Association of Tooth Agenesis and Cancer

Abstract

Source: Küchler EC, Lips A, Tannure PN, et al. Tooth agenesis association with self-reported family history of cancer. J Dent Res. 2013; 92(2): 149– 155; doi: 10.1177/0022034512468750Investigators from the University of Pittsburgh and Brazil conducted a case-control study to determine if tooth agenesis, also known as developmental absence of teeth or hypodontia, is associated with a self-reported family history of cancer. Participants were recruited during dental visits at the Federal University of Rio de Janeiro. Cases were individuals with tooth agenesis in permanent teeth assessed visually and by radiograph. Controls did not have tooth agenesis and were matched 4:1 with cases by age, ethnicity, and social-cultural background. All participants completed a structured questionnaire regarding demographic information and family history of cancer in first- or second-degree relatives. Buccal cell samples were also collected from all participants for genotyping assays of genes associated with cleft lip and palate and cancer (FGF3, FGF10, FGFR2, and AXIN2). Investigators recorded the number and type of missing teeth in cases and calculated the risk of a child with tooth agenesis having at least 1 family member with cancer. They also assessed the risk of certain genotypes in children with tooth agenesis.There were 82 cases and 328 controls. The number of missing teeth in cases ranged from 1 to >6. Premolar teeth were the most frequently missing. Cases were significantly more likely to have a self-reported family history of cancer than controls (OR = 2.7), particularly with respect to cancers involving the brain/nervous system (OR = 12.4), breast (OR = 2.9), and prostate (OR = 3.5). Genotype analysis showed significant associations between AXIN2 and FGF3 and lower incisor agenesis, between FGF3 and upper lateral incisor agenesis, and between FGF10 and all types of tooth agenesis. A polymorphism in FGFR2 was significantly more common in cases with premolar agenesis than in controls (OR = 1.8).The investigators conclude that tooth agenesis and cancer share a similar genetic background that includes FGF3, FGF10, FGFR2, and AXIN2 genes.Dr Slayton has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.Hypodontia is a condition that is easily determined by clinical and/or radiographic examination by a dentist and has a prevalence in the general population of about 5% (excluding wisdom teeth).1 If this dental anomaly is associated with a family history of cancer, it could conceivably serve as a risk marker for the condition.Case and control selection is crucial in a study of tooth agenesis because teeth are frequently lost for other reasons, such as trauma, dental caries, or periodontal disease. In the current study, the mean age of patients who were cases was 18 years old, which is important because this is an age when the development of all permanent teeth is evident either clinically or radiographically. The family history of cancer was limited to first-and second-degree relatives, increasing the likelihood of accurate reporting. Although self-report has the potential for being inaccurate and causing misclassification of cancer, it is likely to result in underreporting rather than overreporting and to be similar for both cases and controls.It should be noted that both cases and controls were recruited from the same dental clinic in an effort to have participants in each group with similar ethnic, social, and cultural backgrounds. It is also important to note that the genes selected for this study were chosen based on previous studies demonstrating an association with either tooth agenesis or cancer.2,3 The gene AXIN2, involved in cell growth, proliferation, and differentiation, has also been shown to be associated with agenesis of lower incisors.4The clinical relevance of this study should be interpreted with caution. First, individuals are not always aware that they have developmentally missing teeth, so it may not be ascertained in a thorough medical history. Second, physicians may not have access to intraoral radiographic findings and will need to rely on self-report or clinical examination to confirm the presence of hypodontia. Third, although this study demonstrated a significant association between hypodontia and a family history of cancer, it is unclear what the risk of cancer is for the index case. Therefore, counseling patients regarding the potential risk for cancer in the future would be premature.