[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-333520-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-333520-en":131},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","somatic-mutations-in-keap1-nrf2-complex-in-breast-cancer","Somatic Mutations in KEAP1-NRF2 Complex in Breast Cancer","","Breast cancer remains the leading cause of cancer deaths for women, and long-term estrogen exposure is implicated in carcinogenesis through semiquinone production and impaired detoxification. The study focuses on cytoprotection-related metabolic regulator polymorphisms, including KEAP1 and NRF2 variants, to understand individual oxidative-stress responses. Researchers genotyped these polymorphisms in blood, tumor tissue, and surrounding tissue, identifying somatic mutations and correlating findings with prognostic clinicopathological features. A total of 23 controls and 69 women with histologically confirmed breast cancer were enrolled, and DNA was genotyped from blood, surrounding, and tumor samples. Genotype distributions differed for rs35652124 between tissue compartments and were associated with histological grade patterns, including higher variability in grade 2 and evidence of loss of heterozygosity in surrounding tissue. The results suggest a heterogeneous, active microenvironment influencing breast cancer outcomes, supporting further evaluation of histologic grade 2 predictive value using somatic mutation profiles.",{"@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/somatic-mutations-in-keap1-nrf2-complex-in-breast-cancer/333520/",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/somatic-mutations-in-keap1-nrf2-complex-in-breast-cancer/333520.png","ImageObject",300,407,{"name":42,"@type":43},"Violet","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-11-01","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",11,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What is the main research aim of the study?","Question",{"text":63,"@type":64},"To genotype KEAP1 and NRF2 metabolic regulator polymorphisms in blood, tumors, and surrounding tissues, identify somatic mutations, and correlate them with prognostic clinicopathological features.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"Which participant groups and samples were analyzed?",{"text":68,"@type":64},"The study recruited 23 controls and 69 women with histologically confirmed breast cancer and genotyped DNA obtained from blood, surrounding tissue, and tumor tissue.",{"name":70,"@type":61,"acceptedAnswer":71},"What did the researchers find regarding tissue-specific genotype distributions?",{"text":72,"@type":64},"rs35652124 showed different genotype distribution between blood/surrounding tissue versus tumor/surrounding tissues, and other polymorphisms varied in distribution across tissues when considering histological grade.","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},333520,1790194720,{"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":140,"language":141,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":12,"update_tm":145,"read_time":146,"preview_page_count":4},4398048950312,"https://ap-avatar.wpscdn.com/avatar/400002538284de19e3c?_k=1778320343897328908","cancers   \nArticle  \nSomatic Mutations in KEAP1-NRF2 Complex in Breast Cancer  \nMicaela Almeida 1,2,3,*, Catarina L. Ferreira 1,2, Rosa Maria Tomé 2,4, José Fonseca-Moutinho 1,2,4, António Polónia 3,5, Ana Cristina Ramalhinho 1,2,4 and Luiza Breitenfeld 1,2  \nCitation: Almeida, M.; Ferreira, C.L.; Tomé, R.M.; Fonseca-Moutinho, J.; Polónia, A.; Ramalhinho, A.C.; Breitenfeld, L. Somatic Mutations in KEAP1-NRF2 Complex in Breast Cancer. Cancers 2024, 16, 2411 . [https://doi.org/10.3390/cancers](https://doi.org/10.3390/cancers)[ ](https://doi.org/10.3390/cancers)16132411  \nAcademic Editor: Christos Papadimitriou  \nReceived: 6 June 2024  \nRevised: 26 June 2024  \nAccepted: 28 June 2024  \nPublished: 29 June 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Health Sciences Research Centre (CICS), Faculty of Health Sciences, University of Beira Interior (UBI), Avenida Infante D. Henrique, 6200-506 Covilhã, Portugal; [cferreira@fcsaude.ubi.pt](cferreira@fcsaude.ubi.pt) (C.L.F.); [jafmoutinho@fcsaude.ubi.pt](jafmoutinho@fcsaude.ubi.pt) (J.F.