{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,5]],"date-time":"2026-04-05T07:56:47Z","timestamp":1775375807023,"version":"3.50.1"},"reference-count":71,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T00:00:00Z","timestamp":1757635200000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Orofacial clefts (OFCs) are among the most common craniofacial birth defects and have been investigated for possible associations with increased cancer risk in affected individuals and their families.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>This narrative review synthesizes current evidence from epidemiological, familial, and genetic studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Population\u2010based and registry analyses have reported elevated risks of breast, brain, lung, oral, colorectal, and hematologic cancers, while meta\u2010analyses highlight inconsistent findings and frequent null associations. Familial clustering studies provide stronger support, with excess colorectal and gastric cancers observed in <jats:italic>AXIN2<\/jats:italic>\u2010 and <jats:italic>CDH1<\/jats:italic>\u2010positive pedigrees and an increased prevalence of cancer among relatives of non\u2010syndromic cleft lip and palate patients. At the genetic level, variants in <jats:italic>AXIN2<\/jats:italic>, <jats:italic>CDH1<\/jats:italic>, <jats:italic>FOXE1<\/jats:italic>, <jats:italic>BRCA1<\/jats:italic>\/2, <jats:italic>BRIP1<\/jats:italic>, and <jats:italic>E2F1<\/jats:italic> have been implicated in both craniofacial development and tumorigenesis. Evidence also points to the modifying role of environmental exposures, particularly maternal smoking, which may interact with susceptibility variants to amplify risk. Current research is limited by small sample sizes, subtype heterogeneity, and underrepresentation of late\u2010onset cancers. Larger, subtype\u2010specific studies integrating genomic and environmental data are needed to clarify risk pathways and guide the development of targeted screening strategies for individuals with OFCs and their families.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdr2.2528","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T09:21:15Z","timestamp":1757668875000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cancer Risk and Genetic Associations in Individuals With Cleft Lip and Palate and Their Families: A Narrative Review"],"prefix":"10.1002","volume":"117","author":[{"given":"Cesar","family":"Ghadbane","sequence":"first","affiliation":[{"name":"Faculty of Medicine and Medical Sciences University of Balamand  Tripoli Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisia","family":"Maalouf","sequence":"additional","affiliation":[{"name":"Faculty of Medicine 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