Epithelial ovarian cancer (EOC), known as the silent killer in women, is difficult to diagnosis due to a lack of effective early screening markers for the disease. Without improvements in the current early detection protocols, over 70% of women diagnosed with EOC will be identified in late stage disease with a significantly reduced chance of survival. Interestingly, recent work at the University of Kentucky has demonstrated that subjects diagnosed with EOC were 8.1 times more likely to also have hypodontia, the lack of formation of 1 to 6 permanent teeth, when compared to age-matched control subjects without EOC. Hypodontia, which can be diagnosed as early as age 9 by radiograph in the dental clinic, may be the earliest known marker of EOC- risk today. If hypodontia alone was utilized as a risk marker in the medical or dental clinic, however, many women could undergo increased testing for EOC with great cost and anxiety, and may not truly be at risk. If specific markers (changes in a person's genetic code) could be identified which more frequently associate with EOC patients who have hypodontia (compared to healthy controls) these markers could be utilized for the early screening of young women with hypodontia to identify women at the highest risk for developing EOC in their lifetime. This could lead to earlier screening protocols for women at highest risk of developing EOC, increased numbers of early stage diagnoses, and the saving of countless numbers of lives. This study will create a DNA (genetic code) resource bank from the saliva of a population of Caucasian women in Central Kentucky who have either been diagnosed with EOC or are healthy control subjects. Every subject's DNA sample will be accompanied with the subject's complete dental history and an extensive family medical/cancer history covering three generations. Markers (small changes in the DNA code) will be studies, using a process called Taqman genotyping, to identify markers which most frequently associate with the subjects having EOC and hypodontia but not the control subjects. The markers to be studies are found within genes (DNA code) of the Activin/Inhibin and RUNX cell-to-cell signaling pathways. These two pathways have important roles for tooth development and reproductive tissue development and/or maintenance. In summary, this study will identify specific markers, which when combined with the observation of hypodontia in women, could result in earlier screenings for highest EOC risk individuals, an increase number of early stage diagnoses, and the saving of many lives.

Public Health Relevance

Epithelial Ovarian Cancer (EOC) accounts for 3% of all cancers in women. As the deadliest reproductive system cancer that afflicts women, and the fifth leading cause of death due to cancer in women, it is an important health issue. Less than 20% of all EOC cases are diagnosed in stage I, when the cancer is confined to the ovaries, and the 5 year survival rate is 93%. Without improvements in the current screening methods for early detection, over 70% of women diagnosed with EOC will be diagnosed after the cancer has metastasized (i.e., in Stages III and IV) with 5 year survival rates of only 34% and 18%, respectively. This project will explore the novel observation that missing teeth (teeth that never properly formed) and EOC appear to be associated. We will identify genetic markers, which when combined with the presence of missing teeth, will identify women at greatest risk of developing EOC in their lifetime at much younger ages than previously possible. Identification of these high risk individuals should result in earlier screening regiments for the individuals, an increased number of early stages diagnoses, and the saving of many lives.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Small Research Grants (R03)
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NIDCR Special Grants Review Committee (DSR)
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Harris, Emily L
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University of Kentucky
Schools of Dentistry
United States
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