{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T10:14:01Z","timestamp":1788257641651,"version":"build-2803163510"},"reference-count":41,"publisher":"American Medical Association (AMA)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"Importance<\/jats:title>There is some evidence that tooth agenesis (congenital absence of 1 or more teeth) is associated with cancer risk, especially carcinomas of the colon and ovaries, but results of previous studies are conflicting, and associations have not yet been evaluated in a population-based setting.<\/jats:p><\/jats:sec>Objective<\/jats:title>To examine the association between tooth agenesis and specific cancer types before 40 years of age.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>This population-based cohort study used linking data from nationwide registries in Denmark to assess all Danish live-born singletons born from January 1, 1977, to December 31, 2018, and followed up for up to 40 years. Data were analyzed from January through June 2023.<\/jats:p><\/jats:sec>Exposure<\/jats:title>Tooth agenesis as documented by the Danish Central Registry of Odontology (Danish municipal pediatric dental care) from January 1, 1988, to December 31, 2018, and from hospital encounters in the Danish National Patient Registry within the entire study period.<\/jats:p><\/jats:sec>Main Outcome and Measures<\/jats:title>The primary outcome was first cancer diagnosis before 40 years of age obtained from the Danish Cancer Registry. Associations between tooth agenesis and specific cancers were estimated by Cox proportional hazards regression as hazard ratios (HRs) with 95% CIs. Analyses were split into age groups: younger than 1 year, 1 to younger than 3 years, 3 to younger than 10 years, 10 to younger than 20 years, 20 to younger than 30 years, and 30 to younger than 40 years. Associations with nonsyndromic tooth agenesis were evaluated after exclusion of individuals with known syndromes.<\/jats:p><\/jats:sec>Results<\/jats:title>Among 2\u202f501\u202f715 included individuals (1\u202f284\u202f292 [51.3%] male), 70\u202f288 (2.8%) had a diagnosis of tooth agenesis (mean [SD] age at diagnosis, 13.2 [4.1] years) and 26\u202f308 (1.1%) had a diagnosis of early-onset cancer within the study period; 778 individuals had co-occurrence of tooth agenesis and cancer. Overall, tooth agenesis was positively associated with several cancer types, including neuroblastoma (age 1 to &amp;lt;3 years; HR, 4.20; 95% CI, 2.24-7.88), nephroblastoma (age 1 to &amp;lt;3 years; HR, 4.59; 95% CI, 2.37-8.91), hepatoblastoma (age 1 to &amp;lt;3 years; HR, 7.10; 95% CI, 2.70-18.68), osteosarcoma (age 10 to &amp;lt;20 years; HR, 2.19; 95% CI, 1.11-4.32), colorectal carcinomas (age 30 to &amp;lt;40 years; HR, 2.81; 95% CI, 1.38-5.71), and carcinomas of bladder (age 20 to &amp;lt;30 years; HR, 3.35; 95% CI, 1.35-8.30).<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>This cohort study found associations between congenital tooth agenesis and several cancer types, from childhood to early adulthood. Further evaluation of these associations is needed to assess possible clinical implications.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2024.0365","type":"journal-article","created":{"date-parts":[[2024,3,15]],"date-time":"2024-03-15T15:31:22Z","timestamp":1710516682000},"page":"e240365","source":"Crossref","is-referenced-by-count":5,"title":["Congenital Tooth Agenesis and Risk of Early-Onset Cancer"],"prefix":"10.1001","volume":"7","author":[{"given":"Saga Elise","family":"Eiset","sequence":"first","affiliation":[{"name":"Department of Clinical Medicine, Aarhus University, Aarhus, Denmark"},{"name":"Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark"},{"name":"Department of Child and Adolescent Psychiatry, Aarhus University Hospital, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Schraw","sequence":"additional","affiliation":[{"name":"Section of Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gitte Vrelits","family":"S\u00f8rensen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark"},{"name":"Department of Clinical Genetics, Aalborg University Hospital, Aalborg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pernille Ax\u00e9l","family":"Gregersen","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Aarhus University, Aarhus, Denmark"},{"name":"Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark"},{"name":"Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja