Epigenetic alterations in oral rinse as biomarkers of oral and pharyngeal cancer

口腔冲洗液的表观遗传改变作为口腔癌和咽癌的生物标志物

基本信息

批准号：
8581752
负责人：
Scott M. Langevin
金额：
$ 10.31万
依托单位：
UNIVERSITY OF CINCINNATI
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-25 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8581752
关键词：
Accounting Affect Area Attention Bioinformatics Biological Assay Biological Markers Boston Breathing Cancer Patient Case-Control Studies Collection Complex CpG dinucleotide Critiques Cytosine DNA Methylation DNA Sequence DNA Transposable Elements Defect Deglutition Detection Development Development Plans Diagnosis Diagnostic Disease Disease Outcome Early Diagnosis Eating Epigenetic Process Epithelium Funding Gene Expression Genome Stability Genomics Goals Head and Neck Cancer Impairment Individual K22 Award Literature Maintenance Malignant Neoplasms Malignant neoplasm of pharynx Measurement Modification Molecular Molecular Epidemiology Molecular Epidemiology of Cancer Morbidity - disease rate Mouth Neoplasms Oral Oropharyngeal Outcome Palpation Patients Pharyngeal Neoplasms Population Primary Neoplasm Process Prognostic Marker Public Health Publishing Recurrence Relative (related person)Reporting Research Research Personnel Research Project Grants Resources Risk Sampling Second Primary Cancers Social Impacts Solid Neoplasm Stage at Diagnosis Staging Techniques Training Training Activity Translational Research Treatment Cost Treatment Failure Tumor Tissue Uncertainty United States National Institutes of Health Upper aerodigestive tract cancer Visual Writing advanced disease base burden of illness cancer diagnosis carcinogenesis career career development case control clinical application clinically relevant design disease diagnosis economic impact epigenetic marker epigenome experience follow-up gene repression high risk interest malignant mouth neoplasm meetings men methyl group mortality novel novel diagnostics outcome forecast pharynx squamous cell carcinoma population based programs public health relevance pyrosequencing research and development sample collection screening tool tumor

项目摘要

DESCRIPTION (provided by applicant): The focus of my research is the molecular epidemiology of upper aerodigestive tract cancers; with a primary interest in the epigenetics of cancer, in particular DNA methylation, and its diagnostic and prognostic biomarker applications. My current research has concentrated on use of an array-based approach for the identification of DNA methylation markers for head and neck cancer. My career goal is to develop an externally funded research program and establish myself as an independent academic investigator in the field of molecular cancer epidemiology. To facilitate this progression, I am proposing the following translational research and career development plan through the NCI K22 Career Transition mechanism. Oral & pharyngeal cancer accounted for an estimated 39,400 new cancer diagnoses in 2011, with 7,900 people dying of the disease. The prognosis is relatively poor, with an overall 5-year survival around 60% that worsens with increasing stage at diagnosis. Oral & pharyngeal cancers have among the highest risk of 2nd primary cancer of all solid tumors, along with a very high rate of disease recurrence, which are a major reason for treatment failure. Additionally, oral & pharyngeal cancer patients frequently suffer from high morbidity, including disfigurement and impairment of basic functions, such as talking, swallowing, eating and breathing. Much recent cancer biomarker research has focused on epigenetic alterations, with particular attention paid to DNA methylation due to its relative stability and amenability to measurement. Currently, no proven screening techniques are in wide-spread use for oral & pharyngeal cancer aside from visual inspection and palpation. Use of oral rinse as a non-invasive technique for sample collection may have utility in detection of DNA methylation in oral & pharyngeal cancers and therefore has potential in biomarker-based clinical applications. Hence, this proposal seeks to apply an epigenome-wide array-based approach to oral rinse samples to identify novel DNA methylation markers of oral & pharyngeal cancer that can facilitate early diagnosis and predict disease outcome (including survival and risk of recurrence or development of a 2nd primary) using the existing population resources of a large case-control study of head and neck cancer. Further, to progress to research independence in the highly complex field of molecular cancer epidemiology, I will require additional training and experience conducting bioinformatic analyses and lab-based molecular techniques for epigenetic analysis, in particular design and conduct of pyrosequencing assays. I also need to gain key experience in the comprehensive management of an NIH funded research project in molecular cancer epidemiology. This K22 award will afford me the opportunity to obtain the necessary experience and further develop these areas through formal and informal training activities (including additional biostatistical coursework), which are crucial to my transition to he independent stage of my research career in molecular cancer epidemiology.

描述（由申请人提供）：我的研究的重点是上层气管癌的分子流行病学；对癌症表观遗传学的主要兴趣，特别是DNA甲基化及其诊断和预后生物标志物的应用。我目前的研究集中在使用基于阵列的方法来鉴定头颈癌的DNA甲基化标记。我的职业目标是制定一项由外部资助的研究计划，并确立自己是分子癌流行病学领域的独立学术研究者。为了促进这种进步，我通过NCI K22职业过渡机制提出以下转化研究和职业发展计划。 2011年，口腔和咽癌估计估计有39,400次新的癌症诊断，其中7,900人死于该疾病。预后相对较差，总5年生存率约为60％，随着诊断阶段的增加而恶化。口腔和咽癌具有所有实体瘤的第二个原发性癌症的最高风险，以及疾病复发率很高，这是治疗衰竭的主要原因。此外，口腔和咽癌患者经常患有高发病率，包括对基本功能的毁容和损害，例如说话，吞咽，饮食和呼吸。最近的许多癌症生物标志物研究都集中在表观遗传学的改变上，由于其相对稳定性和测量能力，特别注意DNA甲基化。目前，除了视觉检查和触诊外，没有经过验证的筛查技术可用于口腔和咽癌。将口服冲洗作为样品收集的非侵入性技术可能具有检测口腔和咽癌中DNA甲基化的实用性，因此在基于生物标志物的临床应用中具有潜力。因此，该提议试图采用基于表观基因组阵列的口服冲洗样品的方法，以鉴定口腔和咽癌的新型DNA甲基化标志物，可以使用大型病例和颈部癌症的现有种群的人群资源的现有种群资源和颈部癌症的现有人群资源来促进早期诊断和预测疾病的结果（包括复发和复发或第二个初级的发展）。此外，为了研究分子癌流行病学高度复杂领域的独立性，我将需要进行进一步的培训和经验，以进行生物信息学分析和基于实验室的分子技术，以进行表观遗传学分析，特别是焦磷酸测定法的设计和行为。我还需要在NIH资助的分子癌流行病学研究项目的综合管理方面获得关键经验。这项K22奖将使我有机会获得必要的经验，并通过正式和非正式的培训活动（包括额外的生物统计学课程）进一步发展这些领域，这对于我过渡到我在分子癌的研究职业的独立阶段至关重要。