-M.); [luiza@ubi.pt](luiza@ubi.pt) (L.B.)  \n2 Clinical Academic Centre of Beiras (CACB), Edifício UBImedical, Estrada Municipal 506, 6200 Covilhã, Portugal; [rosatome@chcbeira.min-saude.pt](rosatome@chcbeira.min-saude.pt)  \n3 Department of Pathology, Ipatimup Diagnostics, Rua Júlio Amaral de Carvalho, 45, 4200-135 Porto, Portugal; [apolonia@ipatimup.pt](apolonia@ipatimup.pt)  \n4 Cova da Beira Local Health Unit, Alameda Pêro da Covilhã, 6200-251 Covilhã, Portugal  \n5 Escola de Medicina e Ciências Biomédicas, Instituto de Investigação, Inovação e Desenvolvimento, Fundação Fernando Pessoa (FP-I3ID), Avenida Fernando Pessoa, 150, 4420-096 Gondomar, Portugal  \n* [Correspondence: malmeida@fcsaude.ubi.pt](Correspondence: malmeida@fcsaude.ubi.pt)  \nSimple Summary: Breast cancer remains a burden for women worldwide. Among the factors that contribute to breast cancer development is estrogen exposure during one’s lifetime, both endocrine and exocrine. Polymorphisms in KEAP1-NRF2 complex, the master regulator of oxidative stress metabolism, have been correlated with a poorer outcome. The aim of our study was to identify and correlate polymorphisms in this complex, in breast cancer tissue, benign surrounding tissue and in peripheral blood. We verified a tendency towards the loss of heterozygosity in the benign surrounding tissue when compared to blood and to tumour tissue. Correlating with clinical data, histologic grade 2 has a higher variability of genotypes. The results indicate a heterogeneous and active microenvironment. Therefore, clinical approaches would benefit from the evaluation of somatic mutations in this complex. Moreover, further studies should be developed in order to evaluate the predictive value of the histologic grades, taking into consideration the genetic profile.  \nAbstract: Breast cancer remains the leading cause of cancer deaths for women. Long-term estrogen exposure is considered carcinogenic due to semiquinone production and to compromised detoxification. Metabolic regulator polymorphisms, such as KEAP1 (rs1048290) and NRF2 (rs35652124, rs6721961, rs6706649), can be valuable in understanding the individual cytoprotection profile. Thus, we aim to genotype these polymorphisms in blood, tumours and surrounding tissue, to identify somatic mutations and correlate it to prognoses. A total of 23 controls and 69 women with histological confirmed breast cancer were recruited, and DNA from blood/surrounding/tumour tissue was genotyped. Genotyping and clinicopathological data were correlated. We verified that rs35652124 presents different genotype distribution between the blood/surround","cbCaikvGnuPufoHs","https://ap.wps.com/l/cbCaikvGnuPufoHs","pdf",444780,14,"English","# Introduction\n## Study rationale and estrogen-related carcinogenesis\n## Genetic alterations and oxidative stress pathways\n# Objectives and study design\n## Participant recruitment and sample collection\n## Genotyping strategy and clinicopathological correlation\n# Results\n## Genotype distribution differences across tissue compartments\n## Loss of heterozygosity and histological grade variability\n# Discussion\n## Implications for breast cancer microenvironment and outcome\n## Future directions for predictive evaluation","[{\"question\":\"What is the main research aim of the study?\",\"answer\":\"To genotype KEAP1 and NRF2 metabolic regulator polymorphisms in blood, tumors, and surrounding tissues, identify somatic mutations, and correlate them with prognostic clinicopathological features.\"},{\"question\":\"Which participant groups and samples were analyzed?\",\"answer\":\"The study recruited 23 controls and 69 women with histologically confirmed breast cancer and genotyped DNA obtained from blood, surrounding tissue, and tumor tissue.\"},{\"question\":\"What did the researchers find regarding tissue-specific genotype distributions?\",\"answer\":\"rs35652124 showed different genotype distribution between blood/surrounding tissue versus tumor/surrounding tissues, and other polymorphisms varied in distribution across tissues when considering histological grade.\"}]","Somatic Mutations in KEAP1-NRF2 Complex in Breast Cancer | PDF",1790002868,35]