A.","family":"Rasmussen","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia H.","family":"Ramlau-Hansen","sequence":"additional","affiliation":[{"name":"Department of Public Health\u2013Epidemiology, Aarhus University, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip J.","family":"Lupo","sequence":"additional","affiliation":[{"name":"Section of Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Hasle","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Aarhus University, Aarhus, Denmark"},{"name":"Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2024,3,15]]},"reference":[{"issue":"5","key":"zoi240033r1","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1111\/eos.1980.88.issue-5","article-title":"Hypodontia of permanent teeth in Danish schoolchildren.","volume":"88","author":"R\u00f8lling","year":"1980","journal-title":"Scand J Dent Res"},{"issue":"12","key":"zoi240033r2","doi-asserted-by":"publisher","first-page":"2327","DOI":"10.3390\/genes13122327","article-title":"Molecular pathway-based classification of ectodermal dysplasias: first five-yearly update.","volume":"13","author":"Peschel","year":"2022","journal-title":"Genes (Basel)"},{"issue":"1","key":"zoi240033r3","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1038\/s41368-022-00208-x","article-title":"Tooth number abnormality: from bench to bedside.","volume":"15","author":"Zhang","year":"2023","journal-title":"Int J Oral Sci"},{"issue":"6","key":"zoi240033r4","doi-asserted-by":"publisher","first-page":"2401","DOI":"10.1111\/odi.v29.6","article-title":"Gene mutations and chromosomal abnormalities in syndromes with tooth agenesis.","volume":"29","author":"Lan","year":"2023","journal-title":"Oral Dis"},{"issue":"4","key":"zoi240033r5","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1111\/cge.v99.4","article-title":"Tooth agenesis: what do we know and is there a connection to cancer?","volume":"99","author":"Bonczek","year":"2021","journal-title":"Clin Genet"},{"issue":"5","key":"zoi240033r6","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/j.ejmg.2014.02.013","article-title":"Is there a link between ovarian cancer and tooth agenesis?","volume":"57","author":"Bonds","year":"2014","journal-title":"Eur J Med Genet"},{"issue":"2","key":"zoi240033r7","doi-asserted-by":"publisher","first-page":"163","DOI":"10.14219\/jada.archive.2008.0132","article-title":"Hypodontia as a risk marker for epithelial ovarian cancer: a case-controlled study.","volume":"139","author":"Chalothorn","year":"2008","journal-title":"J Am Dent Assoc"},{"issue":"2","key":"zoi240033r8","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1177\/0022034512468750","article-title":"Tooth agenesis association with self-reported family history of cancer.","volume":"92","author":"K\u00fcchler","year":"2013","journal-title":"J Dent Res"},{"issue":"1","key":"zoi240033r9","doi-asserted-by":"publisher","first-page":"2979","DOI":"10.1038\/s41598-018-21368-z","article-title":"Colorectal cancer-associated genes are associated with tooth agenesis and may have a role in tooth development.","volume":"8","author":"Williams","year":"2018","journal-title":"Sci Rep"},{"issue":"4","key":"zoi240033r10","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1111\/odi.2016.22.issue-4","article-title":"Hypodontia, a prospective predictive marker for tumor?","volume":"22","author":"Yin","year":"2016","journal-title":"Oral Dis"},{"issue":"3","key":"zoi240033r11","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1016\/j.cell.2006.10.018","article-title":"Wnt\/beta-catenin signaling in development and disease.","volume":"127","author":"Clevers","year":"2006","journal-title":"Cell"},{"issue":"5","key":"zoi240033r12","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1086\/386293","article-title":"Mutations in AXIN2 cause familial tooth agenesis and predispose to colorectal cancer.","volume":"74","author":"Lammi","year":"2004","journal-title":"Am J Hum Genet"},{"issue":"11","key":"zoi240033r13","doi-asserted-by":"publisher","first-page":"1382","DOI":"10.5858\/arpa.2018-0570-RA","article-title":"Familial adenomatous polyposis syndrome: an update and review of extraintestinal manifestations.","volume":"143","author":"Dinarvand","year":"2019","journal-title":"Arch Pathol Lab