Race, pathomolecular signature and colorectal cancer survival

摘要 结直肠癌(CRC)是美国第三大常见恶性肿瘤，也是第三大致癌原因 死亡。与欧洲裔美国人(EA)相比，非裔美国人(AA)的CRC发病率要高得多 死亡率是较高发病率和较低存活率的函数。中国的种族差距 即使在诊断时控制了分期后，存活率仍然存在。造成这种情况的原因尚不清楚，但可能 解释包括肿瘤侵袭性的种族差异、社会经济变量和或 治疗相关因素。本次K07职业发展奖中提出的培训和研究计划将 使我能够过渡到我学术生涯的下一个阶段，成为一名分子领域的独立研究员 和遗传癌症流行病学。培训计划由几项补充活动组成，包括：(1) 教学培训(正规课程/讲习班)，(2)湿法实验室经验，(3)参加国家 会议和研讨会(4)指导临床研究和负责任地开展研究的培训。 研究计划的主要目标是调查种族、病理和分子预后的作用。 指标和CRC存活率。研究计划分两个阶段进行。在目标一，一项基于临床的研究， 我们将进行横断面分析，以全面准确地总结 AAS和EAS原发和转移肿瘤的病理、分子和病理分子特征 CRC。具体地说，我们将估计病理不良的比例(例如组织类型、结肠位置、 AAS与EAS的预后指标(如KRAS、BRAF、P53、CIMP、MSI)的比较。在……里面 目标2，在目标1的基础上，我们将对一组结直肠癌患者进行生存分析，以检查关节 种族、病理和分子预后指标对生存率的影响。具体地说，我们将测试 假设在对混杂变量进行调整后，(A)与EA相比，(A)更年轻(&50岁)的AA 将有更高比例的不良病理分子预后指标和更差的存活率，以及(B)年龄较大(E 50岁)AAs与EAs相比，具有相似比例的不良病理分子预后指标 以及类似的生存方式。候选人对了解种族病因的承诺相结合 结直肠肿瘤的差异，她的指导团队的卓越和专业知识以及 南卡罗来纳医科大学(指定为国家癌症中心)的机构承诺 减少癌症方面的种族差异将有助于申请者成为一名独立的研究人员。这项研究 本提案的最终结果将是在授标的第四年提交R01。最终， 我的目标是利用分子和遗传流行病学的技术来减少发病率的差异。 以及南卡罗来纳州和更远地区的AA和EA之间的生存。

ABSTRACT Colorectal cancer (CRC) is the 3rd most common malignancy in the US and the third leading cause of cancer death. Compared to European Americans (EAs), African Americans (AAs) have a substantially higher CRC mortality rate that is a function of both a higher incidence rate and lower survival rate. Racial disparities in survival persist even after controlling for stage at diagnosis. The reasons for this are not known, but possible explanations include racial differences in aggressiveness of the tumors, socioeconomic variables, and or treatment-related factors. The training and research plan proposed in this K07 career development award will enable me to transition to the next phase of my academic career as an independent investigator in molecular and genetic cancer epidemiology. The training plan consists of several complementary activities including: (1) didactic training (formal coursework/workshops), (2) wet-laboratory experience, (3) attendance at national conferences and seminars (4) mentored clinical research and training in the responsible conduct of research. The primary goal of the research plan is to investigate the role of race, pathologic and molecular prognostic indicators and CRC survival. The research plan is carried out in two studies. In Aim one, a clinic-based study, we will perform a cross-sectional analysis to provide a comprehensive and accurate summary of the pathologic, molecular, and pathomolecular features of primary and metastatic tumors in AAs and EAs with CRC. Specifically, we will estimate the proportion of poor pathologic (e.g. histologic type, colonic location, grade) and molecular (e.g. KRAS, BRAF, p53, CIMP, MSI) prognostic indicators in AAs compared to EAs. In Aim 2, building on Aim 1, we will perform a survival analysis in a cohort of CRC patients to examine the joint influence of race and pathologic and molecular prognostic indicators on survival. Specifically, we will test the hypotheses that after adjustment for confounding variables, (a) younger (<50 years old) AAs compared to EAs will have a higher proportion of poor pathomolecular prognostic indicators and worse survival and (b) older (e 50 years old) AAs compared to EAs will have similar proportions of poor pathomolecular prognostic indicators and similar survival. The combination of the candidate's commitment to understanding the etiology of the racial disparity in colorectal neoplasia, the excellence and expertise of her mentoring team and the strong institutional commitment of the Medical University of South Carolina (a designated National Cancer Center) to reduce the racial disparities in cancer will help the applicant become an independent researcher. The research findings from the present proposal will culminate in a submission of an R01 in year 4 of the award. Ultimately, my goal is draw on the techniques in molecular and genetic epidemiology to reduce the disparities in incidence and survival between AAs and EAs in South Carolina and beyond.