[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-342550-105":59,"doc-detail-342550-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","fateful-fat-intra-pancreatic-lipids-cause-pancreatic-cancer","Fateful fat: Intra-pancreatic lipids cause pancreatic cancer","","A Mendelian randomization and prospective cohort analysis finds that intra-pancreatic fat increases the risk of pancreatic cancer, providing human evidence supporting a causal lipid–cancer relationship in the pancreas and confirming the PANDORA hypothesis. The discussion reviews prior observational and meta-analytic evidence linking fatty change in noncancerous pancreatic tissue to PDAC, addresses limits from reverse causation, and explains how genetic variants strengthen causal inference across multiple sensitivity and subgroup approaches.",{"@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":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/fateful-fat-intra-pancreatic-lipids-cause-pancreatic-cancer/342550/",{"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/fateful-fat-intra-pancreatic-lipids-cause-pancreatic-cancer/342550.png","ImageObject",300,407,{"name":92,"@type":93},"Anda","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-23","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":8},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What does the study show about intra-pancreatic fat and pancreatic cancer?","Question",{"text":112,"@type":113},"Intra-pancreatic fat increases pancreatic cancer risk in a Mendelian randomization and prospective cohort framework, supporting a causal relationship rather than mere association.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Why are earlier findings considered limited for proving causality?",{"text":117,"@type":113},"Prior human investigations were mainly conventional observational studies, which cannot determine the direction of causality and may be affected by reverse causation.",{"name":119,"@type":110,"acceptedAnswer":120},"How does Mendelian randomization help address reverse causation and confounding?",{"text":121,"@type":113},"Genetic variants are fixed at conception, making them less likely to be influenced by disease processes and reducing susceptibility to reverse causation and confounding compared with observational designs.","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},342550,1790128246,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":8,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":81,"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":39},962075006959,"https://ap-avatar.wpscdn.com/avatar/e0002397efbe92a78e?_k=1776741047341049297","ll  \nOPEN ACCESS  \nPreview  \nFateful fat: Intra-pancreatic lipids cause pancreatic cancer  \nMaxim S. Petrov1,*  \n1School of Medicine, University of Auckland, Auckland, New Zealand  \n*[Correspondence:](Correspondence: max.petrov@gmail.com)[ max.petrov@gmail.com](Correspondence: max.petrov@gmail.com)  \n[https://doi.org/10.1016/j.xcrm.2024.101428](https://doi.org/10.1016/j.xcrm.2024.101428)  \nIn a Mendelian randomization and prospective cohort study,1 intra-pancreatic fat increases the risk of pancreatic cancer. This provides persuasive human evidence of causal relation between lipids and cancer in the pancreas, which confirms a prediction of the PANDORA hypothesis.  \nPreventing, intercepting, and treating sporadic pancreatic ductal adenocarcinoma (PDAC) is notoriously difficult, at least in part because of incomplete understanding of what causes it. Conspicuous general adiposity is a well-known risk factor for PDAC, but it is non-specific, being associated with cancer in other organs (e.g., esophagus, colon, kidney, and breast) too. Inconspicuous local fat within the pancreas—intra-pancreatic fat deposition (IPFD)—might be a specific determinant of PDAC, and this was the premise of the study by Yamazaki et al.1 in this  \nissue of the Cell Reports Medicine.  \nThe link between IPFD in noncancerous pancreas tissue and PDAC—a cancer characterized by abundant desmoplastic reaction to a relatively small volume of cancer cells—was investigated in several earlier studies. A systematic review and meta-analysis showed that more than half of patients with pancreatic cancer or pre-malignant lesions had fatty change of the pancreas (i.e., disorder characterized by excess IPFD) .2 Moreover, these patients had a nearly 3-fold greater probability of having fatty change of the pancreas in comparison with controls.2 Some studies also found that fatty change of the pancreas was significantly associated with PDAC after taking into account body mass index,3 ,4 suggesting that fatty change of the pancreas is not necessarily a function of general adiposity in patients with PDAC. However, all the primary investigations in humans to date have invariably been conventional observational studies. This is a key barrier to understanding the role of IPFD in PDAC, asthe direction of causality cannot be ascertained from these studies. More specif-  \nically, it is possible that PDAC causes fatty change of the pancreas (e.g., through PDAC-associated pancreatic duct obstruction leading to increased IPFD), in which case pondering about fatty change of the pancreas would have limited clinical implications.  \nThe use of genetic variants as natural experiments—Mendelian randomization—has emerged as an acceptable way to establish causal relation between a modifiable risk factor and a disease because genetic variants are fixed at conception. This method is much less likely to be influenced by reverse causation and confounding (both measured and unmeasured) than conventional observational studies. Yamazaki et al.1 leveraged Mendelian randomization to investigate the link between IPFD and PDAC. The authors employed a total of eight previously identified single-nucleotide polymorphisms of IPFD (below the conventional genome-wide significancep value threshold of 5 3 10􀀁8) and found a statistically significant relation between increased IPFD and PDAC. This consistently held true in a series of sensitivity and subgroup analyses. Notably, when the three genetic variants nominally associated with body mass index were excluded, the relation remained significant (in fact, it became even stronger) . The authors also used an additional study design (a multivariable Cox regression model applied to prospective cohort with a relatively long follow-up period) that yielded a similar result to the two-sample Mendelian randomization analysis and, hence, demonstrated consistency of relation between increased IPFD and PDAC across different study designs.1 This  \nbody of work represents an important con","cbCaiaB1ypXMZnfe","https://ap.wps.com/l/cbCaiaB1ypXMZnfe","pdf",1860612,"English","# Background and rationale\n## Limits of observational evidence\n# Mendelian randomization approach\n## Sensitivity and subgroup consistency\n# Support for the PANDORA hypothesis\n## Mechanistic implications","[{\"question\":\"What does the study show about intra-pancreatic fat and pancreatic cancer?\",\"answer\":\"Intra-pancreatic fat increases pancreatic cancer risk in a Mendelian randomization and prospective cohort framework, supporting a causal relationship rather than mere association.\"},{\"question\":\"Why are earlier findings considered limited for proving causality?\",\"answer\":\"Prior human investigations were mainly conventional observational studies, which cannot determine the direction of causality and may be affected by reverse causation.\"},{\"question\":\"How does Mendelian randomization help address reverse causation and confounding?\",\"answer\":\"Genetic variants are fixed at conception, making them less likely to be influenced by disease processes and reducing susceptibility to reverse causation and confounding compared with observational designs.\"}]","Fateful fat: Intra-pancreatic lipids cause pancreatic cancer | PDF",1790047089]