[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-377704-105":59,"doc-detail-377704-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","rare-germline-variants-in-pancreatic-cancer-and-multiple-primary-cancers-an-autopsy-study","Rare germline variants in pancreatic cancer and multiple primary cancers - an autopsy study","","Rare germline variants that predispose to pancreatic cancer remain insufficiently characterized. This retrospective autopsy case-control study analyzed 61 protein-coding genes in Japanese individuals with negative family history, using targeted sequencing and ACMG/AMP guideline-based pathogenicity classification supported by Polyphen-2, SIFT, and LoFtool. Among 189 subjects, pathogenic/likely pathogenic variants were observed in a small fraction of pancreatic cancer cases, while many cancer patients carried variants of uncertain significance, including associations involving MMR genes and POLQ.",{"@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/rare-germline-variants-in-pancreatic-cancer-and-multiple-primary-cancers-an-autopsy-study/377704/",{"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/rare-germline-variants-in-pancreatic-cancer-and-multiple-primary-cancers-an-autopsy-study/377704.png","ImageObject",300,407,{"name":92,"@type":93},"Lucas Martin","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-27","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":81},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What was the main research aim of the study?","Question",{"text":112,"@type":113},"To characterize rare germline variants in elderly patients with pancreatic cancer and multiple primary cancers using a 61-gene panel approach in autopsy cases with negative family history.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were variants identified and classified in the Methods?",{"text":117,"@type":113},"The study used targeted sequencing of protein-coding regions of 61 genes and classified pathogenicity according to ACMG/AMP guidelines, with Polyphen-2, SIFT, and LoFtool for predicting functional damage.",{"name":119,"@type":110,"acceptedAnswer":120},"What were the key findings regarding pathogenic/likely pathogenic variants and VUS?",{"text":121,"@type":113},"Pathogenic/likely pathogenic variants occurred in a small proportion of pancreatic cancer cases, whereas many cancer patients carried VUS. Associations were reported for specific MMR genes and POLQ with VUS in relevant groups.","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},377704,1790372898,{"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":81,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":41},8796095360427,"https://ap-avatar.wpscdn.com/davatar_994ba38a5ba835b3df7d355c54d3ed8d","286  \nResearch article  \nRare germline variants in pancreatic cancer and multiple primary cancers: an autopsy study  \nHiroo Fujitania, Hidetaka Eguchib, Yuta Kochic,d, Tomio Araie, Masaaki Muramatsua,b and Yasushi Okazakib  \nBackground There is a lack of information on rare germline variants of pancreatic cancer-predisposing genes. Risk genes for multiple primary cancers may overlap with those for pancreatic cancer.  \nMethods A retrospective study of autopsy cases with a negative family history in the Japanese single nucleotide polymorphism for geriatric research database examined rare germline variants in the protein-coding regions of 61 genes. Targeted sequencing of these genes was performed and classified for pathogenicity using the American College of Medical Genetics and Genomics guidelines. Polyphen-2, SIFT and LoFtool algorithms were used to predict damage to protein function.  \nResults Of the 189 subjects used (90 cancer and 99 non-cancer controls), 72 patients had pancreatic cancer (23 had multiple primary cancers) and 18 had no pancreatic cancer in multiple primary cancers. APC, BRCA2, BUB1B, ENG and MSH6 were associated with cancer predisposition, and pathogenic/likely pathogenic (P/LP) variants occurred in 6%[pancreatic cancer (4/72); all-cancer (5/90)] and 54%(49/90) carried only variants of uncertain significance (VUS) among cancer patients. Of these VUS, in pancreatic cancer patients, four DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6 and PMS2), and POLQ in men were significantly associated  \n(odds ratio = 3.83; P= 0.025; P= 0.027, respectively). The most abundant predictor of functionally damaging variants was POLQ.  \nConclusions The frequency of P/LP variants in patients with sporadic pancreatic cancer suggests the need for genetic evaluation of individuals with no family history. VUS of MMR genes (MLH1, MSH2, MSH6 and PMS2) and POLQ may be useful in predicting genetic trends in the potential risk of pancreatic cancer, especially in individuals lacking P/LP. European Journal of Cancer Prevention 32: 286–297 Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.  \nEuropean Journal of Cancer Prevention 2023, 32:286–297  \nKeywords: DNA mismatch repair, double-strand break repair, gene panel sequencing, multiple primary cancer, pancreatic cancer, rare germline variant, variant of uncertain significance  \naDepartment of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, bDiagnostics and Therapeutics of Intractable Diseases, Intractable Disease Research Center, Graduate School of Medicine, Juntendo University, cDepartment of Genomic Function and Diversity, Medical Research Institute, Tokyo Medical and Dental University, dLaboratory for Autoimmune Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa and eDepartment of Pathology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan  \nCorrespondence to Masaaki Muramatsu, MD, PhD, Tokyo Medical and Dental University, Tokyo 113-8510, Japan  \nTel: +81 33 813 6111; [e-mail: muramatsu.epi@mri.tmd.ac.jp](e-mail: muramatsu.epi@mri.tmd.ac.jp)[ ](e-mail: muramatsu.epi@mri.tmd.ac.jp)[Received 24 August 2022 Accepted 17 January 2023](Received 24 August 2022 Accepted 17 January 2023) .  \nIntroduction  \nMost patients with pancreatic cancer are sporadic (Vietriet al., 2022) and the incidence of pancreatic cancer is estimated to increase further. The risk factors for pancreatic cancer include sex, smoking, alcohol consumption, diabetes and family history. Pancreatic cancer is refractory and has a low 5-year survival rate. The etiology of pancreatic cancer is not fully understood. The close agreement between the incidence and mortality rates indicates that only a small fraction of patients are detected in the early stages of efficient intervention. These features highlight  \nSupplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the","cbCaiiaGVF7JbCRM","https://ap.wps.com/l/cbCaiiaGVF7JbCRM","pdf",617376,12,"English","# Background\n# Methods\n# Results\n# Conclusions\n# Introduction","[{\"question\":\"What was the main research aim of the study?\",\"answer\":\"To characterize rare germline variants in elderly patients with pancreatic cancer and multiple primary cancers using a 61-gene panel approach in autopsy cases with negative family history.\"},{\"question\":\"How were variants identified and classified in the Methods?\",\"answer\":\"The study used targeted sequencing of protein-coding regions of 61 genes and classified pathogenicity according to ACMG/AMP guidelines, with Polyphen-2, SIFT, and LoFtool for predicting functional damage.\"},{\"question\":\"What were the key findings regarding pathogenic/likely pathogenic variants and VUS?\",\"answer\":\"Pathogenic/likely pathogenic variants occurred in a small proportion of pancreatic cancer cases, whereas many cancer patients carried VUS. Associations were reported for specific MMR genes and POLQ with VUS in relevant groups.\"}]","Rare germline variants in pancreatic cancer and multiple primary cancers - an autopsy study | PDF",1790226757]