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Methods A two-sample Mendelian randomization study used genome-wide association study data on serum H. pylori IgG as exposure and GWAS tumor data (268 benign and malignant tumors) as outcome, followed by discovery/validation analyses. Sensitivity and meta-analysis evaluated robustness and effect integration. Results suggested protective effects on specific benign tumors and potential positive links for certain malignancies in single cohorts, with no major heterogeneity or pleiotropy. Conclusion Findings support a causal association and possible protective role in some benign extragastric tumors.",{"@graph":69,"@context":127},[70,84,106],{"@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/helicobacter-pylori-infection-is-causally-associated-with-extra-gastric-tumors-a-mendelian-randomization-study/353614/",{"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/helicobacter-pylori-infection-is-causally-associated-with-extra-gastric-tumors-a-mendelian-randomization-study/353614.png","ImageObject",300,407,{"name":92,"@type":93},"Hazel","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",16,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119,123],{"name":110,"@type":111,"acceptedAnswer":112},"What is the main research question of the study?","Question",{"text":113,"@type":114},"The study assesses whether Helicobacter pylori infection has a causal association with extra-gastric tumors, addressing uncertainty beyond observational evidence.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How were data sources and variables defined in the Mendelian randomization analysis?",{"text":118,"@type":114},"Serum H. pylori IgG levels from GWAS served as the exposure, while GWAS data covering 268 benign and malignant tumors served as the outcome; SNPs were drawn from OpenGWAS/GWAS Catalog and FinnGen.",{"name":120,"@type":111,"acceptedAnswer":121},"What did the results show across discovery and validation cohorts?",{"text":122,"@type":114},"The study found negative causal effects of H. pylori infection on certain benign tumors (cranial nerves and extrahepatic bile ducts) in both cohorts, while several potentially positive associations were observed only in a single cohort.",{"name":124,"@type":111,"acceptedAnswer":125},"How did the study check whether the findings were robust and not distorted by bias?",{"text":126,"@type":114},"Sensitivity analyses evaluated heterogeneity and horizontal pleiotropy for significant MR directions, and meta-analysis integrated findings from both cohorts to confirm the protective effects on relevant benign tumors.","https://schema.org",{"og:url":83,"og:type":129,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":131,"canonical":83},"index,follow",{"doc_id":133,"site_id":62},353614,1790174358,{"code":4,"msg":5,"data":136},{"doc_id":133,"user_id":137,"nickname":92,"user_avatar":138,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":139,"file_id":140,"file_url":141,"file_type":142,"file_size":143,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":144,"language":145,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":146,"faqs":147,"seo_title":148,"seo_description":67,"update_tm":149,"read_time":150},137441390410,"https://ap-avatar.wpscdn.com/avatar/2000252f4ab5702993?_k=1776741390130283984","Liu et al. Discover Oncology (2026) 17:211 [https://doi.org/10.1007/s12672-025-04178-4](https://doi.org/10.1007/s12672-025-04178-4)  \nDiscover Oncology  \nANALYSIS Open Access  \nHelicobacter pylori infection is causally associated with extra-gastric tumors: a Mendelian randomization study  \nJianwei Liu1*, Haiqiang Cheng2 and Gege Feng3*  \n*Correspondence: Jianwei Liu [liujianwei567@163.com](liujianwei567@163.com)  \nGege Feng [gegefeng0407@163.com](gegefeng0407@163.com)[ ](gegefeng0407@163.com)1Department of Gastroenterology, Qilu Hospital (Qingdao) of Shandong University, Hefei Road, Qingdao 266000, Shandong, China 2School of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei, China 3Department of Hematology, Qilu Hospital of Shandong University, Wenhuaxi Road, Jinan 250012, Shandong, China  \nAbstract  \nBackground Helicobacter pylori (H. pylori) infection is a major pathogen associated with gastric cancer. However, the causal relationship between H. pylori infection and extra-gastric tumors has not been fully elucidated.  \nMethods A two-sample Mendelian randomization (MR) study was conducted  \nusing genome-wide association study (GWAS) data on serum H. pylori IgG levels as the exposure variable and GWAS data on 268 benign and malignant tumors asthe outcome variable. Single nucleotide polymorphisms (SNPs) associated with the exposure were identified from the OpenGWAS and GWAS Catalog databases, while those linked to the outcome were sourced from the FinnGen database. Independent MR analyses were performed on the discovery and validation cohorts. Sensitivity analyses, including heterogeneity and pleiotropy assessments, were conducted to ensure the robustness of the results. Meta-analysis was used to integrate significant findings from both cohorts.  \nResults Our findings demonstrated negative causal effects of H. pylori infection on benign neoplasms of cranial nerves and extrahepatic bile ducts in both discovery and validation cohorts. Moreover, we found a potentially positive causal link between H. pylori infection and certain malignancies of the hypopharynx, kidney, lip, brain, pancreas, and neuroendocrine system, as well as malignant immunoproliferative diseases and leukemia, although these results were only observed in a single cohort. Sensitivity analyses showed no significant heterogeneity or horizontal pleiotropy in the significant MR directions, supporting the reliability of the results. Meta-analysis further confirmed the protective effect of H. pylori infection on benign cranial nerve and extrahepatic bile duct tumors.  \nConclusion This study revealed that H. pylori infection is causally associated with extragastric tumors, suggesting a potential protective role of H. pylori infection in certain benign tumors.  \nKeywords Helicobacter pylori, Extra-gastric tumors, Mendelian randomization  \n© The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/l](http://creativecommons.org/l)icenses/by-nc-nd/4.0/.  \n1 Introduction  \nHelicobacter pylori (H. pylori) is a Gram","cbCaihGIkJdg7KcZ","https://ap.wps.com/l/cbCaihGIkJdg7KcZ","pdf",2786089,15,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusion\n# Introduction","[{\"question\":\"What is the main research question of the study?\",\"answer\":\"The study assesses whether Helicobacter pylori infection has a causal association with extra-gastric tumors, addressing uncertainty beyond observational evidence.\"},{\"question\":\"How were data sources and variables defined in the Mendelian randomization analysis?\",\"answer\":\"Serum H. pylori IgG levels from GWAS served as the exposure, while GWAS data covering 268 benign and malignant tumors served as the outcome; SNPs were drawn from OpenGWAS/GWAS Catalog and FinnGen.\"},{\"question\":\"What did the results show across discovery and validation cohorts?\",\"answer\":\"The study found negative causal effects of H. pylori infection on certain benign tumors (cranial nerves and extrahepatic bile ducts) in both cohorts, while several potentially positive associations were observed only in a single cohort.\"},{\"question\":\"How did the study check whether the findings were robust and not distorted by bias?\",\"answer\":\"Sensitivity analyses evaluated heterogeneity and horizontal pleiotropy for significant MR directions, and meta-analysis integrated findings from both cohorts to confirm the protective effects on relevant benign tumors.\"}]","Helicobacter pylori infection is causally associated with extra-gastric tumors: a Mendelian randomization study | PDF",1790106362,38]