Research Focus

Dr. James K Hartsfield, Jr. and Dr. Lorri A. Morford run the Hereditary Genomics Laboratory within the Center for Oral Health Research in the UK College of Dentistry. A central theme to their research is the study of genomic and genetic markers in genetic association and genetic linkage analyses. In addition to their own studies, Drs. Hartsfield and Morford have welcomed collaborations with other investigators desiring to explore the discovery and investigation of genetic factors associated with other research pertaining to normal growth and pathology in dentistry and/or medicine. One of their primary research interests is the investigation of the common underlying genetic factors for dental agenesis and cancer susceptibility (particularly epithelial ovarian and colon). In other collaborative efforts, they are also interested in the investigation of genetic factors involved in (1) familial non-medullary thyroid cancer and (2) HPV and oral cancer. Primary Research Theme: Epithelial Ovarian Cancer (EOC) is a devastating disease affecting women. It is the deadliest reproductive system cancer that afflicts women, and is the fifth leading cause of cancer-related death in females. Individuals who develop EOC do not experience “hallmark” early disease symptoms, and consistent pre-malignancy markers are minimal (i.e. family history, BRCA gene mutations, etc.). This inability to easily detect early stages of disease often leads to delays in diagnosis, advanced stage disease, and poor prognoses. Less than 20% of all EOC cases are diagnosed in stage I (non-metastatic) where the 5 year survival rate is 93%. Without improvements in methods to identify and screen high risk EOC populations, over 70% of women will be diagnosed in metastatic stages III and IV, where the 5 year survival rates are only 34% and 18%, respectively. In a preliminary work by Dr Leigh Chalathorn in the Orthodontic Division of the UK College of Dentistry, it was shown that women diagnosed with EOC are 8.1 times more likely to also have hypodontia (1 to 6 naturally missing teeth) compared to controls. This is not trivial, as 20% of the women diagnosed with EOC in the study had hypodontia and/or small teeth, compared to only 3% in the control population. Of the EOC patients with hypodontia, 60% had a family history of hypodontia, while only 30% of the same EOC/hypodontia patients had a family history of ovarian cancer. By comparison, control subjects with hypodontia had no family history of hypodontia or family history of EOC. At the time, this finding marked the second report in the literature of tooth agenesis occurring with cancer. In the work of Dr. Lammi and colleagues, an association was previously observed with colon cancer, severe tooth agenesis (oligodontia) and mutations in the AXIN2 gene. Thus, if genetic markers could be identified linking the presence of EOC with hypodontia, it may be possible to use these markers clinically (similar to markers for BRCA1/2) to pre-screen cancer-free woman with hypodontia for heightened risk of EOC development. Women positive for both hypodontia and the genetic marker(s) could be placed on early cancer screening regiments, potentially improving the rate of early stage diagnosis significantly. This research of Drs. Hartsfield and Morford is funded by an R03 Grant from the National Institute of Dental and Craniofacial Research (NIDCR) and is being conducted in collaboration with Dr. Chris DeSimone (UK College of Medicine) and Dr. Dave Fardo (UK College of Public Health).

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