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MR-Egger and weighted median sensitivity approaches addressed horizontal pleiotropy, and colocalization supported further validation. Results indicate specific immune phenotypes causally relate to breast, ovarian, and cervical cancer risk.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & Report",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/causal-relationship-between-immune-cells-and-gynecological-cancers-through-bidirectional-and-multivariable-mendelian-randomization-analyses/333188/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/causal-relationship-between-immune-cells-and-gynecological-cancers-through-bidirectional-and-multivariable-mendelian-randomization-analyses/333188.png","ImageObject",300,407,{"name":42,"@type":43},"Anda","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-11-03","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",14,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What method was used to test causal relationships between immune cells and gynecological cancers?","Question",{"text":63,"@type":64},"The study used bidirectional two-sample Mendelian randomization with Wald ratio for a single SNP and inverse-variance weighted analysis for multiple SNPs, based on GWAS data.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How did the study address potential pleiotropy and bias?",{"text":68,"@type":64},"MR-Egger and weighted median methods were used to detect and correct horizontal pleiotropy, and sensitivity analyses indicated almost no evidence of bias.",{"name":70,"@type":61,"acceptedAnswer":71},"Which immune cell phenotypes showed causal associations with cancer risks?",{"text":72,"@type":64},"In IVW analyses, circulating CD11c+ HLA-DR++ conventional dendritic cells increased breast cancer risk; other dendritic cell phenotypes were protective. The study also found causal links involving Treg and CD8+ T cell traits with ovarian and cervical cancer, respectively.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},333188,1790636481,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,111,115,120,123,127],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":108,"show_sort_weight":109,"slug":110},7,"Healthcare",40,"healthcare",{"id":112,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":113,"slug":114},8,30,"research-report",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":124,"doc_module":4,"doc_module_name":25,"category_name":125,"show_sort_weight":124,"slug":126},10,"Lifestyle","lifestyle",{"id":128,"doc_module":4,"doc_module_name":25,"category_name":129,"show_sort_weight":97,"slug":130},19,"General","general",{"code":4,"msg":82,"data":132},{"doc_id":79,"user_id":133,"nickname":42,"user_avatar":134,"doc_module":4,"category_id":112,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":124,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":145,"preview_page_count":4},962075006959,"https://ap-avatar.wpscdn.com/avatar/e0002397efbe92a78e?_k=1776741047341049297","Ivyspring  \nInternational Publisher  \nJournal of Cancer  \n2024; 15(7): 1880-1889. doi: 10.7150/jca.92627  \nResearch Paper  \nCausal Relationship between Immune Cells and Gynecological Cancers through Bidirectional and Multivariable Mendelian Randomization Analyses  \nYangyang Zhang1*, Yangyuxiao Lu2*, Xuanyu Wang3*, Keren He2, Mengqi Fang2, Jiabao Xu4, Ye Xu4, Fangfang Tao4􀀍, Ping Lü5􀀍  \n1. Institute of Obstetrics and Gynecology, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai, China; Shanghai Medical College, Fudan University, Shanghai, China.  \n2. The First Clinical Medical College, Zhejiang Chinese Medicine University, Hangzhou, Zhejiang, China.  \n3. College of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.  \n4. Department of Immunology and Microbiology, Basic Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.  \n5. Department of TCM, Taizhou First People’s Hospital, Taizhou, Zhejiang 318020, China.  \n*These authors contributed equally to this work and should be considered co-first authors.  \n􀀍 Corresponding authors: Fangfang Tao, email address: [taoff@zcmu.edu.cn](taoff@zcmu.edu.cn); Ping Lü, email address: [loveclub98@163.com](loveclub98@163.com).  \n© The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License ([https://creativecommons.org/licenses/by/4.0/](https://creativecommons.org/licenses/by/4.0/)). See [http://ivyspring.com/terms](http://ivyspring.com/terms) for full terms and conditions.  \nReceived: 2023.11.26; Accepted: 2024.01.27; Published: 2024.02.04  \nAbstract  \nBackground: Evidence suggests potential associations between gynecological malignancies and various immune cell chemicals and systems. However, establishing a causal relationship remains uncertain. Methods: This work employed Wald ratio for one single-nucleotide polymorphism (SNP) or the inverse-variance weighted method (IVW) for multiple SNPs to conduct bidirectional two-sample Mendelian randomization (MR) analysis by utilizing genome-wide association study (GWAS) data. We employed supplementary methods, including MR-Egger and weighted median methods, to detect and correct for the influence of horizontal pleiotropy. In addition, we also use colocalization analysis for further validation.  \nResults: In IVW analysis, increases in relative count of circulating CD11c+ HLA-DR++ conventional dendritic cells (cDC) were associated with an elevated risk of breast cancer (OR [95% CI], 1.1295 [1.0632-1.2000], P = 8.044 × 10-5), while elevated levels of HLA-DR on plasmacytoid dendritic cells (DC) and HLA-DR on DC were protective against breast cancer. In addition, actual count of CD39+ resting Treg AC was also shown to be causally associated with the development of ovarian cancer, whereas a high relative count of CD28+ CD45RA- CD8+ T cells reduced the risk of cervical cancer. Sensitivity analysis revealed almost no evidence of bias in the current study. Multivariable MR (MVMR) analyses further confirmed a direct impact of the CD11c+ HLA-DR++ cDC immune phenotype on breast cancer. Colocalization analysis showed the lead SNP, rs780094, suggesting HLA-DR GWAS shared a common genetic mechanism with breast cancer.  \nConclusions: The MR study identified significant causal relationships between multiple immunophenotypes and breast cancer, aiming to provide clinicians with some reference for cancer prediction and explore further potential associations between immune phenotypes and gynecologic tumors.  \nKeywords: immune, gynecological malignancies, breast cancer, Mendelian randomization  \n1. Introduction  \nGynecologic neoplasms represent a substantial public health concern, affecting a significant portion of the population. The American Cancer Society  \nrecently released statistics showing that breast cancer (BRCA) is the most frequent cancer in women worldwide and accounts for one-third of all  \nmalignancies diagnosed i","cbCaiqvrPEKxb9TD","https://ap.wps.com/l/cbCaiqvrPEKxb9TD","pdf",3481560,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusions\n# 1. Introduction","[{\"question\":\"What method was used to test causal relationships between immune cells and gynecological cancers?\",\"answer\":\"The study used bidirectional two-sample Mendelian randomization with Wald ratio for a single SNP and inverse-variance weighted analysis for multiple SNPs, based on GWAS data.\"},{\"question\":\"How did the study address potential pleiotropy and bias?\",\"answer\":\"MR-Egger and weighted median methods were used to detect and correct horizontal pleiotropy, and sensitivity analyses indicated almost no evidence of bias.\"},{\"question\":\"Which immune cell phenotypes showed causal associations with cancer risks?\",\"answer\":\"In IVW analyses, circulating CD11c+ HLA-DR++ conventional dendritic cells increased breast cancer risk; other dendritic cell phenotypes were protective. The study also found causal links involving Treg and CD8+ T cell traits with ovarian and cervical cancer, respectively.\"}]","Causal Relationship between Immune Cells and Gynecological Cancers through Bidirectional and Multivariable Mendelian Randomization Analyses | PDF",1790001340,25]