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Using 250,015 East Asians from Biobank Japan and 377,441 Europeans from UK Biobank, the study identifies ten cancer risk variants, including pleiotropic loci. Quantifying shared heritability detects positive genetic correlations between breast and prostate cancer across populations. Large-scale breast/prostate analyses reveal 91 newly significant loci, with pathway and cell-type enrichment indicating common genetic components.",{"@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":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/pan-cancer-and-cross-population-genome-wide-association-studies-dissect-shared-genetic-backgrounds-underlying-carcinogenesis/377970/",{"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/pan-cancer-and-cross-population-genome-wide-association-studies-dissect-shared-genetic-backgrounds-underlying-carcinogenesis/377970.png","ImageObject",300,407,{"name":92,"@type":93},"Jake","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What datasets and populations were used for the pan-cancer GWAS meta-analysis?","Question",{"text":112,"@type":113},"The study combines 250,015 East Asians from Biobank Japan and 377,441 Europeans from UK Biobank, covering 13 cancers, with replication studies included.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How many cancer risk variants and pleiotropic associations were identified?",{"text":117,"@type":113},"Ten cancer risk variants are identified, including five pleiotropic associations that link specific loci to multiple cancers.",{"name":119,"@type":110,"acceptedAnswer":120},"Which cancer pair showed positive shared genetic correlations across populations?",{"text":121,"@type":113},"Breast and prostate cancer show positive genetic correlations, validated in both Biobank Japan and UK Biobank and further confirmed using FinnGen.","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},377970,1790309191,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":39,"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":145},962084928904,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Article [https://doi.org/10.1038/s41467-023-39136-7](https://doi.org/10.1038/s41467-023-39136-7)  \nPan-cancer and cross-population genomewide association studies dissect shared genetic backgrounds underlying carcinogenesis  \nReceived: 16 September 2022  \n\n| Accepted: 31 May 2023 |\n| --- |\n| |\n| Check for updates |\n\nGo Sato1,2, Yuya Shirai1,3,4, Shinichi Namba 1, Ryuya Edahiro1,3,  \nKyuto Sonehara1,5,6, Tsuyoshi Hata2, Mamoru Uemura2, the Biobank Japan Project*, Koichi Matsuda 7, Yuichiro Doki2, Hidetoshi Eguchi2 &  \nYukinori Okada 1,4,5,6   \nIntegrating genomic data of multiple cancers allows de novo cancer grouping and elucidating the shared genetic basis across cancers. Here, we conduct the pan-cancer and cross-population genome-wide association study (GWAS) meta-analysis and replication studies on 13 cancers including 250,015 East Asians (Biobank Japan) and 377,441 Europeans (UK Biobank). We identify ten cancer risk variants including five pleiotropic associations (e.g., rs2076295 at DSP on 6p24 associated with lung cancer and rs2525548 at TRIM4 on 7q22 nominally associated with six cancers). Quantifying shared heritability among the cancers detects positive genetic correlations between breast and prostate cancer across populations. Common genetic components increase the statistical power, and the large-scale meta-analysis of 277,896 breast/prostate cancer cases and 901,858 controls identifies 91 newly genome-wide significant loci. Enrichment analysis of pathways and cell types reveals shared genetic backgrounds across said cancers. Focusing on genetically correlated cancerscan contribute to enhancing our insights into carcinogenesis.  \nCancer is a leading cause of death worldwide, it kills 10 million people every year, and a rapidly growing burden1. As well as environmental and somatic factors, hereditary components play an important role in cancer development. Genome-wide association studies (GWAS) have detected hundreds of genetic variants associated with specific cancer risk and pleiotropic associations with different cancers, including 2q33 (CASP8-ALS2CR12)2,3, 5p15 ( TERT-CLPTM1L)4,5 and 8q246,7. Analyzing  \ngenomic data of multiple cancers to elucidate pleiotropy and genetic correlations provides opportunities for de novo cancer grouping and highlighting the common mechanisms underlying cancer etiology8.  \nA previous cross-cancer GWAS meta-analysis of five cancers using data from consortia such as the Genetic Associations and Mechanisms in Oncology (GAME-ON) Network, has applied a subset-based approach9 and identified a pleiotropic association at 1q22 involving  \n1Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan. 2Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan. 3Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Japan. 4Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Suita, Japan. 5Laboratory for Systems Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan. 6Department of Genome Informatics, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan. 7Laboratory of Clinical Genome Sequencing, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, the University of Tokyo, Tokyo, Japan. *A list of authors and their affiliations appears at the end of the paper.  \ne-mail: [yokada@sg.med.osaka-u.ac.jp](yokada@sg.med.osaka-u.ac.jp)  \nbreast and lung squamous cell carcinoma10. Previous studies have estimated genetic correlations among cancer pairs and detected genetically correlated cancer pairs. One study including 13 cancers found four pairs with marginally significant correlations11. Lindströmet al. found significant correlations between pancreatic and colorectal cancer, and lung and colorectal cancer12. In another study conducted by Jiang et al","cbCaimAghgWHrDVs","https://ap.wps.com/l/cbCaimAghgWHrDVs","pdf",1743028,11,"English","# Pan-cancer and cross-population GWAS\n## Study design and cohorts\n## Variant discovery and pleiotropy\n## Shared heritability and genetic correlations\n## Large-scale breast/prostate loci and enrichment","[{\"question\":\"What datasets and populations were used for the pan-cancer GWAS meta-analysis?\",\"answer\":\"The study combines 250,015 East Asians from Biobank Japan and 377,441 Europeans from UK Biobank, covering 13 cancers, with replication studies included.\"},{\"question\":\"How many cancer risk variants and pleiotropic associations were identified?\",\"answer\":\"Ten cancer risk variants are identified, including five pleiotropic associations that link specific loci to multiple cancers.\"},{\"question\":\"Which cancer pair showed positive shared genetic correlations across populations?\",\"answer\":\"Breast and prostate cancer show positive genetic correlations, validated in both Biobank Japan and UK Biobank and further confirmed using FinnGen.\"}]","Pan-cancer and cross-population genome-wide association studies dissect shared genetic backgrounds underlying carcinogenesis | PDF",1790227850,28]