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，难以诊断。如果不改进目前的早期检测方案，70%以上被诊断为EOC的妇女将在疾病晚期被发现，生存机会大大降低。有趣的是，肯塔基大学最近的研究表明，被诊断为EOC的受试者与没有EOC的年龄匹配的对照组相比，牙下缺失（缺少1到6颗恒牙）的可能性要高8.1倍。牙齿缺失，可以在9岁时通过牙科诊所的x光片诊断出来，可能是目前已知的最早的EOC风险标志。然而，如果在医学或牙科诊所中仅将下颌缺失作为风险标志，许多妇女可能会付出巨大的代价和焦虑，接受更多的EOC检测，而可能并不真正处于危险之中。如果特定的标记（一个人的遗传密码的变化）能够被识别出来，这些标记更频繁地与下颌骨缺失的EOC患者联系在一起（与健康对照组相比），这些标记可以用于早期筛查患有下颌骨缺失的年轻女性，以确定一生中患EOC风险最高的女性。这可能导致对患EOC风险最高的妇女进行更早的筛查，增加早期诊断的数量，并挽救无数人的生命。这项研究将从肯塔基州中部被诊断为EOC或健康对照组的高加索妇女的唾液中创建一个DNA（遗传密码）资源库。每位受试者的DNA样本将与受试者完整的牙科病史和涵盖三代的广泛的家族病史/癌症病史一起提供。标记（DNA代码的微小变化）将被研究，使用一种称为Taqman基因分型的过程，以确定最常与EOC和下颌畸形受试者相关的标记，而不是与对照组受试者相关的标记。待研究的标记存在于激活素/抑制素和RUNX细胞间信号通路的基因（DNA代码）中。这两种途径在牙齿发育和生殖组织发育和/或维持中起着重要作用。总之，本研究将确定特定的标志物，结合对女性下颌畸形的观察，可以对EOC最高风险个体进行早期筛查，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.