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
- 批准号:10629701
- 负责人:
- 金额:$ 19.56万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 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:
- 关键词:AfricaAfrica South of the SaharaAfricanAfrican ancestryBackBiological Specimen BanksBiologyBloodClinicalColorectal CancerDataDevelopmentDiagnosisDiseaseDisease PathwayEpidemiologic FactorsEuropeanFundingFutureGenesGeneticGenomeGenomicsHereditary Nonpolyposis Colorectal NeoplasmsHigh PrevalenceIncidenceIndividualInfrastructureInheritedInterventionLifeMalignant NeoplasmsMicrosatellite InstabilityMulticenter StudiesNigeriaNigerianOncogenesOncology GroupOutcomeParentsPatientsPhenotypePopulationPopulation GeneticsPreventionResearchResource-limited settingResourcesRisk FactorsSamplingSavingsSignal TransductionSourceUnited States National Institutes of HealthWorld Health Organizationcancer geneticscolon cancer patientscolorectal cancer riskcost effectiveepidemiology studyevidence basegene discoverygenome sequencinggenomic datainterestmortalitynovelparent projectpolygenic risk scoreresponserisk variantscreeningtumorwhole genome
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:本申请是应特别利益通知(NOSI)的要求提交的
不是-CA-22-056。我们要求对250例表型良好的结直肠癌进行种系全基因组测序
在尼日利亚,有250例结直肠癌病例和250例匹配的非癌症对照。这些生殖系数据将提高
我们的NCI资助的项目是尼日利亚第一个关于结直肠癌风险因素和肿瘤遗传学的多中心研究。我们的
父母研究的动机是该地区结直肠癌发病率和死亡率的迅速上升;结直肠癌现在是第四位
世界卫生组织非洲地区最常见的癌症。这种不断增加的负担在尼日利亚也有反映,
50%的患者在确诊后一年内死亡。这突显了具有成本效益和循证的必要性
在这个资源有限的地区进行预防、筛查和治疗干预。然而,严重的匮乏
非洲人口中数据的多样性阻碍了我们开展这种努力的能力。非洲研究小组
肿瘤学(ARGO)已经为尼日利亚的癌症研究建立了基础设施和当地科学伙伴关系。
我们已经保存了样本,并成功地对ARGO样本进行了测序。北京地区505个癌症基因的测序
来自尼日利亚的结直肠癌患者的肿瘤/配对血液鉴定出显著的体细胞和生殖系差异。
我们的病人。尼日利亚患者肿瘤中高微卫星不稳定性的患病率高3倍
在其他差异中,遗传性林奇综合征的患病率高出约3倍。只有505个基因的数据
表明尼日利亚的CRC具有独特的生物学特性--加强了非洲对扩展基因组数据的需求
以确认这些发现,并确定可能的特定于人群的CRC基因。支持大型NCI
财团已经非常成功,发现了大约100个CRC信号,并指出了新的疾病
小路。然而,严重的欧洲偏见限制了它们的普遍性,并限制了对非洲血统的更大包容
个人在探索方面的努力是至关重要的。扩展的1000基因组计划已经对整个
893名非洲血统个人(包括327名尼日利亚人)的基因组;然而,这些数据不是设计出来的
检查癌症结果、流行病学因素或与生殖系改变相一致的躯体改变。
我们将利用我们正在进行的父项目,通过在
在尼日利亚,约有250例结直肠癌病例和约250例匹配的非癌症对照组。我们将最大化我们的价值
通过将全基因组序列数据与亲本个体水平数据相结合来研究未充分研究的群体
项目,包括结果,505个癌症基因的体细胞和生殖系变化,临床因素,以及
流行病学因素。当这些数据与NIH支持的其他数据结合时,将成为强大的资源
倡议,并可帮助加强基因发现研究的多样性,作为非洲血统控制的来源,
或者作为西非人的额外基因组参考。我们还将评估多基因
从尼日利亚具有结直肠癌风险的已知风险等位基因构建的风险分数,以告知是否在很大程度上发现了基因座
NIH的费用可以应用于西非人,而大规模的基因发现工作仍有待进行。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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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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