Molecular Basis of Young Onset Colorectal Cancer

描述(申请人提供)：癌症预防、控制和控制中心 人口科学职业发展奖将提供一个优秀的 我有机会学习进行高质量培训所需的技能 结直肠癌防治研究。我提出的计划是 旨在扩大我们对分子机制的基本理解 潜在的结直肠癌发生，特别是在年轻发病时 人口。我计划收集和描述200名参与者的肿瘤 发病年轻(50岁以下)的结直肠癌(CRC)和200 发病年龄较大的CRC患者。《儿童权利公约》的这一特定部分负担 除了15%到30%的年轻人 已知的发病病例是由DNA错配修复缺陷引起的， 微卫星不稳定性MSI(H)的分子表型。我提议 评估那些微卫星稳定(MSS)的年轻发病肿瘤 同样的技术成功地为发现奠定了基础 至少三个主要抑癌基因(P53、DCC和APC)在结直肠癌中的表达。 将收集家族史、流行病学和临床数据，这 将对参与者队列进行纵向跟踪，以确定 结果。这些临床数据将与 从年轻人和老年人的肿瘤中确定的分子信息 发病病例，以便开发有用的算法用于患者管理和 为了检测可能影响预后的遗传事件，及早检测 以及预防和治疗策略。这些研究应该提供 有意义的科学数据，同时让我有广泛的曝光率 在几个重要的调查工具方面有丰富的经验。 为了进一步促进我的职业发展，我计划接受教学培训 与癌症预防研究相关的领域(包括负责的 进行研究)。在实现这些目标之后，我有信心 我将准备好继续我作为一名成功的独立人士的职业生涯 致力于预防和控制结直肠癌的研究人员。

DESCRIPTION (provided by applicant): The Cancer Prevention, Control and Population Sciences Career Development Award will provide an excellent opportunity for me to learn the skills necessary to conduct high-quality colerectal cancer prevention and control research. My proposed plan is targeted toward expanding our basic understanding of the molecular mechanisms underlying colerectal carcinogenesis, specifically within the young onset population. I plan to collect and characterize the tumors of 200 participants with young onset (less than 50 years of age) colerectal cancer (CRC) and 200 participants with older onset CRC. This particular segment of the CRC burden is not well understood with the exception that 15 to 30 percent of these young onset cases are known to be caused by defective DNA mismatch repair, having the molecular phenotype of microsatellite instability Msi(H). I propose to evaluate those young onset tumors that are microsatellite stable(MSS) with the same technique that successfully established the ground work for the discovery of at least three major tumor suppressor genes (p53, DCC, and APC) in CRC. Family history, epidemiological and clinical data will be collected and this cohort of participants will be followed longitudinally in order to determine outcome. These clinical data will be correlated with the results of the molecular information ascertained from the tumors of both the young and older onset cases, in order to develop useful algoritluns for patient management and to detect genetic events that may influence prognostication, early detection and prevention as well as treatment strategies. These studies should provide meaningful scientific data, while simultaneously affording me a broad exposure to and considerable experience with several important investigational tools. To further enhance my career development, I plan to obtain didactic training in areas relevant to cancer prevention research (including the responsible conduct of research). Following achievement of these goals, I am confident that I will be ready to continue my career as a successful independent investigator committed to colerectal cancer prevention and control.