Are developmentally missing teeth a predictive risk marker of malignant diseases in non-syndromic individuals? A systematic review.

BACKGROUND: Different genes and loci that are associated with non-syndromic developmental tooth agenesis (TA) have the same causation pathway in the development of tumours including breast cancer (BC), epithelial ovarian cancer (EOC), colorectal cancer (CRC) and lung cancer (LC). OBJECTIVES: To assess the link between TA and the development of cancer. SEARCH SOURCES: This registered review included a comprehensive search of electronic databases (Cochrane Central Register of Controlled Trials [CENTRAL], LILACS, Scopus, Web of Science and Medline via Ovid) until 1 April 2020, supplemented by manual, grey literature and reference lists search. There was no restriction in term of date of publication, gender, race or type of hypodontia. DATA SELECTION: The primary outcome was the relationship between TA and cancer. The secondary outcome was to identify the genetic correlation between TA and cancer. DATA EXTRACTION: Study selection, data extraction and risk of bias assessment were performed independently and induplicate by two reviewers, with disputes resolved by a third reviewer. RESULTS: Eight studies with a moderate-high risk of bias were included in the final review, with a total of 5821 participants. Due to the heterogeneity among the included studies, the data were presented narratively. Limited studies reported a high prevalence of EOC (19.2%-20%) and CRC (82%-100%) in individuals with TA (depending on the study) compared to those without TA (3% for EOC and 0% for CRC). While others reported a weak correlation between EOC and CRC and TA (P > 0.05). Weak evidence suggested a strong correlation between breast, cervical uterine and prostate cancers and TA (P < 0.05). CONCLUSIONS: Though low-quality evidence suggests a link between TA and cancer, it was not possible to verify that TA can hold a predictive value as a marker for cancers. Further research is needed to confirm the association. REGISTRATION: PROSPERO (CRD42020139751).