Race, pathomolecular signature and colorectal cancer survival

描述（由申请人提供）：结直肠癌（CRC）是美国第三大最常见的恶性肿瘤，也是癌症死亡的第三大原因。与欧洲裔美国人（EAs）相比，非洲裔美国人（AAs）的CRC死亡率要高得多，这是高发病率和低存活率的共同作用。即使在控制了诊断阶段之后，种族间的生存差异仍然存在。其原因尚不清楚，但可能的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，成为一名独立的癌症分子和遗传流行病学研究者。培训计划包括几个补充活动，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)指导临床研究和负责任的研究行为培训。研究计划的主要目标是调查种族、病理和分子预后指标与结直肠癌生存的作用。本研究计划分两部分进行。在Aim 1，一项基于临床的研究中，我们将进行横断面分析，以全面准确地总结aa和ea合并CRC的原发性和转移性肿瘤的病理、分子和病理分子特征。具体而言，我们将评估与EAs相比，AAs中不良病理（如组织学类型、结肠位置、分级）和分子（如KRAS、BRAF、p53、CIMP、MSI）预后指标的比例。在Aim 2中，在Aim 1的基础上，我们将在一组CRC患者中进行生存分析，以检查种族的共同影响

DESCRIPTION (provided by applicant): 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.