{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T07:11:16Z","timestamp":1787987476195,"version":"build-2784847793"},"reference-count":53,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Epidemiologic studies have reported inconsistent altered cancer risk in individuals with multiple sclerosis (MS). Factors such as immune dysregulation, comorbidities, and disease\u2010modifying 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used large\u2010scale genetic studies for MS (47,429 cases, 68,374 controls) and 12 cancers (sample size 85,716 to 417,127). Two\u2010sample 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      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\u2010cancer pairs across nine loci, implicating shared genetic mechanisms in six cancers. Ten out of the 12 colocalization pairs demonstrated antagonistic pleiotropy (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.019). For example, variants in the\n                      <jats:italic>BACH2<\/jats:italic>\n                      locus were associated with opposing risks for MS and non\u2010melanoma skin cancers (posterior probability &gt;\u20090.99). Fine mapping identified the rs72928038 variant as likely causal, its minor allele reducing\n                      <jats:italic>BACH2<\/jats:italic>\n                      expression and increasing MS risk but decreasing skin cancer risk.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.70298","type":"journal-article","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T08:40:09Z","timestamp":1768552809000},"page":"1249-1257","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Shared Genetic Effects and Antagonistic Pleiotropy Between Multiple Sclerosis and Common Cancers"],"prefix":"10.1002","volume":"13","author":[{"given":"Asli","family":"Buyukkurt","sequence":"first","affiliation":[{"name":"The Neuro (Montreal Neurological Institute\u2010Hospital)  Montr\u00e9al Quebec Canada"},{"name":"Department of Neurology and Neurosurgery McGill University  Montr\u00e9al Quebec 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