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This study uses bidirectional two-sample Mendelian randomization to test genetic causality between BC and EC, deriving BC instruments from breast cancer GWAS summary statistics and EC data from multiple consortia and the UK Biobank. Inverse-variance weighted primary analysis, supported by MR-Egger, weighted median, pleiotropy and heterogeneity checks, and leave-one-out sensitivity testing, identifies bidirectional genetic causality involving estrogen receptor-positive breast cancer.",{"@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/investigating-the-genetic-causal-relationship-between-breast-cancer-and-endometrial-cancer-a-two-sample-mendelian-randomization-study/332639/",{"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/investigating-the-genetic-causal-relationship-between-breast-cancer-and-endometrial-cancer-a-two-sample-mendelian-randomization-study/332639.png","ImageObject",300,407,{"name":92,"@type":93},"River Wang","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","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 question does the study address about breast cancer and endometrial cancer?","Question",{"text":112,"@type":113},"It examines whether there is a genetic causal relationship between breast cancer (BC) and endometrial cancer (EC), and whether the direction of causality is bidirectional.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were genetic instruments and data sources selected?",{"text":117,"@type":113},"BC genetic instruments were taken from Breast Cancer Association Consortium GWAS summary statistics, while EC data came from the Endometrial Cancer Association Consortium, the Epidemiology of Endometrial Cancer Consortium, and the UK Biobank.",{"name":119,"@type":110,"acceptedAnswer":120},"Which analytical methods were used to test robustness and validity?",{"text":121,"@type":113},"The primary method was inverse-variance weighted, with additional MR-Egger and weighted median analyses. Pleiotropy was assessed using MR-Egger intercept testing, heterogeneity with the Cochrane Q test, and sensitivity with a leave-one-out analysis.","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},332639,1790443975,{"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":34,"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},1099514067438,"https://ap-avatar.wpscdn.com/avatar/100002539ee87300030?x-image-process=image/resize,m_fixed,w_180,h_180&k=1780474512215547542","®  \n Observational Study   \nInvestigating the genetic causal relationship between breast cancer and endometrial cancer A two-sample Mendelian randomization study  \nJian-Cong Wu, MDa ,b , Xiao-Bi Huang, MDa ,b , Yan-Ming Lin, MDa ,b , Qi Zhang, MSb , Xiao-Rao Chen, MDb , Zhong Huang, MSb , Hai-Yin Ye, MSb , Yu-Liu Xie, MDb , Zhi-Xiong Yang, BSb , Wen-Mei Su, MDa ,b ,c ,  \nQi-Biao Wu, MDa ,*  \n\n| Abstract\u003Cbr>Observational studies have consistently shown a correlation between breast cancer (BC) and endometrial cancer (EC) . Despite these findings, the causal relationship between these cancers has not been clearly defined. This research employed a bidirectional two-sample Mendelian randomization to explore the genetic causality between BC and EC. Genetic instruments for BC were derived from the Breast Cancer Association Consortium genome-wide association studies summary statistics, while for EC, data were sourced from the Endometrial Cancer Association Consortium, the Epidemiology of Endometrial Cancer Consortium, and the UK Biobank. The primary analytical method was inverse-variance weighted. Additional analyses, such as MR-Egger and weighted median, were conducted to validate the robustness of our findings from multiple perspectives. The MR-Egger intercept test was conducted to examine potential pleiotropy, whereas Cochrane Q test was implemented to assess heterogeneity. A leave-one-out analysis was conducted to assess the sensitivity of the observed association. Our analysis identified a bidirectional genetic causal relationship between estrogen receptor-positive breast cancer (ER+BC) and EC. Inverse-variance weighted analysis indicatedan odds ratio of 1.0686 (95% confidence interval: 1.0029–1. 1386, P = .0403) from ER+BC to EC and an odds ratio of 1.0692 (95% confidence interval: 1.0183–1. 1225, P = .0071) from EC to ER+BC. No significant horizontal pleiotropy was detected. This study confirms a bidirectional genetic link between ER+BC and EC, suggesting shared genetic etiologies and possibly linked pathophysiological pathways. Understanding the genetic interplay between ER+BC and EC can enhance strategies for the precise prevention and screening of these prevalent cancers, potentially leading to improved clinical outcomes and management of secondary primary malignancies. |\n| --- |\n| Abbreviations: BC = breast cancer, CI = confidence interval , EC = endometrial cancer, ER+BC = estrogen receptor-positive breast cancer, ER‐BC = estrogen receptor-negative breast cancer, GWAS = genome-wide association studies, IVs = instrumental variables, IVW = inverse-variance weighted, MR = Mendelian randomization, oaBC = over all breast cancer, OR = odds ratio, PR = Progesterone Receptor, SIR = standardized incidence ratios, SNP = single nucleotide polymorphism. |\n| Keywords: bidirectional causal relationship, breast cancer, endometrial cancer, genetics, Mendelian randomization |\n\n1. Introduction  \nDue to lifestyle changes and societal developments, shift in the spectrum of human tumor diseases has  \na significant occurred.[1,2]  \nAccording to recent data from the American Cancer Society, breast cancer (BC) has emerged as the most prevalent malignant tumor, with an estimated 297,790 new cases reported in  \nThis work was supported by the Science and Technology Development Fund, Macau SAR (Nos: 0098/2021/A2 and 0048/2023/AFJ), Macau University of Science and Technology’s Faculty Research Grant (No: FRG-23-003-FC), Chinese Medicine Guangdong Laboratory (No: HQCML-C-2024007), the National Natural Science Foundation of China (grant 82073388 to W-MS, and grant 81871883 to Z-XY), the Affiliated Hospital of Guangdong Medical University Clinical Research Program (LCYJ2020B005 and LCY2022DL002), the Natural Outstanding Youth Fund of Guangdong Province (2022B1515020090), and Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Noncommunicable Diseases (2022B1212030003).  \nThe authors have no conflicts of interest to disclose.  \nThe datasets","cbCaiqEcuoO6TKV9","https://ap.wps.com/l/cbCaiqEcuoO6TKV9","pdf",754891,"English","# Abstract\n# Introduction\n# Abbreviations\n# Keywords","[{\"question\":\"What question does the study address about breast cancer and endometrial cancer?\",\"answer\":\"It examines whether there is a genetic causal relationship between breast cancer (BC) and endometrial cancer (EC), and whether the direction of causality is bidirectional.\"},{\"question\":\"How were genetic instruments and data sources selected?\",\"answer\":\"BC genetic instruments were taken from Breast Cancer Association Consortium GWAS summary statistics, while EC data came from the Endometrial Cancer Association Consortium, the Epidemiology of Endometrial Cancer Consortium, and the UK Biobank.\"},{\"question\":\"Which analytical methods were used to test robustness and validity?\",\"answer\":\"The primary method was inverse-variance weighted, with additional MR-Egger and weighted median analyses. Pleiotropy was assessed using MR-Egger intercept testing, heterogeneity with the Cochrane Q test, and sensitivity with a leave-one-out analysis.\"}]","Investigating the genetic causal relationship between breast cancer and endometrial cancer - A two-sample Mendelian randomization study | PDF",1789998980,18]