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This study evaluates the scope and intensity of colon field cancerization using DNA methylation. Using the Swiss Epigenetic Colorectal Cancer Study (SWEPIC) with 1111 participants, methylation variability discriminates healthy tissue from tissue adjacent to adenomatous polyps. Dysregulation occurs at hundreds of loci, correlates with polyp multiplicity and age, and shows genomic enrichment with altered gene expression. External validation supports early right-colon onset, suggesting aDVMCs as a stratification and surveillance support tool.",{"@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/dna-methylation-variability-in-normal-mucosa-a-field-cancerization-marker-in-patients-with-adenomatous-polyps/328001/",{"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/dna-methylation-variability-in-normal-mucosa-a-field-cancerization-marker-in-patients-with-adenomatous-polyps/328001.png","ImageObject",300,407,{"name":92,"@type":93},"Hazel","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-04","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What does field cancerization mean in this study?","Question",{"text":112,"@type":113},"It refers to the transition from normal cells to a cancer-prone population that has undergone only some required changes for malignancy. The work focuses on assessing its scope in the colon.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How was field cancerization detected and evaluated?",{"text":117,"@type":113},"The study used DNA methylation data from the SWEPIC cohort, assessing methylation variability and testing discriminative performance in distinguishing healthy from adenoma-adjacent tissues. Validation was performed in external cohorts and related analyses.",{"name":119,"@type":110,"acceptedAnswer":120},"What key associations were found for adenoma-related differentially variable and methylated CpGs (aDVMCs)?",{"text":121,"@type":113},"aDVMC dysregulation correlated with polyp multiplicity and more than half of aDVMCs were significantly associated with age. aDVMCs were enriched in active genomic regions and linked to altered RNA expression in adenoma-adjacent tissue.","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},328001,1790195939,{"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":39,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":52,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144,"preview_page_count":4},137441390410,"https://ap-avatar.wpscdn.com/avatar/2000252f4ab5702993?_k=1776741390130283984","JNCI: Journal of the National Cancer Institute, 2024, 116(6), 974–982  \n[https://doi.org/10.1093/jnci/djae016](https://doi.org/10.1093/jnci/djae016)  \nAdvance Access Publication Date: January 25, 2024  \nArticle  \nDNA-methylation variability in normal mucosa: a field cancerization marker in patients with adenomatous polyps  \nJosephine Yates, MSc1,2,3, Helen Schaufelberger, MD, PhD4, Roland Steinacher, PhD5, Primo Sch€ar, PhD5, Kaspar Truninger , MD, PhD5,6,􀀃 ,‡, Valentina Boeva , PhD1,2,3,7,‡  \n1Department of Computer Science, Institute for Machine Learning, ETH Z€urich, Zurich, Switzerland 2ETH AI Center, ETH Z€urich, Zurich, Switzerland  \n3Swiss Institute for Bioinformatics (SIB), Lausanne, Switzerland 4Clinica Luganese Moncucco, Lugano, Switzerland  \n5Department of Biomedicine, University of Basel, Basel, Switzerland  \n6Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland  \n7Cochin Institute, Inserm U1016, National Centre for Scientific Research (CNRS) UMR 8104, Paris Descartes University UMR-S1016, Paris, France  \n􀀃 Correspondence to: Kaspar Truninger, MD, PhD, Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland, R€amistrasse  \n100, 8091 Z€urich, Switzerland ([e-mail: k.truninger@hin.ch](e-mail: k.truninger@hin.ch)) .  \n‡These authors contributed equally to this work.  \nAbstract  \nBackground: The phenomenon of field cancerization reflects the transition of normal cells into those predisposed to cancer. Assessing the scope and intensity of this process in the colon may support risk prediction and colorectal cancer prevention.  \nMethods: The Swiss Epigenetic Colorectal Cancer Study (SWEPIC) study, encompassing 1111 participants for DNA methylation analysis and a subset of 84 for RNA sequencing, was employed to detect field cancerization in individuals with adenomatous polyps (AP) . Methylation variations were evaluated for their discriminative capability, including in external cohorts, genomic localization, clinical correlations, and associated RNA expression patterns.  \nResults: Normal cecal tissue of individuals harboring an AP in the proximal colon manifested dysregulated DNA methylation compared to tissue from healthy individuals at 558 unique loci. Leveraging these adenoma-related differentially variable and methylated CpGs (aDVMCs), our classifier discerned between healthy and AP-adjacent tissues across SWEPIC datasets (cross-validated area under the receiver operating characteristic curve [ROC AUC] ¼ 0.63-0.81), including within age-stratified cohorts. This discriminative capacity was validated in 3 external sets, differentiating healthy from cancer-adjacent tissue (ROC AUC ¼ 0.82-0.88) . Notably, aDVMC dysregulation correlated with polyp multiplicity. More than 50% of aDVMCs were significantly associated with age. These aDVMCs were enriched in active regions of the genome (P \u003C .001), and associated genes exhibited altered expression in AP-adjacent tissues. Conclusions: Our findings underscore the early onset of field cancerization in the right colon during the neoplastic transformation process. A more extensive validation of aDVMC dysregulation as a stratification tool could pave the way for enhanced surveillance approaches, especially given its linkage to adenoma emergence.  \nMolecular aberrations preceding cancer development have been documented in multiple tissues, even before the first clinically detectable lesions are apparent. Field cancerization refers to the replacement of normal cells with a cancer-prone population that has undergone some but not all of the necessary modifications for malignancy (1) . Understanding the occurrence of field cancerization within a specific cancer type is critical to accurately determine the risk of developing a malignancy and, therefore, contribute to cancer prevention.  \nIn colorectal cancer (CRC), field cancerization is of particular interest due to the considerable number of sporadic cases an","cbCaihyvFxDai0Kw","https://ap.wps.com/l/cbCaihyvFxDai0Kw","pdf",1844011,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusions\n# Introduction\n## Field cancerization concept\n## Relevance to colorectal cancer screening\n## Gaps in genome-wide characterization\n# Study rationale and cohort context","[{\"question\":\"What does field cancerization mean in this study?\",\"answer\":\"It refers to the transition from normal cells to a cancer-prone population that has undergone only some required changes for malignancy. The work focuses on assessing its scope in the colon.\"},{\"question\":\"How was field cancerization detected and evaluated?\",\"answer\":\"The study used DNA methylation data from the SWEPIC cohort, assessing methylation variability and testing discriminative performance in distinguishing healthy from adenoma-adjacent tissues. Validation was performed in external cohorts and related analyses.\"},{\"question\":\"What key associations were found for adenoma-related differentially variable and methylated CpGs (aDVMCs)?\",\"answer\":\"aDVMC dysregulation correlated with polyp multiplicity and more than half of aDVMCs were significantly associated with age. aDVMCs were enriched in active genomic regions and linked to altered RNA expression in adenoma-adjacent tissue.\"}]","DNA-methylation variability in normal mucosa - a field cancerization marker in patients with adenomatous polyps | PDF",1789978472,25]