‘Plausible’ link may exist between congenitally missing teeth and early-onset cancer
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Key takeaways:
- Tooth agenesis may be associated with multiple cancer types in children and young adults.
- Further research is needed to determine whether certain cancers and tooth agenesis have a shared genetic cause.
Individuals with tooth agenesis may be more likely to develop several different cancer types from childhood through young adulthood, according to results published in JAMA Network Open.
The population-based cohort study out of Denmark found higher rates of neuroblastoma, nephroblastoma, hepatoblastoma, osteosarcoma, colorectal carcinomas, carcinomas of the bladder, as well as other cancers, in individuals at various age ranges up to 40 years of age.
“Our study is hypothesis-generating, and further research is needed to evaluate the possible clinical implications,” Saga E. Eiset, MD, a physician in the department of pediatrics and adolescent medicine at Aarhus University Hospital in Denmark, told Healio. “However, I think this is a reminder that physicians should also look for dental anomalies when performing a dysmorphology assessment.”
Background and methodology
Previous reports have suggested that tooth agenesis, the congenital absence of one or more teeth, could be associated with various cancers due to signaling pathways essential to tooth formation also having a role in cancer development, according to background information provided by researchers.
“The hypothesis is not new but had not yet been investigated in a population-based setting,” Eiset said. “In Denmark, we have several population-based registries with many years of high-quality data, including a public dental registry. This was a unique opportunity to investigate the tooth agenesis–cancer hypothesis.”
Eiset and colleagues investigated single births in Denmark between 1977 and 2018 to evaluate for any association between tooth agenesis and specific cancer types.
They used multiple registries to gather data on tooth agenesis (not including third molars) and cancer diagnoses.
The study cohort consisted of 2,501,715 individuals (51.3% men; 2.8% had tooth agenesis; 1.1% had early-onset cancer diagnosis), with 778 having both tooth agenesis and cancer.
Results and next steps
Tooth agenesis showed associations with any cancer in individuals aged 1-3 years (HR = 2.23; 95% CI, 1.77-2.81) and 30-40 years (HR = 1.2; 95% CI, 1.02-1.4).
Children between 1-3 years old had links to numerous specific cancers, including acute myeloid leukemia (HR = 3.52; 95% CI, 1.61-7.67), neuroblastoma (HR = 4.2; 95% CI, 2.24-7.88), nephroblastoma and other nonepithelial kidney tumors (HR = 4.59; 95% CI, 2.37-8.91), hepatoblastoma (HR = 7.1; 95% CI, 2.7-18.68) and rhabdomyosarcoma (HR = 8.67; 95% CI, 3.98-18.92).
Study patients between 3-6 years old also showed higher risk for acute myeloid leukemia (HR = 3.82; 95% CI, 1.35-10.8) and rhabdomyosarcoma (HR = 3.46; 95% CI, 1.37-8.72).
Individuals between 10-20 years old had increased risk for osteosarcoma (HR = 2.19; 95% CI, 1.11-4.32).
Young adults between 20-30 years old had higher risk for carcinomas of the appendix (HR = 2.54; 95% CI, 1.03-6.24) and bladder (HR = 3.35; 95% CI, 1.35-8.3).
Researchers also reported an association between patients aged 30-40 years old and colorectal carcinomas (HR = 2.81; 95% CI, 1.38-5.71).
“While we expected to find an association with colorectal cancers, other findings were surprising,” Eiset said.
“It is likely that some of the associations we have found are chance findings, as we made multiple comparisons in our analysis,” she added. “However, some findings were novel but biologically plausible, such as the association between tooth agenesis and hepatoblastoma, which is known to be related to the APC gene, which in turn is also known to be associated with tooth anomalies.”
However, despite these results, Eiset stressed the risk for cancer in individuals with tooth agenesis is low.
“In general, people with tooth agenesis should not worry,” Eiset said. “Tooth agenesis is a very common condition, whereas in absolute numbers, there were few cancer cases in our study. Even if you are at six or eight times increased risk for developing a certain cancer, six or eight times a very rare event is still very rare.”
Limitations of the study included the registration-based approach, which helped build a large cohort but offered no proof of cause, and the possible misdiagnosis of tooth agenesis in children under 6 years old who received previous cancer therapy that may impact their oral health.
“We hypothesize that the co-occurrence of cancers and tooth agenesis found in our study could have a shared genetic cause,” Eiset said. “If we can narrow this down to one or a few known or novel cancer genes, then we can evaluate if genetic screening and/or cancer surveillance is beneficial for some individuals with tooth agenesis. Characterizing the genetic pathways of cancer development is also the basis for targeted cancer treatment.”
For more information:
Saga E. Eiset, MD, can be reached at sagmar@rm.dk.
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