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This narrative review synthesizes evidence across common hereditary cancer syndromes and highlights that mixed cancer syndromes—especially Li-Fraumeni, Lynch, and hereditary breast and ovarian cancer—plus pathogenic ATM and CHEK2 variants may predispose individuals. It recommends dermatologic evaluation and individualized UV-protection strategies to reduce risk and enable early detection.",{"@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/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/skin-cancer-risk-in-hereditary-mixed-cancer-syndromes/455863/",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/skin-cancer-risk-in-hereditary-mixed-cancer-syndromes/455863.png","ImageObject",300,407,{"name":42,"@type":43},"Sophia Brooks","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-31","2026-09-30",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",9,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What is the focus of the review on skin cancer risk?","Question",{"text":63,"@type":64},"The review examines skin cancer risks across prevalent hereditary mixed cancer syndromes and how genetic mechanisms and underreporting may affect recognition of skin cancers.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"Which hereditary syndromes are highlighted as potentially predisposing to skin cancers?",{"text":68,"@type":64},"The review emphasizes mixed cancer syndromes, especially Li-Fraumeni syndrome, Lynch syndrome, and hereditary breast and ovarian cancer syndrome, and also notes pathogenic ATM and CHEK2 variants.",{"name":70,"@type":61,"acceptedAnswer":71},"What recommendations does the review make for managing skin cancer risk?",{"text":72,"@type":64},"It recommends dermatologic evaluation and individualized UV protection strategies for patients with the reviewed hereditary cancer syndromes to reduce risk and support early detection.","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},455863,1790818403,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,119,122,126],{"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":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":145,"preview_page_count":4},962084925636,"https://ap-avatar.wpscdn.com/davatar_994ba38a5ba835b3df7d355c54d3ed8d","Nikkola et al. Hereditary Cancer in Clinical Practice (2026) 24:1  \n[https://doi.org/10.1186/s13053-025-00326-7](https://doi.org/10.1186/s13053-025-00326-7)  \nHereditary Cancer in Clinical Practice  \nREVIEW Open Access  \nSkin cancer risk in hereditary mixed cancer syndromes  \nVeera Nikkola 1,2,3*, Anna Alakoski3, Jukka-Pekka Mecklin4,7, ToniT. Seppälä5, Jussi Nikkola5,6 and Kashmintan Schrader 1,2  \nAbstract  \nHereditary cancer syndromes are genetic conditions that increase an individual’s risk for multiple cancer types, often due to mutations that affect critical cellular processes such as DNA repair and cell cycle regulation. Skin cancers, including malignant melanoma (MM), basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and related precancerous lesions may be underrecognized in some hereditary cancer syndromes, as suggested by underlying biological mechanisms and their underreporting in studies. In this narrative review, we examine the skin cancer risks associated with the most prevalent hereditary cancer syndromes, including Li-Fraumeni syndrome (LFS), Lynch syndrome (LS), hereditary breast and ovarian cancer syndrome (HBOC), ATM-associated hereditary cancer syndrome, CHEK2-associated hereditary cancer syndrome, BRIP1-associated cancer predisposition, and hereditary leiomyomatosis and renal cell carcinoma (HLRCC) . This review consolidates existing evidence and suggests that mixed cancer syndromes, especially LFS, LS, and HBOC but also pathogenic ATM and CHEK2 variants may predispose individuals to skin cancers, warranting tailored screening and preventive measures. On the basis of emerging evidence, we recommend dermatologic evaluation and individualized UV protection strategies for patients with reviewed hereditary cancer syndromes to reduce skin cancer risk and enhance early detection. Keywords Hereditary cancer syndromes, Hereditary skin cancer, Germline cancer susceptibility mutations, Genetic cancer predisposition, Skin cancer screening  \n*Correspondence:  \nVeera Nikkola  \n[veera.k.nikkola@gmail.com](veera.k.nikkola@gmail.com)  \n1Hereditary Cancer Program, BC Cancer, 600 West 10th Avenue, Vancouver, Canada  \n2Department of Medical Genetics, University of British Columbia, Vancouver, Canada  \n3Department of Dermatology, Tampere University Hospital, Tampere, Finland  \n4Department of Education and Research, The Wellbeing Services County of Central Finland, Jyväskylä, Finland  \n5Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Centre, Tampere, Finland  \n6Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, Canada  \n7Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland  \nIntroduction  \nThe presence of multiple cancers in an individual or family, especially at a young age, suggests an underlying genetic cause [1]. In this review, we use the term hereditary mixed cancer syndrome to describe conditions that extend beyond a single tumor type and involve primarily non-cutaneous cancers, while acknowledging their genetic and biological heterogeneity. This terminology is intended to distinguish these syndromes from primarily cutaneous cancer syndromes, such as CDKN2A-related melanoma predisposition, oculocutaneous albinism, and basal cell nevus syndrome, which have been extensively reviewed elsewhere [2, 3]. Hereditary mixed cancer syndromes involve genetic predispositions to multiple cancer types, often due to mutations in genes involved in  \n© Crown 2025. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, 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 changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, u","cbCairUTHTIHHIiv","https://ap.wps.com/l/cbCairUTHTIHHIiv","pdf",2344237,13,"English","# Abstract\n# Introduction\n## Hereditary mixed cancer syndromes and genetic heterogeneity\n## Classification of genetic variants by ACMG\n## Skin cancer categories and UVR-driven mechanisms\n## Progression and clinical features of cutaneous malignancies\n# Correspondence and author affiliations","[{\"question\":\"What is the focus of the review on skin cancer risk?\",\"answer\":\"The review examines skin cancer risks across prevalent hereditary mixed cancer syndromes and how genetic mechanisms and underreporting may affect recognition of skin cancers.\"},{\"question\":\"Which hereditary syndromes are highlighted as potentially predisposing to skin cancers?\",\"answer\":\"The review emphasizes mixed cancer syndromes, especially Li-Fraumeni syndrome, Lynch syndrome, and hereditary breast and ovarian cancer syndrome, and also notes pathogenic ATM and CHEK2 variants.\"},{\"question\":\"What recommendations does the review make for managing skin cancer risk?\",\"answer\":\"It recommends dermatologic evaluation and individualized UV protection strategies for patients with the reviewed hereditary cancer syndromes to reduce risk and support early detection.\"}]","Skin cancer risk in hereditary mixed cancer syndromes | PDF",1790744528,33]