Med"},{"issue":"9596","key":"zoi240033r14","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.1016\/S0140-6736(07)61602-X","article-title":"The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies.","volume":"370","author":"von Elm","year":"2007","journal-title":"Lancet"},{"issue":"1","key":"zoi240033r15","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1007\/s10654-018-0356-1","article-title":"The Danish Medical Birth Register.","volume":"33","author":"Bliddal","year":"2018","journal-title":"Eur J Epidemiol"},{"issue":"8","key":"zoi240033r16","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1007\/s10654-014-9930-3","article-title":"The Danish Civil Registration System as a tool in epidemiology.","volume":"29","author":"Schmidt","year":"2014","journal-title":"Eur J Epidemiol"},{"issue":"1","key":"zoi240033r17","first-page":"15","article-title":"Dental anomalies in the primary dentition: distribution and correlation with the permanent dentition.","volume":"21","author":"Nik-Hussein","year":"1996","journal-title":"J Clin Pediatr Dent"},{"key":"zoi240033r19","doi-asserted-by":"publisher","first-page":"449","DOI":"10.2147\/CLEP","article-title":"The Danish National Patient Registry: a review of content, data quality, and research potential.","volume":"7","author":"Schmidt","year":"2015","journal-title":"Clin Epidemiol"},{"issue":"7","key":"zoi240033r20","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1177\/1403494810393562","article-title":"The Danish Cancer Registry.","volume":"39","author":"Gjerstorff","year":"2011","journal-title":"Scand J Public Health"},{"issue":"2","key":"zoi240033r21","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1111\/cge.1979.15.issue-2","article-title":"Electronic data processing in the Danish cytogenetic central register and EDP problems of registers in general.","volume":"15","author":"Videbech","year":"1979","journal-title":"Clin Genet"},{"issue":"7","key":"zoi240033r22","doi-asserted-by":"publisher","first-page":"121","DOI":"10.21037\/atm","article-title":"Time-varying covariates and coefficients in Cox regression models.","volume":"6","author":"Zhang","year":"2018","journal-title":"Ann Transl Med"},{"issue":"1","key":"zoi240033r24","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/1897-4287-12-7","article-title":"Colorectal cancer and self-reported tooth agenesis.","volume":"12","author":"Lindor","year":"2014","journal-title":"Hered Cancer Clin Pract"},{"issue":"5","key":"zoi240033r25","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1016\/j.bpg.2005.06.003","article-title":"Neuroendocrine tumours (carcinoids) of the appendix.","volume":"19","author":"Stinner","year":"2005","journal-title":"Best Pract Res Clin Gastroenterol"},{"issue":"8","key":"zoi240033r26","doi-asserted-by":"publisher","first-page":"3615","DOI":"10.1007\/s00423-022-02639-w","article-title":"Low-grade mucinous neoplasms (LAMN) of the appendix in Germany between 2011 and 2018: a nationwide analysis based on data provided by the German Center for Cancer Registry Data (ZfKD) at the Robert Koch Institute (RKI).","volume":"407","author":"K\u00f6hler","year":"2022","journal-title":"Langenbecks Arch Surg"},{"issue":"2","key":"zoi240033r27","doi-asserted-by":"publisher","first-page":"531","DOI":"10.3390\/ijms22020531","article-title":"Lynch syndrome: its impact on urothelial carcinoma.","volume":"22","author":"Lindner","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"1","key":"zoi240033r28","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1093\/geronb\/gbv112","article-title":"Your face is your fortune: does adolescent attractiveness predict intimate relationships later in life?","volume":"72","author":"Karraker","year":"2017","journal-title":"J Gerontol B Psychol Sci Soc Sci"},{"issue":"4","key":"zoi240033r29","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.v65.4","article-title":"Germline APC mutations in hepatoblastoma.","volume":"65","author":"Yang","year":"2018","journal-title":"Pediatr Blood Cancer"},{"issue":"2","key":"zoi240033r30","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1007\/s10689-017-0035-5","article-title":"Dental anomalies in pediatric patients with familial adenomatous polyposis.","volume":"17","author":"Septer","year":"2018","journal-title":"Fam Cancer"},{"issue":"15","key":"zoi240033r31","doi-asserted-by":"publisher","first-page":"3751","DOI":"10.3390\/ijms20153751","article-title":"New insights about the Wnt\/\u00df-Catenin signaling pathway in