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: 10630075
• 负责人: OLUSEGUN ISAAC ALATISE
• 金额: $ 34.97万
• 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 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10630075
• 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; Disparity; Early Diagnosis; Enrollment; Environment; Environmental Exposure; Etiology; European; European ancestry; 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; Smoking; Somatic Mutation; Subgroup; Testing; The Cancer Genome Atlas; Work; World Health Organization; 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 撒哈拉以南非洲的结直肠癌（CRC）发病率和死亡率迅速上升； CRC现在是第四名 世界卫生组织 - 非洲地区最常见的癌症。这种上升的烧伤在尼日利亚镜像， 在诊断后的一年内，超过一半的患者死亡。这些统计数据凸显了需要成本的 有效的，基于证据的预防，筛查和治疗干预措施。 但是，需要了解该人群中CRC的危险因素和基因组景观 告知这样的努力。通过非洲肿瘤学研究小组（ARGO），我们建立了 尼日利亚新型癌症研究的基础设施和本地科学伙伴关系。我们有现有的临床 数据库和肿瘤的生物库，并匹配490名尼日利亚人的490个正常血样 CRC患者。数据表明尼日利亚CRC可能具有不同的病因。超重/肥胖，最多 在美国，常见的CRC风险因素在尼日利亚的普遍性降低了约3倍。同样，其他已建立的风险因素， 在尼日利亚，吸烟和饮酒等频率频繁，这表明其他常见的内在因素 （例如，传染剂，环境或饮食）可能在尼日利亚驱动CRC。此外，我们的试点测序数据 与美国患者相比，从65种尼日利亚肿瘤显示出临床显着差异。例如，来自 尼日利亚患者的体细胞APC突变减少了约2倍，KRAS突变更多，高约3倍 高卫星不稳定性的患病率。我们还发现遗传林奇的患病率高约3倍 尼日利亚患者的综合征。为了扩展这些初步分析并进一步定义了尼日利亚的CRC病因， 我们建议在撒哈拉以南非洲的CRC风险因素和基因组学首次多中心研究。我们将使用 Argo基础设施进行大型，具有成本效益的机会性研究至：1）确定CRC的风险因素 在尼日利亚。我们将招募600例CRC病例，匹配1,200个基于人群的对照。参与者 将完成我们小组在尼日利亚使用的现有调查表，以评估人口统计学， 人体测量学，生殖，生活方式，饮食和病史。 2）表征分子特征 尼日利亚的CRC肿瘤。我们将对匹配的468个已建立的癌症基因进行有针对性的深度测序 来自AIM 1的360例CRC病例的子集的肿瘤/血液样本。与现有数据结合后 65例患者（n = 425），我们将绘制尼日利亚患者的体细胞或种系突变改变的癌症基因 并将我们的数据与大型现有的美国数据集进行比较。这些目标将更好地了解风险 CRC在西非人口中的因素和基因组特征 - 改善预防的第一步， 筛查和治疗该疾病的人群。此外，病因见解 通过拟议的工作获得具有很高的潜在适用性，可以理解贫困的美国人群 CRC结果，例如非裔美国人和早期发作的CRC患者。

项目成果

Validating a semi-quantitative food frequency questionnaire to assess regional diet in a study of cancer in South West Nigeria.

• DOI: 10.1007/s10552-023-01684-0
• 发表时间: 2023-06
• 期刊: CANCER CAUSES & CONTROL
• 影响因子: 2.3
• 作者: Samson, Marguerite L.;Peeri, Noah C.;Alatise, Olusegun Isaac;O'Connell, Kelli;Sharma, Avinash;Ogunleye, Samson Gbenga;Aderounmu, Adewale A.;Olasehinde, Olalekan;Ogundokun, Akinjide Olurotimi;Ikujenlola, Abiodun Victor;Fatusi, Adesegun;Kingham, T. Peter;Du, Mengmeng
• 通讯作者: Du, Mengmeng

Healthcare utilisation, cancer screening and potential barriers to accessing cancer care in rural South West Nigeria: a cross-sectional study.

• DOI: 10.1136/bmjopen-2020-040352
• 发表时间: 2021-07-26
• 期刊: BMJ open
• 影响因子: 2.9
• 作者: Sharma A;Alatise OI;O'Connell K;Ogunleye SG;Aderounmu AA;Samson ML;Wuraola F;Olasehinde O;Kingham TP;Du M
• 通讯作者: Du M