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The study addresses the uncertainty left by observational evidence, where hormonal imbalance is implicated but directionality cannot be established. Two-sample MR uses public GWAS resources and applies IVW, MR-Egger, weighted median, and weighted mode, supported by sensitivity tests to assess robustness and potential violations such as pleiotropy. Results indicate increased risk for several ovarian cancer subtypes, breast cancer, and brain tumor, alongside a decreased risk for gastric cancer, with consistent causal effects under sensitivity analyses.",{"@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/causal-relationship-between-genetically-predicted-uterine-leiomyoma-and-cancer-risk-a-two-sample-mendelian-randomization/332459/",{"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/causal-relationship-between-genetically-predicted-uterine-leiomyoma-and-cancer-risk-a-two-sample-mendelian-randomization/332459.png","ImageObject",300,407,{"name":92,"@type":93},"Theodore","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-27","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What was the study purpose regarding uterine leiomyoma and cancer risk?","Question",{"text":112,"@type":113},"To determine whether the causal associations between uterine leiomyoma (UL) and cancers are present, since observational studies show correlation but not causality.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How was causality assessed in this research?",{"text":117,"@type":113},"The study used two-sample Mendelian randomization (MR) based on public genetic databases, applying IVW, MR-Egger, weighted median, and weighted mode, with sensitivity tests for robustness.",{"name":119,"@type":110,"acceptedAnswer":120},"Which cancer risks increased or decreased with genetically predicted UL?",{"text":121,"@type":113},"Genetically predicted UL increased risk for low malignant potential ovarian cancer, serous ovarian cancer, invasive mucinous ovarian cancer, clear cell ovarian cancer, breast cancer, and brain tumor. It reduced the risk of gastric cancer.","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},332459,1790730367,{"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":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":39,"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":46,"preview_page_count":4},7971461740886,"https://ap-avatar.wpscdn.com/davatar_3d24733baf745e90a7e4bdd5f77d97b2","TYPE Systematic Review PUBLISHED 29 August 2024  \nDOI 10.3389/fendo.2024.1429165  \nOPEN ACCESS  \nEDITED BY  \nMaria Magdalena Montt-Guevara, University of Pisa, Italy  \nREVIEWED BY  \nMarcos Edgar Herkenhoff, University of São Paulo, Brazil Georgia Damoraki,  \nNational and Kapodistrian University of Athens, Greece  \n*CORRESPONDENCE Lixiu Peng  \n [plx96@163.com](plx96@163.com)[ ](plx96@163.com)Chaoyan Yue  \n [20111250007@fudan.edu.cn](20111250007@fudan.edu.cn)[ ](20111250007@fudan.edu.cn)†These authors share first authorship  \nRECEIVED 07 May 2024  \nACCEPTED 26 July 2024  \nPUBLISHED 29 August 2024  \nCITATION  \nZhao C, Shang A, Wu H, Li Q, Peng Land Yue C (2024) Causal relationship between genetically predicted uterine leiomyoma and cancer risk: a two-sample Mendelian randomization.  \nFront. Endocrinol. 15:1429165 .  \ndoi: 10.3389/fendo.2024.1429165  \nCOPYRIGHT  \n© 2024 Zhao, Shang, Wu, Li, Peng and Yue. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nCausal relationship between genetically predicted uterine leiomyoma and cancer risk: a two-sample Mendelian randomization  \nChenyang Zhao 1†, Anquan Shang 2†, Han Wu 3†, Qiong Li 1, Lixiu Peng 1* and Chaoyan Yue 4*  \n1 Department of Obstetrics and Gynecology, The First People ’s Hospital of Chenzhou,  \nChenzhou, China, 2 Department of Laboratory Medicine, The Second People’s Hospital of Lianyungang & The Oncology Hospital of Lianyungang, Xuzhou Medical University Lianyungang Second Hospital & Jiangsu University Lianyungang Second Hospital, Lianyungang, China, 3Clinical Laboratory, Shanghai Children ’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China, 4Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China  \nPurpose: Studies have demonstrated that hormonal imbalance, such as elevated level of estrogen or reduced level of progesterone, was the main inducing factor of uterine leiomyoma (UL) development and some cancers. UL has been reported to be associated with several cancers in observational studies. However, the causal associations between UL and cancers remain unclear.  \nMethods: A two-sample Mendelian randomization (MR) analysis was conducted to investigate the causal associations between UL and 16 site-specific cancers using the public databases. Four methods, namely, the inverse variance weighting (IVW), MR-Egger, weighted median, and weighted mode, were applied in our MR analysis. Sensitivity tests were also performed to evaluate the robustness of these causal associations.  \nResults: The IVW analysis indicated that genetically predicted UL increased the risk of low malignant potential ovarian cancer [odds ratio (OR) = 1.22, 95% confidence interval (CI): 1 .06–1. 40, p = 0 . 004], serous ovarian cancer (OR = 1 . 29, 95% CI: 1 .10–1. 52, p = 0 . 002), invasive mucinous ovarian cancer (OR = 1 . 24, 95% CI: 1 .08–1.44, p = 0 . 003), clear cell ovarian cancer (OR = 1 . 25, 95% CI: 1 .03–1. 51, p = 0 . 023), breast cancer (OR = 1 . 07, 95% CI: 1 .02–1. 11, p = 0 . 002), and brain tumor (OR = 1 . 23, 95% CI: 1 .06–1. 42, p = 0 . 007) . Conversely, genetically predicted UL reduced the risk of gastric cancer  \nAbbreviations: UL, Uterine leiomyoma; MR, Mendelian randomization; GWAS, Genome-wide association study; IVs, Instrumental variables; SNP, Single-nucleotide polymorphism; ICD, International Classification of Diseases; IEU, Integrative Epidemiology Unit; IVW, Inverse variance weighting; FinnGen, FinnGen Consortium; IEU, IEU open GWAS project; OR, Odds ratio; CI, Confidence interval; PRESSO, Pleiotropy Residual Sum and Outlier; ConMix, Conta","cbCaio0TBRDLiV9o","https://ap.wps.com/l/cbCaio0TBRDLiV9o","pdf",3271619,"English","# Purpose\n# Methods\n# Results\n## Key cancer site findings\n# Conclusions\n# Abbreviations","[{\"question\":\"What was the study purpose regarding uterine leiomyoma and cancer risk?\",\"answer\":\"To determine whether the causal associations between uterine leiomyoma (UL) and cancers are present, since observational studies show correlation but not causality.\"},{\"question\":\"How was causality assessed in this research?\",\"answer\":\"The study used two-sample Mendelian randomization (MR) based on public genetic databases, applying IVW, MR-Egger, weighted median, and weighted mode, with sensitivity tests for robustness.\"},{\"question\":\"Which cancer risks increased or decreased with genetically predicted UL?\",\"answer\":\"Genetically predicted UL increased risk for low malignant potential ovarian cancer, serous ovarian cancer, invasive mucinous ovarian cancer, clear cell ovarian cancer, breast cancer, and brain tumor. It reduced the risk of gastric cancer.\"}]","Causal relationship between genetically predicted uterine leiomyoma and cancer risk - a two-sample Mendelian randomization | PDF",1789998293]