primary bone tumors and their microenvironment: a promising target to develop therapeutic strategies?","volume":"20","author":"Danieau","year":"2019","journal-title":"Int J Mol Sci"},{"key":"zoi240033r32","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.bone.2016.10.017","article-title":"Molecular genetics of osteosarcoma.","volume":"102","author":"Rickel","year":"2017","journal-title":"Bone"},{"issue":"3","key":"zoi240033r33","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1002\/pbc.24842","article-title":"A systematic review of dental late effects in survivors of childhood cancer.","volume":"61","author":"Gawade","year":"2014","journal-title":"Pediatr Blood Cancer"},{"issue":"2","key":"zoi240033r34","first-page":"98","article-title":"Rhabdomyosarcoma of the head and neck in children.","volume":"19","author":"Radzikowska","year":"2015","journal-title":"Contemp Oncol (Pozn)"},{"key":"zoi240033r35","doi-asserted-by":"publisher","first-page":"563","DOI":"10.2147\/CLEP","article-title":"The Danish health care system and epidemiological research: from health care contacts to database records.","volume":"11","author":"Schmidt","year":"2019","journal-title":"Clin Epidemiol"},{"issue":"4","key":"zoi240033r36","doi-asserted-by":"publisher","first-page":"291","DOI":"10.3109\/00016357.2015.1119306","article-title":"Prevalence, risk surfaces and inter-municipality variations in caries experience in Danish children and adolescents in 2012.","volume":"74","author":"N\u00f8rrisgaard","year":"2016","journal-title":"Acta Odontol Scand"},{"issue":"4","key":"zoi240033r37","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1111\/ipd.2012.22.issue-4","article-title":"Microdontia and hypodontia of premolars and permanent molars in childhood cancer survivors after chemotherapy.","volume":"22","author":"Pedersen","year":"2012","journal-title":"Int J Paediatr Dent"},{"issue":"5","key":"zoi240033r38","doi-asserted-by":"publisher","first-page":"810","DOI":"10.2319\/112813-876.1","article-title":"Hypodontia prevalence and pattern in women with epithelial ovarian cancer.","volume":"84","author":"Fekonja","year":"2014","journal-title":"Angle Orthod"},{"issue":"4","key":"zoi240033r39","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1007\/s10689-021-00283-9","article-title":"Rare germline variants in the AXIN2 gene in families with colonic polyposis and colorectal cancer.","volume":"21","author":"Chan","year":"2022","journal-title":"Fam Cancer"},{"issue":"3","key":"zoi240033r40","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1007\/s10689-021-00280-y","article-title":"Familial colorectal cancer and tooth agenesis caused by an AXIN2 variant: how do we detect families with rare cancer predisposition syndromes?","volume":"21","author":"Jensen","year":"2022","journal-title":"Fam Cancer"},{"issue":"3","key":"zoi240033r41","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1007\/s10689-019-00120-0","article-title":"Phenotypic confirmation of oligodontia, colorectal polyposis and cancer in a family carrying an exon 7 nonsense variant in the AXIN2 gene.","volume":"18","author":"Beard","year":"2019","journal-title":"Fam Cancer"},{"key":"zoi240033r18","unstructured":"Det Koordinerende Organ for Registerforskning. Sundhedsstyrelsens Centrale Odontologiske Register. Accessed January 19, 2024. https:\/\/sundhedsdatastyrelsen.dk\/da\/registre-og-services\/om-de-nationale-sundhedsregistre\/graviditet-foedsler-og-boern\/boern_ungdom_tandpleje"},{"key":"zoi240033r23","unstructured":"Therneau T, Crowson C, Atkinson E. Using Time Dependent Covariates and Time Dependent Coefficients in the Cox Model. Accessed January 19, 2024. https:\/\/cran.r-project.org\/web\/packages\/survival\/vignettes\/timedep.pdf"}],"container-title":["JAMA Network Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/articlepdf\/2816220\/eiset_2024_oi_240033_1709923046.62605.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,15]],"date-time":"2024-03-15T15:31:27Z","timestamp":1710516687000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/fullarticle\/2816220"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,15]]},"references-count":41,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,3,4]]}},"URL":"https:\/\/doi.org\/10.1001\/jamanetworkopen.2024.0365","relation":{},"ISSN":["2574-3805"],"issn-type":[{"value":"2574-3805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,15]]}}}