Race, pathomolecular signature and colorectal cancer survival

种族、病理分子特征和结直肠癌生存

• 批准号: 8242520
• 负责人: Kristin Wallace
• 金额: $ 13.04万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-21 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8242520
• 关键词: Address; African American; Age; Age Factors; American; Award; BRAF gene; Cancer Center; Cancer Etiology; Cancer Patient; Cessation of life; Characteristics; Clinic; Clinical Research; Clinical Treatment; Colon Carcinoma; Colorectal Cancer; Colorectal Neoplasms; Comorbidity; Confounding Factors (Epidemiology); CpG Island Methylator Phenotype; Cross-Sectional Studies; Data; Diagnosis; Disease; Educational workshop; Enrollment; Epigenetic Process; Etiology; European; Excess Mortality; Goals; High Prevalence; Histologic; Incidence; Intervention; Joints; K-Series Research Career Programs; KRAS2 gene; Laboratories; Light; Location; Malignant Neoplasms; Medical; Mentors; Molecular; Molecular Epidemiology; Molecular Genetics; Morbidity - disease rate; Neoplasm Metastasis; Neoplasms; Outcome; Pathologic; Pathway interactions; Patients; Phase; Phenotype; Plant Roots; Population; Predisposition; Primary Neoplasm; Process; Public Health; Race; Registries; Reporting; Research; Research Personnel; Research Training; Role; Socioeconomic Status; Source; South Carolina; Specimen; Stage at Diagnosis; Staging; Survival Analysis; Survival Rate; Techniques; Testing; Training; Universities; base; cancer epidemiology; cancer prevention; career; cohort; experience; genetic epidemiology; improved; insight; medically underserved; mortality; novel; prognostic indicator; racial difference; response; responsible research conduct; sex; socioeconomics; symposium; treatment response; tumor

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.

描述（由申请人提供）：结直肠癌（CRC）是美国第三大常见恶性肿瘤，也是癌症死亡的第三大原因。与欧洲裔美国人 (EA) 相比，非洲裔美国人 (AA) 的 CRC 死亡率要高得多，这是由于其较高的发病率和较低的生存率所致。即使在控制了诊断阶段后，生存率的种族差异仍然存在。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。 K07 职业发展奖中提出的培训和研究计划将使我能够作为分子和遗传癌症流行病学的独立研究者过​​渡到学术生涯的下一阶段。培训计划由多项补充活动组成，包括：（1）教学培训（正式课程/研讨会），（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。该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存活率的作用。该研究计划分两项研究进行。在一项基于临床的研究 Aim one 中，我们将进行横断面分析，以全面准确地总结 CRC 中 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。具体来说，我们将估计 AA 与 EA 相比不良病理学（例如组织学类型、结肠位置、分级）和分子（例如 KRAS、BRAF、p53、CIMP、MSI）预后指标的比例。在目标 2 中，在目标 1 的基础上，我们将对一组 CRC 患者进行生存分析，以检验种族的共同影响 以及关于生存的病理和分子预后指标。具体来说，我们将测试以下假设：在调整混杂变量后，（a）与 EA 相比，年轻（<50 岁）的 AA 具有更高比例的不良病理分子预后指标和较差的生存率；（b）与 EA 相比，年长（50 岁）的 AA 具有相似的不良病理分子预后指标比例和相似的生存率。候选人致力于了解结直肠肿瘤种族差异的病因学，其指导团队的卓越和专业知识以及南卡罗来纳医科大学（指定的国家癌症中心）对减少癌症种族差异的强有力的机构承诺相结合，将帮助申请人成为一名独立研究员。当前提案的研究结果将最终在该奖项的第四年提交 R01。最终，我的目标是利用分子和遗传流行病学技术来减少南卡罗来纳州及其他地区 AA 和 EA 之间的发病率和生存率差异。