Genetic Markers Associated with Epithelial Ovarian Cancer and Hypodontia

与上皮性卵巢癌和牙齿发育不全相关的遗传标记

• 批准号: 8030355
• 负责人: Lorri A. Morford
• 金额: $ 11.14万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8030355
• 关键词: Accounting; Activins; Affect; Age; Alleles; Anxiety; Cancer Patient; Caucasians; Caucasoid Race; Cause of Death; Cells; Cessation of life; Code; Collection; DNA; Dental; Dental Clinics; Development; Diagnosis; Disease; Disease Marker; Early Diagnosis; Eligibility Determination; Epithelial ovarian cancer; Family; Female; Foundations; Future; Generations; Genes; Genetic Code; Genetic Markers; Genotype; Health; High Risk Woman; Hypodontia; Individual; Kentucky; Lead; Maintenance; Malignant Female Reproductive System Neoplasm; Malignant Neoplasms; Malignant neoplasm of ovary; Medical; Methods; Nature; Neoplasm Metastasis; Oral health; Ovarian Tissue; Ovary; Pathway interactions; Persons; Population; Process; Protocols documentation; Recording of previous events; Reproductive system; Research; Resources; Risk; Risk Marker; Role; Saliva; Sampling; Screening procedure; Shapes; Signal Pathway; Signal Transduction; Single Nucleotide Polymorphism; Staging; Survival Rate; Symptoms; Testing; Time; Tissues; Tooth structure; Universities; Variant; Woman; Women' s Health; Work; aged; base; cancer risk; cost; genetic association; high risk; inhibin; novel; outcome forecast; permanent tooth; reproductive development

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. 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.

描述（由申请人提供）：由于缺乏对该疾病的有效的早期筛查标记，因此很难诊断上皮卵巢癌（EOC），被称为女性沉默杀手。如果没有改善当前的早期检测方案，将在晚期疾病中确定超过70％的被诊断为EOC的妇女的生存机会大大减少。有趣的是，肯塔基大学最近的工作表明，与没有EOC的年龄匹配的对照对象相比，被诊断为EOC的受试者的低牙齿可能性也高出8.1倍，缺乏1至6个恒牙。牙科诊所的射线照相最早可以在9岁时诊断出的下降症可能是当今EOC风险的最早标志。但是，如果仅将下降症用作医疗或牙科诊所中的风险标志，但是，许多妇女可能会以巨大的成本和焦虑进行EOC的测试增加，并且可能不会真正面临风险。如果可以确定特定的标记（与健康对照组相比）更频繁地与患有低牙本质的EOC患者相关的特定标记（遗传代码的变化），则可以将这些标记物用于早期筛查患有低牙齿的年轻女性，以鉴定出在其生命周期中发育EOC的最高风险的女性。这可能会导致较早的EOC风险最高风险的妇女筛查方案，增加的早期诊断数量以及挽救无数生命的延长。这项研究将从肯塔基州中部的一群高加索妇女的唾液中创建一个DNA（遗传密码）资源库，她们要么被诊断出患有EOC，要么是健康的对照受试者。每个受试者的DNA样本都将伴随该受试者的完整牙科病史，并拥有涵盖三代人的广泛家庭医学/癌症史。标记（DNA代码中的小变化）将使用称为Taqman基因分型的过程进行研究，以识别与具有EOC和降低的受试者相关的标记，但不是对照对象。在激活素/抑制素和Runx细胞到细胞信号通路的基因（DNA代码）中发现了要研究的标记。这两种途径在发育和生殖组织发育和/或维持方面具有重要作用。总而言之，这项研究将确定特定的标记，当这些标记与女性低下的观察相结合时，可能会导致更早的EOC风险个人的筛查，增加的早期诊断数量以及挽救许多生命。 公共卫生相关性：上皮卵巢癌（EOC）占女性所有癌症的3％。作为困扰女性的最致命的生殖系统癌症，也是妇女癌症导致的第五个主要死亡原因，这是一个重要的健康问题。当癌症局限于卵巢时，所有EOC病例中只有不到20％被诊断出来，而5年生存率为93％。没有改善当前筛查方法的早期检测方法，在癌症转移（即在III阶段和IV阶段）中，将诊断出超过70％的EOC妇女，分别仅5年生存率为34％和18％。该项目将探讨缺失的牙齿（从未正确形成的牙齿）和EOC似乎相关的新发现。我们将确定遗传标志物与缺失牙齿的存在相结合时，将确定女性在年轻的年龄较大的一生中发育最大的EOC风险，而不是以前。这些高风险个人的识别应导致对个人的早期筛查团，诊断的早期诊断数量增加，并挽救了许多生命。