Understanding the Increased Risk of Childhood Acute Lymphoblastic Leukemia in Latinos
了解拉丁裔儿童儿童急性淋巴细胞白血病风险增加
基本信息
- 批准号:10615852
- 负责人:
- 金额:$ 64.06万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-05-01 至 2027-04-30
- 项目状态:未结题
- 来源:
- 关键词:AccountingAcute Lymphocytic LeukemiaAdmixtureAmericasAwarenessCaliforniaCesarean sectionCessation of lifeChildChildhoodChildhood Acute Lymphocytic LeukemiaChildhood LeukemiaCytomegalovirus InfectionsDataEnvironmental ExposureEnvironmental Risk FactorEpidemiologyEthnic OriginEtiologyEuropeanExhibitsFaceFutureGATA3 geneGene ExpressionGene FrequencyGeneral PopulationGeneticGenetic Predisposition to DiseaseGenetic RiskGenetic VariationGenomeGenomic SegmentGoalsGuatemalaHeritabilityHumanImmuneImmune responseImmunological ModelsIncidenceInfectionInferiorKnowledgeLatinoLatino PopulationLinkage DisequilibriumMalignant Childhood NeoplasmMalignant NeoplasmsMapsMeta-AnalysisModelingMorbidity - disease rateNative American AncestryNative AmericansNatural SelectionsNatureOutcomePediatric Oncology GroupPlayPopulationPreventionQuantitative Trait LociRecording of previous eventsReportingRiskRisk AssessmentRisk FactorsRoleSaint Jude Children&aposs Research HospitalSample SizeSurvivorsSusceptibility GeneTestingTexasTreesUnited StatesVariantVulnerable PopulationsWeightadmixture mappingcase controlcausal variantdisorder preventionepidemiology studyethnic disparitygenetic risk assessmentgenetic risk factorgenetic variantgenome wide association studygenome-widehigh riskimprovedin uteroinsightmodifiable risknovelpolygenic risk scorerisk mitigationrisk predictionrisk stratificationrisk varianttranscriptometranscriptomics
项目摘要
ABSTRACT
Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer and, despite advances in treatment, it
is still one of the leading causes of childhood death in the United States (US), and survivors face significant
lifelong treatment-related morbidities. Children of Latino ethnicity have the highest and fastest-increasing risk of
ALL in the US, and have lower survival than non-Latino whites; however, this ethnic disparity in incidence and
outcome is not fully understood. Elucidating the increased risk of ALL in Latino children may reveal novel insights
in the etiology of ALL in both Latino and non-Latino populations, and may highlight potential avenues for disease
prevention. We hypothesize that germline genetic variation plays an essential role in the increased ALL risk in
Latinos, that this risk is imparted via Native American ancestry, and that ALL risk alleles were selected in Native
Americans during European colonization of the Americas due to their beneficial effects on immune response to
new infections. We have assembled the largest ever case-control set of childhood ALL in Latinos, including over
5,400 cases and 27,000 controls from three independent studies in California, plus studies in Texas, Children’s
Oncology Group/St. Jude Children’s Research Hospital, and Guatemala. In our first aim, we will perform three
complementary approaches to discover novel common risk loci associated with childhood ALL: i) a genome-
wide association study (GWAS) meta-analysis, ii) admixture mapping to capitalize on the recently admixed
nature of Latino genomes, and iii) a transcriptome-wide association study to identify novel loci and to pinpoint
causal genes at known and novel risk regions. In our second aim, we will characterize the genetic variants in
terms of their association with local Native American ancestry and whether they exhibit evidence of directional
natural selection on the Native American branch of the human population tree. We will also characterize the
aggregate effects of common variants on childhood ALL risk and how this varies by ethnicity, via comprehensive
modeling of polygenic risk scores (PRS) for ALL in Latinos and in non-Latino whites. Finally, we will incorporate
our genetic findings into epidemiologic analyses, by accounting for common (PRS) genetic variants in ALL risk
models for immune-related risk factors in Latinos and non-Latino whites, including cesarean delivery and in utero
cytomegalovirus infection, both of which have shown stronger effects on ALL risk in Latinos and are potentially
modifiable risk factors. The results of this study will shed light on the etiology of childhood ALL in general and of
the increased risk of ALL in Latino children, which will help to alleviate this ethnic disparity and may inform future
approaches for childhood leukemia prevention.
