Tooth agenesis as a potential clinical indicator of colorectal cancer susceptibility: a systematic review.

BACKGROUND: Tooth agenesis, including hypodontia and oligodontia, is one of the most common developmental dental anomalies. Emerging evidence suggests a potential association between tooth agenesis and colorectal cancer (CRC), particularly in the context of shared genetic pathways such as WNT signalling and AXIN2 mutations. However, findings across epidemiological and genetic studies remain inconsistent. OBJECTIVE: To evaluate the current evidence regarding the association between tooth agenesis and colorectal cancer, with emphasis on epidemiological trends, genetic susceptibility, and clinical implications. METHODOLOGY: A systematic review of recent observational, cohort, and genetic studies investigating the relationship between tooth agenesis and CRC was conducted. Studies assessing prevalence, risk estimates (HR, OR), and genetic variants, particularly AXIN2 mutations were analyzed. Both statistically significant and non-significant findings were considered to provide a balanced synthesis of the literature. RESULTS: Recent large-scale cohort data suggest a positive association between tooth agenesis and early-onset CRC, with increased hazard ratios reported in specific age groups. Strong genetic associations have been identified between pathogenic AXIN2 variants, oligodontia, and colorectal polyposis/CRC. Conversely, some case-control studies found no statistically significant difference in the prevalence of missing teeth between CRC patients and controls. Overall, evidence indicates that while tooth agenesis is not a universal risk marker for CRC, specific genetic subgroups may present substantially increased risk. CONCLUSION: Current evidence supports a potential association between tooth agenesis, particularly oligodontia linked to AXIN2 mutations and colorectal neoplasia. Although not all studies demonstrate significant epidemiological correlations, genetic findings highlight important clinical implications. Tooth agenesis should not be used for universal screening; targeted AXIN2 testing in patients with polyposis and tooth agenesis is a reasonable interim approach, pending larger prospective studies with standardised methods. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/register/TemplatePreview, identifier CRD420251231764.