Epidemiologic and germline genomic characterization of early-onset colorectal cancer among Hispanics

西班牙裔早发结直肠癌的流行病学和种系基因组特征

基本信息

批准号：
10557583
负责人：
Maria Gonzalez-Pons
金额：
$ 28.79万
依托单位：
UNIVERSITY OF PUERTO RICO MED SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-19 至 2028-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10557583
关键词：
Address Age Blood Cancer Burden Cancer Etiology Cancer health equity Caribbean region Centers for Disease Control and Prevention (U.S.)Cessation of life Clinical Colon Colorectal Cancer Complement Cuban Data Development Disparity Eating Epidemiologic Factors Epidemiological trend Epidemiology Ethnic Population Etiology Event Familial colorectal cancer Feces Foundations Freezing Future Generations Genes Genetic Genetic Variation Genomics Germ-Line Mutation Goals Hispanic Hispanic Populations Incidence Individual Knowledge Malignant Neoplasms Molecular Molecular Epidemiology Mucous Membrane National Cancer Program Normal tissue morphology Organoids Participant Pathogenicity Pathway interactions Patients Population Population Heterogeneity Positioning Attribute Predisposing Factor Prevention strategy Principal Investigator Process Prognosis Public Health Puerto Rican Puerto Rico Reporting Research Risk Factors SEER Program Sampling Subgroup Survival Rate Time Tumor Tissue Variant Woman biobank cancer health disparity cancer subtypes carcinogenicity cohort colon carcinogenesis colorectal cancer registry colorectal cancer risk early onset early onset colorectal cancer epidemiologic data ethnic health disparity exome sequencing genetic analysis genetic variant insight men mortality neoplasm registry novel programs prospective racial health disparity racial population recruit risk stratification skills sociodemographics survival disparity treatment strategy trend tumor

项目摘要

PROJECT SUMMARY/ABSTRACT Colorectal cancer (CRC) is the 1st and 2nd leading cause of cancer death in men and women in Puerto Rico and the in U.S., respectively. Although CRC incidence and mortality trends have been declining, overall, the incidence and mortality in individuals younger than 50 years (early-onset CRC) have been rising consistently, and the incidence of this CRC subtype is projected increase by more than 140% by 2030. Disparities in CRC incidence and survival have been well documented in racial/ethnic groups in the mainland U.S. However, aggregating heterogeneous populations, such as Hispanics, conceals the significant variability that exists within subgroups in terms of CRC incidence and mortality. CRC represents a malignancy with documented disparities when comparing Hispanics living in Puerto Rico (HPR) with racial/ethnic groups living in the mainland U.S., yet very little is known regarding early-onset epidemiological trends or the pre-disposing risk factors in this Hispanic subpopulation. Moreover, the etiology of early-onset CRC and how germline genetic variation may contribute to early-onset CRC health disparities remain poorly understood. With this in mind, the main goal of the proposed study is to: (Aim 1) characterize early-onset CRC sociodemographic and epidemiological trends in Puerto Rico for the first time; (Aim 2) identify germline genetic variants that predispose individuals to develop CRC before the age of 50; and (Aim 3) establish an early-onset CRC biospecimen (blood, normal mucosa and tumor tissue, and stool) and organoid biobank. Our central hypothesis is that we will observe disparities in early-onset CRC incidence and survival in HPR compared to other racial/ethnic groups in the mainland U.S. and that we will identify novel, unique variants associated with early-onset CRC in HPR. The successful completion of the proposed specific aims will put the principal investigator (PI) in a unique and advantageous position by allowing her to develop skills in molecular epidemiology, germline genetic analysis, and generation of CRC organoids, and in parallel will provide data that will be used as preliminary data for a future R01 submission examining novel risk-stratification, prevention, and/or treatment strategies in year 2. This study will significantly advance the field by providing insight into the factors contributing to the early-onset CRC burden among HPR, the genes and pathways that may contribute to colorectal carcinogenesis in young individuals (<50 years), and in establishing the first early-onset CRC biospecimen and organoid biobank in the Caribbean derived from HPR that will enable for future studies aimed at examining the early-onset CRC risk factors and pathogenic mechanisms, and will make comparisons to other racial/ethnic groups feasible. All of which, will provide the PI with the foundation to pursue new research avenues in her independent research program focused on elucidating the factors contributing to this age and racial/ethnic health disparity.

项目概要/摘要结直肠癌 (CRC) 是波多黎各男性和女性癌症死亡的第一和第二大原因和分别在美国。尽管结直肠癌的发病率和死亡率呈下降趋势，但总体而言， 50 岁以下人群（早发性 CRC）的发病率和死亡率持续上升，预计到 2030 年，该 CRC 亚型的发病率将增加 140% 以上。 CRC 的差异美国大陆的种族/族裔群体的发病率和生存率已得到充分记录。然而，聚合异质人群（例如西班牙裔）掩盖了显着的变异性 CRC 发病率和死亡率存在于亚组中。 CRC 代表一种恶性肿瘤将居住在波多黎各 (HPR) 的西班牙裔人与居住在波多黎各的种族/族裔群体进行比较时记录的差异在美国大陆，但人们对早发型流行病学趋势或易感人群知之甚少该西班牙裔亚群的危险因素。此外，早发性结直肠癌的病因学以及种系如何遗传变异可能导致早发性结直肠癌的健康差异仍然知之甚少。有了这个请注意，拟议研究的主要目标是：（目标 1）描述早发性 CRC 的社会人口特征和首次公布波多黎各的流行病学趋势；（目标 2）识别种系遗传变异个人在 50 岁之前容易患上结直肠癌；（目标 3）建立早发 CRC 生物样本（血液、正常粘膜和肿瘤组织以及粪便）和类器官生物库。我们的中央假设我们将观察到与 HPR 相比，早发性 CRC 发病率和生存率存在差异美国大陆的其他种族/族裔群体，我们将识别与 HPR 中的早发性 CRC。成功完成拟议的具体目标将使主要研究员（PI）通过让她发展分子技能，处于独特和有利的地位流行病学、种系遗传分析和 CRC 类器官的生成，同时将提供数据将用作未来 R01 提交的初步数据，审查新的风险分层、预防、和/或第二年的治疗策略。这项研究将通过提供以下方面的见解来显着推进该领域的发展： HPR 中导致早发性 CRC 负担的因素、可能的基因和途径有助于年轻个体（<50 岁）的结直肠癌发生，并建立第一个早发性结直肠癌加勒比地区源自 HPR 的 CRC 生物样本和类器官生物库将为未来的研究提供支持旨在检查早发CRC的危险因素和致病机制，并将进行比较其他种族/族裔群体也是可行的。所有这些，将为PI提供追求新的基础她的独立研究计划的研究途径侧重于阐明造成这一现象的因素年龄和种族/民族健康差异。