抽象的
急性淋巴细胞白血病 (ALL) 是最常见的儿科癌症,尽管治疗方法取得了进步,但它
仍然是美国儿童死亡的主要原因之一,幸存者面临着巨大的压力
与终生治疗相关的疾病。拉丁裔儿童的患病风险最高且增长最快
全部生活在美国,且存活率低于非拉丁裔白人;然而,这种发病率和发病率的种族差异
结果尚未完全理解。阐明拉丁裔儿童患 ALL 的风险增加可能会揭示新的见解
拉丁裔和非拉丁裔人群中 ALL 的病因学,并可能突出疾病的潜在途径
预防。我们假设种系遗传变异在 ALL 风险增加中发挥重要作用
拉丁裔,这种风险是通过美洲原住民血统传递的,并且所有风险等位基因都是在原住民中选择的
在欧洲殖民美洲期间,美国人由于其对免疫反应的有益影响
新的感染。我们收集了有史以来最大的拉丁裔儿童 ALL 病例对照组,其中包括超过
来自加利福尼亚州三项独立研究的 5,400 例病例和 27,000 例对照,以及德克萨斯州、儿童医院的研究
肿瘤学组/圣。裘德儿童研究医院和危地马拉。在我们的第一个目标中,我们将执行三个
发现与儿童 ALL 相关的新常见风险位点的补充方法:i) 基因组-
广泛关联研究(GWAS)荟萃分析,ii)混合映射以利用最近混合的
拉丁裔基因组的性质,以及 iii) 一项全转录组关联研究,以确定新的基因座并查明
已知和新风险区域的致病基因。在我们的第二个目标中,我们将描述遗传变异的特征
他们与当地美洲原住民血统的联系以及他们是否表现出方向性的证据
人类种群树的美洲原住民分支上的自然选择。我们还将描述
通过综合分析,常见变异对儿童 ALL 风险的总体影响以及该风险如何因种族而异
拉丁裔和非拉丁裔白人的 ALL 多基因风险评分 (PRS) 模型。最后,我们将合并
通过考虑 ALL 风险中的常见 (PRS) 遗传变异,将我们的遗传发现纳入流行病学分析
拉丁裔和非拉丁裔白人免疫相关危险因素模型,包括剖腹产和子宫内分娩
巨细胞病毒感染,这两种病毒感染对拉丁美洲人的 ALL 风险都有更强的影响,并且有可能
可改变的风险因素。这项研究的结果将揭示儿童 ALL 的一般病因和
拉丁裔儿童患 ALL 的风险增加,这将有助于缓解这种种族差异,并可能为未来提供信息
儿童白血病预防方法。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Adam De Smith其他文献
Adam De Smith的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Adam De Smith', 18)}}的其他基金
Understanding the Increased Risk of Childhood Acute Lymphoblastic Leukemia in Latinos
了解拉丁裔儿童儿童急性淋巴细胞白血病风险增加
- 批准号:
10440966 - 财政年份:2022
- 资助金额:
$ 64.06万 - 项目类别:
Genetic determinants of lymphocyte traits and risk of acute lymphoblastic leukemia in children with Down syndrome
唐氏综合症儿童淋巴细胞特征和急性淋巴细胞白血病风险的遗传决定因素
- 批准号:
10700064 - 财政年份:2022
- 资助金额:
$ 64.06万 - 项目类别:
Understanding the Increased Risk of Childhood Acute Lymphoblastic Leukemia in Latinos
了解拉丁裔儿童儿童急性淋巴细胞白血病风险增加
- 批准号:
10629825 - 财政年份:2022
- 资助金额:
$ 64.06万 - 项目类别:
Backtracking Leukemia-Typical Somatic Alterations in Cord Blood at Single-cell Resolution
以单细胞分辨率回溯脐带血中白血病典型体细胞改变
- 批准号:
10459501 - 财政年份:2021
- 资助金额:
$ 64.06万 - 项目类别:
Backtracking Leukemia-Typical Somatic Alterations in Cord Blood at Single-cell Resolution
以单细胞分辨率回溯脐带血中白血病典型体细胞改变
- 批准号:
10693149 - 财政年份:2021
- 资助金额:
$ 64.06万 - 项目类别:
