Collecting whole genome sequence data to enhance the value of the first multi-center study of colorectal cancer risk factors and biology in Nigeria

收集全基因组序列数据,以提高尼日利亚首个结直肠癌危险因素和生物学多中心研究的价值

基本信息

项目摘要

ABSTRACT: This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT-CA-22-056. We request germline whole genome sequencing in 250 well-phenotyped colorectal cancer (CRC) cases and 250 matched cancer-free controls in Nigeria. These germline data will enhance the value of our NCI-funded project, the first multi-center study of risk factors and tumor genetics for CRC in Nigeria. Our parent study is motivated by the rapidly rising incidence and mortality of CRC in this region; CRC is now the 4th most common cancer in the World Health Organization-Africa region. This rising burden is mirrored in Nigeria, where >50% of patients die within 1 year of diagnosis. This highlights the need for cost-effective, evidence-based prevention, screening, and treatment interventions in this limited-resource region. However, the severe dearth of data in African populations hinders our ability to develop such efforts. The African Research Group for Oncology (ARGO) has established infrastructure and local scientific partnerships for cancer studies in Nigeria. We have banked specimens and successfully sequenced ARGO samples. Sequencing of 505 cancer genes in tumors/matched blood from 64 Nigerian CRC patients identified compelling somatic and germline differences vs. US patients. Nigerian patients had ~3-fold higher prevalence of high microsatellite instability in their tumors and ~3-fold higher prevalence of hereditary Lynch syndrome, among other differences. Data in only 505 genes suggest CRC in Nigeria possesses unique biology—reinforcing the need for expanded genomic data in African populations to confirm these findings and identify possible population-specific CRC genes. Large NCI-supported consortia have been remarkably successful, uncovering ~100 CRC signals and pointing to novel disease pathways. However, heavy European bias limits their generalizability, and greater inclusion of African ancestry individuals in discovery efforts is essential. The expanded 1000 Genomes Project has sequenced the entire genomes of 893 African ancestry individuals (including 327 Nigerians); however, these data were not designed to examine cancer outcomes, epidemiologic factors, or somatic alterations in concert with germline alterations. We will use our ongoing parent project to augment these efforts by creating a comprehensive resource in ~250 CRC cases and ~250 matched cancer-free controls in Nigeria. We will maximize the value of our understudied population by combining whole genome sequence data with individual-level data in our parent project, including outcomes, somatic and germline alterations in 505 cancer genes, clinical factors, and epidemiologic factors. These data will serve as a powerful resource when combined with other NIH-backed initiatives and can help bolster diversity in gene discovery studies, serve as a source of African ancestry controls, or act as an additional genomic reference for West Africans. We will also evaluate the utility of a polygenic risk score constructed from known risk alleles with CRC risk in Nigeria to inform if loci uncovered at great NIH expense can be applied in West Africans while large-scale gene discovery efforts remain to be conducted.
摘要:本申请是针对已确定的特殊利益通知(NOSI)提交的

项目成果

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OLUSEGUN ISAAC ALATISE其他文献

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{{ truncateString('OLUSEGUN ISAAC ALATISE', 18)}}的其他基金

Expanding cancer research capacity in Nigeria with team science
通过团队科学扩大尼日利亚的癌症研究能力
  • 批准号:
    10438142
  • 财政年份:
    2022
  • 资助金额:
    $ 19.56万
  • 项目类别:
Expanding cancer research capacity in Nigeria with team science
通过团队科学扩大尼日利亚的癌症研究能力
  • 批准号:
    10588180
  • 财政年份:
    2022
  • 资助金额:
    $ 19.56万
  • 项目类别:
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
  • 财政年份:
    2020
  • 资助金额:
    $ 19.56万
  • 项目类别:
Mentoring a Nigerian junior investigator with a mixed-methods analysis of barriers to colorectal cancer presentation in Nigeria
指导一名尼日利亚初级研究员对尼日利亚结直肠癌表现的障碍进行混合方法分析
  • 批准号:
    10623852
  • 财政年份:
    2020
  • 资助金额:
    $ 19.56万
  • 项目类别:
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
  • 财政年份:
    2020
  • 资助金额:
    $ 19.56万
  • 项目类别:
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:
    10227199
  • 财政年份:
    2020
  • 资助金额:
    $ 19.56万
  • 项目类别:
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:
    10053881
  • 财政年份:
    2020
  • 资助金额:
    $ 19.56万
  • 项目类别:
Point of care, real-time urine metabolomics test to diagnose colorectal cancers and polyps in low- and middle-income countries
护理点实时尿液代谢组学测试可诊断低收入和中等收入国家的结直肠癌和息肉
  • 批准号:
    9221852
  • 财政年份:
    2017
  • 资助金额:
    $ 19.56万
  • 项目类别:
Point of care, real-time urine metabolomics test to diagnose colorectal cancers and polyps in low- and middle-income countries
护理点实时尿液代谢组学测试可诊断低收入和中等收入国家的结直肠癌和息肉
  • 批准号:
    10173098
  • 财政年份:
    2017
  • 资助金额:
    $ 19.56万
  • 项目类别:
Point of care, real-time urine metabolomics test to diagnose colorectal cancers and polyps in low- and middle-income countries
护理点实时尿液代谢组学测试可诊断低收入和中等收入国家的结直肠癌和息肉
  • 批准号:
    10378649
  • 财政年份:
    2017
  • 资助金额:
    $ 19.56万
  • 项目类别:

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ESE:合作研究:撒哈拉以南非洲的气候变化和变异性以及武装冲突
  • 批准号:
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Network Dynamics, Sexual Behaviour, and HIV Among University Students in Africa South of the Sahara
撒哈拉以南非洲大学生的网络动态、性行为和艾滋病毒
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Synopsis of Ichneumoniae of Africa, South of the Sahara
撒哈拉以南非洲的姬蜂病简介
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    66B2956
  • 财政年份:
    1966
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    $ 19.56万
  • 项目类别:
To Attend Synopsis of Ichneumoninae of Africa, South of the Sahara
参加撒哈拉以南非洲的姬蜂亚科概要
  • 批准号:
    65B2956
  • 财政年份:
    1965
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