Determining the risk factor profile and biology of colorectal cancer in Nigeria

确定尼日利亚结直肠癌的危险因素概况和生物学

• 批准号: 10398938
• 负责人: OLUSEGUN ISAAC ALATISE
• 金额: $ 35.56万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10398938
• 关键词: APC mutation; Address; Africa; Africa South of the Sahara; African; African American; African American population; African ancestry; Alcohol consumption; Atlas of Cancer Mortality in the United States; BRAF gene; Biology; Blood specimen; Cancer Biology; Cancer Burden; Cancer Control; Cancer Etiology; Cessation of life; Collaborations; Colorectal Cancer; Country; DNA Sequence Alteration; Data; Data Set; Detection; Diagnosis; Diet; Dietary History; Disease; Early Diagnosis; Enrollment; Environment; Environmental Exposure; Etiology; European; Evidence based intervention; Exposure to; Frequencies; Future; Genomics; Germ-Line Mutation; Health; Health Promotion and Education; Hereditary Nonpolyposis Colorectal Neoplasms; High Prevalence; High-Frequency Microsatellite Instability; Incidence; Income; Infectious Agent; Infrastructure; Inherited; Intervention; KRAS2 gene; Knowledge; Life; Life Style; Malignant Neoplasms; Maps; Medical History; Medical center; Memorial Sloan-Kettering Cancer Center; Microsatellite Instability; Molecular; Morbidity - disease rate; Multicenter Studies; Mutation; Nigeria; Nigerian; Obesity; Oncogenes; Oncology Group; Outcome; Overweight; Participant; Patients; Pattern; Persons; Population; Population Study; Prevention; Prognosis; Prospective cohort study; Questionnaires; Research; Resource-limited setting; Resources; Risk Factors; Savings; Smoking; Somatic Mutation; Subgroup; Testing; The Cancer Genome Atlas; Work; World Health Organization; base; biobank; black patient; cancer prevention; clinical database; clinically actionable; clinically significant; colon cancer patients; colorectal cancer prevention; colorectal cancer risk; cost effective; cost efficient; deep sequencing; early onset colorectal cancer; effective therapy; evidence base; genomic profiles; high risk; improved; insight; mortality; novel; population based; prospective; recruit; reproductive; screening; statistics; trend; tumor

ABSTRACT Colorectal cancer (CRC) incidence and mortality are rapidly rising in sub-Saharan Africa; CRC is now the 4th most common cancer in the World Health Organization-Africa region. This rising burden is mirrored in Nigeria, where more than half of patients die within one year of diagnosis. These statistics highlight the need for cost- effective, evidence-based prevention, screening, and treatment interventions in this limited-resource region. However, an understanding of risk factors and the genomic landscape of CRC in this population is needed to inform such efforts. Through the African Research Group for Oncology (ARGO), we have established infrastructure and local scientific partnerships for novel cancer studies in Nigeria. We have an existing clinical database and a biobank of tumor and matched normal blood specimens from 490 prospectively enrolled Nigerian CRC patients. Data suggest Nigerian CRCs may possess distinct etiology. Overweight/obesity, the most common CRC risk factor in the US, is ~3-fold less prevalent in Nigeria. Similarly, other established risk factors, such as smoking and alcohol use, are half as frequent in Nigeria, suggesting other common endemic factors (e.g., infectious agents, environment, or diet) may drive CRCs in Nigeria. Furthermore, our pilot sequencing data from 65 Nigerian tumors show clinically significant differences vs. US patients. For instance, tumors from Nigerian patients had ~2-fold fewer somatic APC mutations, more KRAS mutations, and ~3-fold higher prevalence of high microsatellite instability. We also found ~3-fold higher prevalence of hereditary Lynch syndrome in Nigerian patients. To extend these preliminary analyses and further define CRC etiology in Nigeria, we propose the first multi-center study of CRC risk factors and genomics in sub-Saharan Africa. We will use ARGO infrastructure to conduct a large, cost-efficient, opportunistic study to: 1) Identify risk factors for CRC in Nigeria. We will recruit 600 CRC cases matched to 1,200 cancer-free population-based controls. Participants will complete an existing questionnaire developed by our group for use in Nigeria to assess demographic, anthropometric, reproductive, lifestyle, dietary, and medical history. And 2) Characterize molecular features of CRC tumors in Nigeria. We will perform targeted deep sequencing of 468 established cancer genes in matched tumor/blood samples from a subset of 360 CRC cases enrolled in Aim 1. After combining with existing data from 65 patients (N=425), we will map cancer genes altered by somatic or germline mutations in Nigerian patients and compare our data to large existing US datasets. These aims will provide a better understanding of the risk factor and genomic features of CRC in a West African population – a first step towards improving prevention, screening, and treatment of the disease in this understudied population. In addition, the etiological insights gained through the work proposed have high potential applicability to understudied US populations with poor CRC outcomes, such as African American and early-onset CRC patients.

