Toxicity related to immunotherapy in urothelial cancer: Tumour genetic risk variants

Toxicity related to immunotherapy in urothelial cancer: Tumour genetic risk variants | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Toxicity related to immunotherapy in urothelial cancer: Tumour genetic risk variants Ana Fernández-Santander, Jose María Rodríguez Piñas, Alicia Romero-Lorca, and 12 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8919966/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 9 You are reading this latest preprint version Abstract The treatment of urothelial cancer (UC) has been revolutionized by the introduction of immune checkpoint inhibitors (ICIs). However, while ICIs have achieved better therapeutic results than traditional chemotherapeutic agents, immune-related adverse events (irAEs) can lead to poor treatment outcomes. This exploratory study was designed to seek tumour single-nucleotide polymorphisms (SNPs) related to irAEs in patients with UC treated with ICIs. Tumour specimens were collected at several hospitals in Madrid (Spain) from 102 patients treated with nivolumab, atezolizumab, avelumab or pembrolizumab. DNA was extracted from formalin-fixed paraffin-embedded tumour biopsies, and 49 SNPs genotyped using a MassARRAY platform. Among the 49 SNPs analyzed, rs1738074 was associated both with overall toxicity (p<0.001), and with the appearance of specific toxicities such as dermatitis and pneumonitis (p=0.005 and p=0.036, respectively). In effect, 100% of patients with pneumonitis were homozygous for the variant allele (p=0.020). Other SNPs were also linked to a higher risk of irAEs: rs2301756 to pneumonitis (p=0.005), rs55733913 and rs2117997 to dermatitis (p=0.026, p=0.021, respectively) and rs4988956 to hepatitis (p=0.027). Contrarily, two SNPs, rs11571302 and rs66502444, showed a possible protective role against asthenia (p=0.012, p=0.030, respectively). This exploratory study highlights the possible useful role of tumour SNPs as biomarkers to predict the risk of UC patients developing irAEs. Further studies are needed to validate the utility of SNPs as biomarkers of ICI-induced toxicity. Biological sciences/Genetics Health sciences/Biomarkers Health sciences/Biomarkers/Predictive markers immunotherapy urothelial cancer toxicity biomarker SNP Full Text Additional Declarations There is NO conflict of interest to disclose. Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: revise 02 Apr, 2026 Review # 2 received at journal 21 Mar, 2026 Reviewer # 2 agreed at journal 13 Mar, 2026 Review # 1 received at journal 11 Mar, 2026 Reviewer # 1 agreed at journal 11 Mar, 2026 Reviewers invited by journal 11 Mar, 2026 Submission checks completed at journal 23 Feb, 2026 Editor assigned by journal 19 Feb, 2026 First submitted to journal 19 Feb, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8919966","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":604576239,"identity":"f9938c9e-7c32-4c80-805c-43ee3c35300e","order_by":0,"name":"Ana 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