Tooth agenesis tied to early-onset cancer in early childhood and early adulthood: JAMA

"Our population-based cohort study of 2.5 million live-born singletons with up to 40 years of follow-up showed that tooth agenesis was positively associated with several cancer types, including nephroblastoma, neuroblastoma, and hepatoblastoma in childhood; osteosarcoma in adolescence; and carcinomas of the bladder and colorectal carcinomas in young adulthood," the researchers reported.

Previous studies have provided some evidence that tooth agenesis (congenital absence of one or more teeth) is associated with cancer risk, particularly carcinomas of the ovaries and colon, but these results are conflicting, and associations have not been evaluated yet in a population-based setting. To fill this knowledge gap, Saga Elise Eiset, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark, and colleagues aimed to investigate the association between tooth agenesis and specific cancer types before 40 years of age.

For this purpose, the researchers used linking data from nationwide registries in Denmark to evaluate all Danish live-born singletons born from 1977 to 2018 and followed for up to 4 years. Data analysis was done from January through June 2023.

Exposure was tooth agenesis as documented by the Danish Central Registry of Odontology from 1988 to 2018, and from hospital encounters in the Danish National Patient Registry within the entire study period.

The study's primary outcome was the first cancer diagnosis before 40 years of age obtained from the Danish Cancer Registry. Cox proportional hazards regression as hazard ratios (HRs) estimated associations between tooth agenesis and specific cancers. 

Analyses were divided into age groups: younger than 1 year, 1 to younger than three 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. After excluding individuals with known syndrome, associations with nonsyndromic tooth agenesis were evaluated.

The study led to the following findings:

• Among 2 501 715 included individuals (51.3% male), 2.8% had a diagnosis of tooth agenesis (mean age at diagnosis, 13.2 years), and 1.1% had a diagnosis of early-onset cancer within the study period; 778 individuals had co-occurrence of tooth agenesis and cancer.
• Tooth agenesis was positively associated with several cancer types, including nephroblastoma (age 1 to <3 years; HR, 4.59), neuroblastoma (age 1 to <3 years; HR, 4.20), osteosarcoma (age 10 to <20 years; HR, 2.19), hepatoblastoma (age 1 to <3 years; HR, 7.10), colorectal carcinomas (age 30 to <40 years; HR, 2.81), and carcinomas of bladder (age 20 to <30 years; HR, 3.35).

In conclusion, the cohort study supports previous evidence indicating an association between tooth agenesis and the risk of colorectal cancer in early adulthood. The findings also suggest associations with several other specific cancer types, in particular, extracranial embryonal tumors in childhood. However, within the study period, there was a low absolute number of tooth agenesis–cancer co-occurrences.

"An improved understanding of the genetic causes of the specific associations is needed to assess possible clinical implications," the researchers wrote.

Reference:

Eiset SE, Schraw J, Sørensen GV, et al. Congenital Tooth Agenesis and Risk of Early-Onset Cancer. JAMA Netw Open. 2024;7(3):e240365. doi:10.1001/jamanetworkopen.2024.0365