[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-330524-105":59,"doc-detail-330524-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","identifying-therapeutic-targets-for-cancer-among-2074-circulating-proteins-and-risk-of-nine-cancers","Identifying therapeutic targets for cancer among 2074 circulating proteins and risk of nine cancers","","Study examines 2,074 circulating proteins to clarify therapeutic opportunities for cancer prevention across risk of nine common cancers: bladder, breast, endometrium, head and neck, lung, ovary, pancreas, kidney, and malignant non-melanoma. Using cis protein Mendelian randomisation and colocalization, the work finds 40 cancer-associated proteins, including PLAUR for breast cancer and CTRB1 for pancreatic cancer. Additional analyses assess adverse side-effects of modifying risk proteins and connect risk proteins to existing drugs.",{"@graph":69,"@context":122},[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":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/identifying-therapeutic-targets-for-cancer-among-2074-circulating-proteins-and-risk-of-nine-cancers/330524/",{"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/identifying-therapeutic-targets-for-cancer-among-2074-circulating-proteins-and-risk-of-nine-cancers/330524.png","ImageObject",300,407,{"name":92,"@type":93},"Emma Wilson","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":29},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What study design is used to link circulating proteins to cancer risk?","Question",{"text":112,"@type":113},"The study uses cis protein Mendelian randomisation and colocalization to investigate associations between circulating proteins and the risk of nine cancers.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How many proteins and cancers are analyzed?",{"text":117,"@type":113},"The analysis covers 2,074 circulating proteins and the risk of nine common cancers.",{"name":119,"@type":110,"acceptedAnswer":120},"What additional work is done beyond identifying protein–cancer links?",{"text":121,"@type":113},"The study evaluates potential adverse effects of protein-altering interventions and maps cancer risk proteins to existing drug targets.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},330524,1790909780,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":29,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},3848291630094,"https://eur-avatar.wpscdn.com/davatar_085a072bc5b1113ac321206ff7593b45","Article [https://doi.org/10.1038/s41467-024-46834-3](https://doi.org/10.1038/s41467-024-46834-3)  \nIdentifying therapeutic targets for cancer among 2074 circulating proteins and risk of nine cancers  \nReceived: 12 May 2023  \n\n| Accepted: 5 March 2024 |\n| --- |\n| |\n| Check for updates |\n\nKarl Smith-Byrne 1 , Åsa Hedman2,3, Marios Dimitriou 2,3, Trishna Desai1, Alexandr V. Sokolov4, Helgi B. Schioth4, Mine Koprulu 5, Maik Pietzner 5,6,7, Claudia Langenberg 5,6,7, Joshua Atkins 1, Ricardo Cortez Penha8,  \nJames McKay8, Paul Brennan8, Sirui Zhou 9, Brent J. Richards 10,  \nJames Yarmolinsky11, Richard M. Martin 11,12,13, Joana Borlido 14,  \nXinmeng J. Mu15, Adam Butterworth 16, Xia Shen 17, Jim Wilson17, Themistocles L. Assimes 18, Rayjean J. Hung 19, Christopher Amos 20, Mark Purdue21, Nathaniel Rothman22, Stephen Chanock 21, Ruth C. Travis1,23, Mattias Johansson8,23 & Anders Mälarstig2,3,23  \nCirculating proteins can reveal key pathways to cancer and identify therapeutic targets for cancer prevention. We investigate 2,074 circulating proteins and risk of nine common cancers (bladder, breast, endometrium, head and neck, lung, ovary, pancreas, kidney, and malignant non-melanoma) using cis protein Mendelian randomisation and colocalization. We conduct additional analyses to identify adverse side-effects of altering risk proteins and map cancer risk proteins to drug targets. Here we find 40 proteins associated with common cancers, such as PLAUR and risk of breast cancer [odds ratio per standard deviation increment: 2.27, 1.88-2.74], and with high-mortality cancers, such as CTRB1 and pancreatic cancer [0.79, 0.73-0.85]. We also identify potential adverse effects of protein-altering interventions to reduce cancer risk, such as hypertension. Additionally, we report 18 proteins associated with cancer risk that map to existing drugs and 15 that are not currently under clinical investigation. In sum, we identify protein-cancer links that improve our understanding of cancer aetiology. We also demonstrate that the wider consequence of any protein-altering intervention on well-being and morbidity is required to interpret any utility of proteins as potential future targets for therapeutic prevention.  \nProteins govern cellular action in all human biological processes and are crucial for our defences against both the onset and progression of cancer. Identifying circulating proteins important to the aetiology of cancer may improve our understanding of pathways leading to cancer and highlight potential targets for therapeutic prevention. Circulating proteins are valuable candidate targets for drug development since  \ndrug-target engagement can be evaluated in the bloodstream during randomised control trials (RCTs), accelerating target development. Additionally, identifying circulating cancer risk proteins allows for the subsequent selection of future RCT participants with risk-inducing protein concentrations, which may improve RCT effectiveness. Developing therapeutic prevention strategies, either alone or as a  \nA full list of affiliations appears at the end of the paper. e-mail: [karl.smith-byrne@ndph.ox.ac.uk](karl.smith-byrne@ndph.ox.ac.uk)  \ncomplement to existing prevention programs, such as smoking cessation, are urgently needed given cancer burden is projected to double by the year 20401.  \nTherapeutic prevention is an effective and commonly used strategy for the primary prevention of some common chronic diseases. Prevention strategies have thus far been most successful for cardiovascular disease using statins that target the HMG-CoA reductase protein as a first-line treatment to lower low-density lipoprotein (LDL) cholesterol2,3. In contrast, efforts to identify targets for the therapeutic prevention of cancer have been less fruitful, hampered by a more complex aetiology and difficulty identifying potential targetable aetiological biomarkers4. Exceptions include therapeutically targeting theoestrogen receptor(ER) to prevent breast cancer5 an","cbCain0LSkymawG9","https://ap.wps.com/l/cbCain0LSkymawG9","pdf",1944664,11,"English","# Introduction\n## Therapeutic prevention and target discovery\n## Mendelian randomisation using circulating proteins","[{\"question\":\"What study design is used to link circulating proteins to cancer risk?\",\"answer\":\"The study uses cis protein Mendelian randomisation and colocalization to investigate associations between circulating proteins and the risk of nine cancers.\"},{\"question\":\"How many proteins and cancers are analyzed?\",\"answer\":\"The analysis covers 2,074 circulating proteins and the risk of nine common cancers.\"},{\"question\":\"What additional work is done beyond identifying protein–cancer links?\",\"answer\":\"The study evaluates potential adverse effects of protein-altering interventions and maps cancer risk proteins to existing drug targets.\"}]","Identifying therapeutic targets for cancer among 2074 circulating proteins and risk of nine cancers | PDF",1789989273,28]