A research group at the University of Helsinki, Finland, has found a gene defect that causes hereditary colorectal cancer and defects in dentition. The finding was published online on March 23 in the American Journal of Human Genetics.

The groups led by professors Sinikka Pirinen and Irma Thesleff at the Institute of Dentistry and Institute of Biotechnology of the University of Helsinki are working on the genetic basis of hereditary dental aberrations .

The group identified a mutation in the gene AXIN2 in a Finnish family with severe lack of teeth. AXIN2 is known as a modulator of Wnt signalling which is one of the key signal pathways regulating embryonic development. The specific roles of AXIN2 during development have, however, not been known, and its essential role for the development of teeth was also previously unknown.

Congenital absence of a few teeth is rather common and it is usually not associated with any other health problem. However, in this family the individuals who lacked teeth were also diagnosed to have neoplastic changes in the colon. The neoplasias ranged from polyps to precancerous lesions and cancer. Those members of the family who did not have the mutation did neither have defects in teeth nor neoplastic changes in colon.

The patients who had the mutation lacked 8 to 27 permanent teeth, thus in the most severe cases almost all permanent teeth were missing. Defects in the deciduous dentition were observed in only one patient. A different mutation in AXIN2 was found in an unrelated patient who also lacked several permanent teeth.

It is interesting that one gene mutation causes both tooth agenesis and predisposes to colorectal cancer. The finding underlines the concept that same genes act in normal and malignant development.

On the other hand, the connection between tooth agenesis and cancer raises the question whether tooth agenesis could be used as an indication for cancer susceptibility. The results so far show that mutations in AXIN2 are responsible for only a small proportion of tooth agenesis, and that they may be limited to severe forms. The researchers now plan to evaluate the existence of the connection between tooth agenesis and cancer on a population level.

More information: Pekka Nieminen, tel. +358 -9-19125215,
e-mail: pekka.nieminen@helsinki.fi