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，也是第三大癌症原因 死亡与欧洲裔美国人（EA）相比，非洲裔美国人（AA）的CRC显著更高 死亡率是较高发病率和较低存活率的函数。中的种族差异 即使在诊断时控制了分期后，存活率仍然存在。其原因尚不清楚，但有可能 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。K 07职业发展奖中提出的培训和研究计划将 使我能够过渡到我的学术生涯的下一个阶段，作为一个独立的分子研究者， 和遗传癌症流行病学。培训计划包括几项补充活动，包括：（1） 教学培训（正式课程/讲习班），（2）湿实验室经验，（3）参加国家 会议和研讨会（4次）指导临床研究和负责任地开展研究的培训。 该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中， 我们将进行横断面分析，以提供全面和准确的总结， AA和EA中原发性和转移性肿瘤的病理、分子和病理分子特征， 《儿童权利公约》。具体而言，我们将估计不良病理（例如组织学类型，结肠位置， 分级）和分子（如KRAS、BRAF、p53、CIMP、MSI）预后指标。在 目标2，在目标1的基础上，我们将在一组CRC患者中进行生存分析，以检查关节 种族、病理和分子预后指标对生存的影响。具体来说，我们将测试 假设在调整混杂变量后，（a）与EA相比，年轻（<50岁）的AA 将有较高比例的不良病理分子预后指标和较差的生存率和（B）年龄较大（e 50岁）与EA相比，AA具有相似比例的不良病理分子预后指标 类似的生存。候选人致力于了解种族歧视的病因， 结直肠肿瘤的差异，她的指导团队的卓越和专业知识，以及强大的 南卡罗来纳州医科大学（指定的国家癌症中心）的机构承诺， 减少癌症的种族差异将有助于申请人成为独立的研究人员。研究 本提案的调查结果将最终导致在授予的第4年提交R 01。最后， 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其他地区的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.