Genetic Markers Associated with Epithelial Ovarian Cancer and Hypodontia

描述（由申请人提供）：上皮性卵巢癌（EOC），被称为女性的沉默杀手，由于缺乏有效的早期筛查标志物而难以诊断。如果不改进目前的早期检测方案，超过70%的被诊断患有EOC的妇女将在晚期疾病中被发现，生存机会显着降低。有趣的是，肯塔基州大学最近的研究表明，与年龄匹配的无EOC对照组相比，诊断为EOC的受试者患缺牙（1至6颗恒牙未形成）的可能性高出8.1倍。牙齿发育不全最早可在9岁时通过牙科诊所的X光片诊断，可能是目前已知的最早的EOC风险标志。然而，如果在医疗或牙科诊所中仅将缺牙作为风险标志，许多妇女可能会接受更多的EOC检测，费用高昂，焦虑不安，可能不会真正处于风险之中。如果特定的标志物（一个人的遗传密码的变化），可以确定更频繁地与EOC患者谁有缺牙（与健康对照组相比），这些标志物可以用于早期筛查年轻女性缺牙，以确定妇女在其一生中发展EOC的风险最高。这可能会导致早期筛查方案的妇女在发展EOC的最高风险，增加早期诊断的数量，并挽救无数的生命。这项研究将从肯塔基州中部的一群白人妇女的唾液中创建一个DNA（遗传密码）资源库，这些妇女被诊断患有EOC或为健康对照受试者。每例受试者的DNA样本将随附受试者完整的牙科病史和涵盖三代人的广泛家族病史/癌症史。将使用称为Taqman基因分型的过程来研究标记物（DNA密码中的小变化），以鉴定最常与患有EOC和缺牙的受试者而不是对照受试者相关的标记物。待研究的标志物存在于激活素/抑制素和RUNX细胞间信号传导途径的基因（DNA代码）中。这两种途径对牙齿发育和生殖组织发育和/或维持具有重要作用。总之，这项研究将确定特定的标志物，当与女性缺牙的观察相结合时，可能会导致早期筛查最高EOC风险的个体，增加早期诊断的数量，并挽救许多生命。

DESCRIPTION (provided by applicant): 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.