TGs; n=441,016), and colocalization analysis was used to prioritize robust target genes. Outcome data were derived from FinnGen in predominantly European populations, including bladder cancer (2,053 cases and 287,137 controls), renal cell carcinoma (2,223 cases and 287,137 controls), prostate cancer (13,216 cases and 119,948 controls), carcinoma of the renal pelvis (125 cases and 287,137 controls), and testicular cancer (407 cases and 119,948 controls) . Causal effects were primarily estimated using the inverse-variance weighted (IVW) method, with additional sensitivity analyses to assess pleiotropy, heterogeneity, and robustness. For external validation of the causal associations, we repeated the drug-target MR analyses using Global Lipids Genetics Consortium (GLGC) lipid summary statistics instead of the UK Biobank data, while retaining the  \nsame tumor outcome datasets. Coronary artery disease (CAD) was included as a positive control outcome.  \nResults: Genetically proxied inhibition of ANGPTL3 was associated with a higher risk of prostate cancer [odds ratio (OR) =1.365; 95% confidence interval (CI): 1.091–1.709], whereas genetically proxied inhibition of HMGCR (OR =0 . 718; 95% CI: 0.559–0. 924) and NPC1L1 (OR =0 .274; 95% CI: 0.137–0. 550) was associated with a lower risk. For bladder cancer, inhibition of LPL (OR =1 .455; 95% CI: 1.136–1. 863) and PCSK9 (OR =1 . 757; 95% CI: 1.151–2.684) was associated with increased risk. ANGPTL3 inhibition was also associated with an increased risk of renal cell carcinoma (OR =1 .975; 95% CI: 1.217–3.205) . In testicular cancer, inhibition of NPC1L1 (OR =0 .017; 95% CI: 0.001–0.295) and APOB (","cbCainidg5K6Da8X","https://ap.wps.com/l/cbCainidg5K6Da8X","pdf",2977586,13,"English","# Background\n# Methods\n# Results\n# Conclusions\n# Introduction\n# Highlight box","[{\"question\":\"What was the study’s main objective?\",\"answer\":\"To evaluate whether lipid-lowering drug targets have causal, heterogeneous associations with urologic and male reproductive cancer risks using a drug-target Mendelian randomization design.\"},{\"question\":\"Which datasets were used to derive genetic instruments and outcomes?\",\"answer\":\"Cis-expression quantitative trait loci from GTEx v8 were used as instruments, lipid associations were taken from UK Biobank, and cancer outcomes were obtained from FinnGen, with validation using GLGC lipid summary statistics.\"},{\"question\":\"What key causal associations were found across cancer types?\",\"answer\":\"Genetically proxied inhibition of HMGCR and NPC1L1 related to lower prostate cancer risk, while PCSK9 showed higher risk for bladder cancer; ANGPTL3 inhibition and reduced LPL activity were linked to increased risks of selected urologic cancers.\"},{\"question\":\"How did the authors test the robustness of causal estimates?\",\"answer\":\"They used inverse-variance weighted estimation and additional sensitivity analyses addressing pleiotropy, heterogeneity, and robustness, including leave-one-out analyses, and confirmed key findings in external validation.\"}]","The role of lipid-lowering drugs in urologic and male reproductive cancers - a Mendelian randomization study | PDF",1790152216,33]