Investigating the association of ovarian disease with tooth agenesis

OBJECTIVES: Patients with epithelial ovarian cancer and ovarian cysts have been found to have a higher prevalence of congenital tooth agenesis than the general population. A common genetic factor may predispose women to both tooth agenesis and susceptibility to ovarian disease in analogy to gene mutations in AXIN2, which result in tooth agenesis and predisposition to colon cancer. We have begun to assess the correlation of ovarian disease and tooth agenesis by sequence analysis of several genes that are known to be involved in tooth development and are also expressed in the female reproductive system and/or tumors.

METHODS: Buccal swab samples from 50 ovarian cancer and 10 ovarian cyst patients with and without tooth agenesis as well as samples from tooth agenesis probands without ovarian problems were subjected to whole genome amplification in order to obtain sufficient DNA for further analysis. So far major portions of the PAX9, MSX1, AXIN2, EDA, BARX1 and BARX2 genes have been PCR amplified and sequenced.

RESULTS: No mutations have yet been identified in any of the genes analyzed. Several common polymorphisms like 34Ala>Gly in MSX1 exon 1 and a double polymorphism in the third exon of PAX9 are being investigated for allele frequencies in different groups. In addition, we have found several new polymorphisms in adjacent intron sequences, which will be further explored.

CONCLUSION: Our preliminary data suggest that mutations in the coding areas of PAX9, MSX1, AXIN2, EDA, BARX1 and BARX2 are not involved in the pathogenesis of the combined ovarian/dental symptoms in these patients. In the future, other genes that are expressed during tooth development may serve as candidates for analysis.

This work was supported by Baylor Oral health Foundation (SPW), funds from College of Dentistry, Lexington UK for LC and CB, and NIH U24-PEI6472 (RDS).