抽象的 结直肠癌 (CRC) 的发病率和死亡率在撒哈拉以南非洲地区迅速上升，现已成为第四大癌症； 尼日利亚是世界卫生组织非洲地区最常见的癌症之一。 超过一半的患者在诊断后一年内死亡，这些统计数据强调了成本的必要性。 在这个资源有限的地区采取有效、循证的预防、筛查和治疗干预措施。 然而，需要了解该人群中结直肠癌的风险因素和基因组图谱，以 通过非洲肿瘤学研究小组 (ARGO)，我们建立了此类工作。 我们在尼日利亚有一个现有的临床研究基础设施和当地科学合作伙伴关系。 数据库和肿瘤生物库以及来自 490 名预期登记的尼日利亚人的匹配正常血液样本 数据表明尼日利亚的结直肠癌可能具有不同的病因，其中最常见的是超重/肥胖。 在美国，常见的 CRC 风险因素在尼日利亚的发病率要低约 3 倍，其他既定风险因素也同样如此。 吸烟和饮酒等现象在尼日利亚的发生率只有尼日利亚的一半，这表明还有其他常见的地方性因素 （例如，传染源、环境或饮食）可能会推动尼日利亚的 CRC。 此外，我们的试点测序数据。 65 个尼日利亚肿瘤与美国患者的肿瘤显示出临床显着差异。 尼日利亚患者的体细胞 APC 突变少约 2 倍，KRAS 突变较多，高约 3 倍 我们还发现遗传性 Lynch 的患病率高出约 3 倍。 为了扩展这些初步分析并进一步确定尼日利亚的 CRC 病因， 我们提议在撒哈拉以南非洲地区开展第一个关于 CRC 风险因素和基因组学的多中心研究。 ARGO 基础设施可进行大型、具有成本效益的机会主义研究，以： 1) 确定 CRC 的风险因素 在尼日利亚，我们将招募 600 名 CRC 病例与 1,200 名无癌症人群对照参与者。 将完成我们小组开发的现有调查问卷，用于尼日利亚评估人口统计， 人体测量、生殖、生活方式、饮食和病史 2) 描述分子特征。 我们将对尼日利亚的 CRC 肿瘤进行匹配的 468 个已确定的癌症基因的靶向深度测序。 来自目标 1 中登记的 360 例 CRC 病例子集的肿瘤/血液样本。与来自 65 名患者 (N=425)，我们将绘制尼日利亚患者体细胞或种系突变改变的癌症基因图谱 并将我们的数据与美国现有的大型数据集进行比较，这些目标将有助于更好地了解风险。 西非人群中结直肠癌的因素和基因组特征——改善预防的第一步， 此外，还对这一被研究人群进行了疾病的筛查和治疗。 通过所提出的工作获得的结果对未充分研究的美国贫困人口具有很高的潜在适用性 CRC 结果，例如非裔美国人和早发性 CRC 患者。