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Colocalization identified 12 MS-cancer pairs across nine loci, and most pairs showed antagonistic pleiotropy where variants increase MS risk but decrease cancer susceptibility.","https://schema.org",{"og:url":32,"og:type":74,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":76,"canonical":32},"index,follow",{"doc_id":78,"site_id":7},345559,1790176941,{"code":4,"msg":81,"data":82},"success",[83,87,91,95,100,105,109,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":84,"show_sort_weight":85,"slug":86},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":88,"show_sort_weight":89,"slug":90},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":92,"show_sort_weight":93,"slug":94},"Exam",70,"exam",{"id":96,"doc_module":4,"doc_module_name":25,"category_name":97,"show_sort_weight":98,"slug":99},5,"Comic",60,"comic",{"id":101,"doc_module":4,"doc_module_name":25,"category_name":102,"show_sort_weight":103,"slug":104},6,"Technology",50,"technology",{"id":106,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":107,"slug":108},7,40,"healthcare",{"id":110,"doc_module":4,"doc_module_name":25,"category_name":111,"show_sort_weight":112,"slug":113},8,"Research & Report",30,"research-report",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},9,"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":96,"slug":129},19,"General","general",{"code":4,"msg":81,"data":131},{"doc_id":78,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":106,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":30,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":115,"language":139,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":12,"update_tm":143,"read_time":144},13056703019404,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","Annals of Clinical and Translational Neurology   \n RESEARCH ARTICLE  OPEN ACCESS   \nShared Genetic Effects and Antagonistic Pleiotropy Between Multiple Sclerosis and Common Cancers  \nAsli Buyukkurt1,2 | Marius Ygonia3 | Ali Manouchehrinia4  | Philippe Lefrançois5,6,7,8 | Ingrid Kockum4  | Adil Harroud1,2,3,4,9   \n1The Neuro (Montreal Neurological Institute-Hospital), Montréal, Quebec, Canada | 2Department of Neurology and Neurosurgery, McGill University, Montréal, Quebec, Canada | 3Department of Human Genetics, McGill University, Montréal, Quebec, Canada | 4Center for Molecular Medicine, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden | 5Cancer Axis, Lady Davis Institute for Medical Research, Montreal, Quebec, Canada | 6Division of Dermatology, Department of Medicine, Jewish General Hospital, McGill University, Montreal, Quebec,  \nCanada | 7Department of Pharmacology & Therapeutics, McGill University, Montreal, Quebec, Canada | 8Division of Surgical and Interventional Sciences, Department of Medicine, McGill University, Montreal, Quebec, Canada | 9Victor Phillip Dahdaleh Institute of Genomic Medicine, McGill University, Montreal, Quebec, Canada  \nCorrespondence: Adil Harroud ([adil.harroud@mcgill.ca](adil.harroud@mcgill.ca))  \nReceived: 30 May 2025 | Revised: 25 November 2025 | Accepted: 12 December 2025  \nKeywords: cancer | mendelian randomization | multiple sclerosis  \nABSTRACT  \nObjective: Epidemiologic studies have reported inconsistent altered cancer risk in individuals with multiple sclerosis (MS) . Factors such as immune dysregulation, comorbidities, and disease-modifying therapies may contribute to this variability. This study aimed to assess the potential causal effects and shared genetic risk between MS and 12 common cancers.  \nMethods: We used large-scale genetic studies for MS (47,429 cases, 68,374 controls) and 12 cancers (sample size 85,716 to 417,127) . Two-sample Mendelian randomization (MR) was performed to estimate the causal effect of genetic liability to MS on cancer risk. Colocalization analysis was employed to identify shared genetic loci between MS and cancers. Tissue enrichment analyses for prioritized genes and directionality tests were performed.  \nResults: MR analyses found no evidence for a causal effect of MS liability on cancer risk after correcting for multiple testing. Colocalization analysis revealed 12 MS-cancer pairs across nine loci, implicating shared genetic mechanisms in six cancers. Ten out of the 12 colocalization pairs demonstrated antagonistic pleiotropy (p = 0.019) . For example, variants in the BACH2 locus were associated with opposing risks for MS and non-melanoma skin cancers (posterior probability >0.99) . Fine mapping identified the rs72928038 variant as likely causal, its minor allele reducing BACH2 expression and increasing MS risk but decreasing skin cancer risk.  \nInterpretation: While no causal relationship between MS liability and cancer risk was identified, shared genetic effects highlight potential biological mechanisms linking immune regulation in MS and cancer risk. The observed antagonistic pleiotropy, where genetic variants increase MS risk but decrease cancer susceptibility, mirrors patterns seen in autoimmunity and infection.  \n\n| Asli Buyukkurt and Marius Ygonia contributed equally to this work. |\n| --- |\n| This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.\u003Cbr>© 2026 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. |\n\nAnnals of Clinical and Translational Neurology, 2026; 13:1249–1257 1249  \n[https://doi.org/10.1002/acn3.70298](https://doi.org/10.1002/acn3.70298)  \n1 | Introduction  \nAn altered risk of cancer has ","cbCaidOYj40uoMJq","https://ap.wps.com/l/cbCaidOYj40uoMJq","pdf",912367,"English","# Introduction\n# Objective and Methods\n# Results\n## Mendelian randomization findings\n## Colocalization and pleiotropy findings\n# Interpretation","[{\"question\":\"What problem does the study address about cancer risk in multiple sclerosis?\",\"answer\":\"Prior epidemiologic studies show conflicting cancer risk patterns in people with MS. The study investigates whether the inconsistency reflects causal effects, shared genetic susceptibility, or both.\"},{\"question\":\"How were causal effects and shared genetic risk assessed?\",\"answer\":\"The study used two-sample Mendelian randomization to estimate the causal effect of genetic liability to MS on cancer risk, and colocalization to identify shared genetic loci between MS and cancers.\"},{\"question\":\"What did the results show about the relationship between MS liability and cancer risk?\",\"answer\":\"After multiple-testing correction, Mendelian randomization found no evidence that MS liability causally increases cancer risk. Colocalization identified 12 MS-cancer pairs across nine loci, and most pairs showed antagonistic pleiotropy where variants increase MS risk but decrease cancer susceptibility.\"}]","Shared Genetic Effects and Antagonistic Pleiotropy Between Multiple Sclerosis and Common Cancers | PDF",1790058089,23]