Tooth agenesis: What do we know and is there a connection to cancer?

To gain more insight into the prevalence of dental agenesis. Data from Caucasian populations in North America, Australia and Europe were included in a meta-analysis. For the prevalence of African American, Chinese and Arab groups only indications could be reported because of a limited number of studies. Agenesis differs by continent and gender: the prevalence for both sexes was higher in Europe (males 4.6%; females 6.3%) and Australia (males 5.5%; females 7.6%) than for North American Caucasians (males 3.2%; females 4.6%). In addition, the prevalence of dental agenesis in females was 1.37 times higher than in males. The mandibular second premolar was the most affected tooth, followed by the maxillary lateral incisor and the maxillary second premolar. The occurrence of dental agenesis was divided into three main groups: common (P2(i) > I2(s) > P2(s)), less common (I1(i) > I2(i) & P1(s) > C(s) & M2(i)) and rare (M2(s) & M1(s) > C(i) > M1(i) & I1(s)). Unilateral occurrence of dental agenesis is more common than bilateral occurrence. However, bilateral agenesis of maxillary lateral incisors is more common than unilateral agenesis. The overall prevalence of agenesis in the maxilla is comparable with that in the mandible, but a marked difference was found between both jaws regarding tooth type. Absence of one or two permanent teeth is found in 83% of the subjects with dental agenesis. A practical application of the results of the meta-analysis is the estimation of dental treatment need. Copyright Blackwell Munksgaard, 2004

Wnt signaling regulates embryonic pattern formation and morphogenesis of most organs. Aberrations of regulation of Wnt signaling may lead to cancer. Here, we have used positional cloning to identify the causative mutation in a Finnish family in which severe permanent tooth agenesis (oligodontia) and colorectal neoplasia segregate with dominant inheritance. Eleven members of the family lacked at least eight permanent teeth, two of whom developed only three permanent teeth. Colorectal cancer or precancerous lesions of variable types were found in eight of the patients with oligodontia. We show that oligodontia and predisposition to cancer are caused by a nonsense mutation, Arg656Stop, in the Wnt-signaling regulator AXIN2. In addition, we identified a de novo frameshift mutation 1994-1995insG in AXIN2 in an unrelated young patient with severe tooth agenesis. Both mutations are expected to activate Wnt signaling. The results provide the first evidence of the importance of Wnt signaling for the development of dentition in humans and suggest that an intricate control of Wnt-signal activity is necessary for normal tooth development, since both inhibition and stimulation of Wnt signaling may lead to tooth agenesis. Our findings introduce a new gene for hereditary colorectal cancer and suggest that tooth agenesis may be an indicator of cancer susceptibility.