Backtracking Leukemia-Typical Somatic Alterations in Cord Blood at Single-cell Resolution
以单细胞分辨率回溯脐带血中白血病典型体细胞改变
- 批准号:
10274321 - 财政年份:2021
- 资助金额:
$ 64.06万 - 项目类别:
Exploring the shared genetic architecture of white blood cell variation and childhood acute lymphoblastic leukemia
探索白细胞变异和儿童急性淋巴细胞白血病的共同遗传结构
- 批准号:
10063853 - 财政年份:2019
- 资助金额:
$ 64.06万 - 项目类别:
相似海外基金
Understanding of the onset and recurrence pattern of intractable acute lymphocytic leukemia based on clone analysis
基于克隆分析了解难治性急性淋巴细胞白血病的发病和复发模式
- 批准号:
20K08723 - 财政年份:2020
- 资助金额:
$ 64.06万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Novel Inhibitors of Multi-Drug-Resistant Mutants of BCR-ABL for the Treatment of Chronic Myelogenous Leukemia (CML) and Ph Positive Acute Lymphocytic Leukemia (ALL).
BCR-ABL 多重耐药突变体的新型抑制剂,用于治疗慢性粒细胞白血病 (CML) 和 Ph 阳性急性淋巴细胞白血病 (ALL)。
- 批准号:
9047400 - 财政年份:2015
- 资助金额:
$ 64.06万 - 项目类别:
The Role of Genetic Variants in Sensitivity to Methotrexate in Acute Lymphocytic Leukemia Survivors
遗传变异在急性淋巴细胞白血病幸存者对甲氨蝶呤敏感性中的作用
- 批准号:
319114 - 财政年份:2014
- 资助金额:
$ 64.06万 - 项目类别:
Fellowship Programs
Targeting the Bone Marrow Microenvironment In Acute Lymphocytic Leukemia
针对急性淋巴细胞白血病的骨髓微环境
- 批准号:
8595788 - 财政年份:2013
- 资助金额:
$ 64.06万 - 项目类别:
Targeting hypoxic microenvironment in Acute Lymphocytic Leukemia
针对急性淋巴细胞白血病的缺氧微环境
- 批准号:
8023518 - 财政年份:2011
- 资助金额:
$ 64.06万 - 项目类别:
Targeting hypoxic microenvironment in Acute Lymphocytic Leukemia
针对急性淋巴细胞白血病的缺氧微环境
- 批准号:
8404025 - 财政年份:2011
- 资助金额:
$ 64.06万 - 项目类别:
Targeting hypoxic microenvironment in Acute Lymphocytic Leukemia
针对急性淋巴细胞白血病的缺氧微环境
- 批准号:
8220724 - 财政年份:2011
- 资助金额:
$ 64.06万 - 项目类别:
Targeting hypoxic microenvironment in Acute Lymphocytic Leukemia
针对急性淋巴细胞白血病的缺氧微环境
- 批准号:
8599754 - 财政年份:2011
- 资助金额:
$ 64.06万 - 项目类别:
INSULIN RESISTANCE IN CHILDREN WITH ACUTE LYMPHOCYTIC LEUKEMIA UNDERGOING INDUCT
正在接受治疗的急性淋巴细胞白血病儿童的胰岛素抵抗
- 批准号:
8356701 - 财政年份:2010
- 资助金额:
$ 64.06万 - 项目类别:
INSULIN RESISTANCE IN CHILDREN WITH ACUTE LYMPHOCYTIC LEUKEMIA UNDERGOING INDUCT
正在接受治疗的急性淋巴细胞白血病儿童的胰岛素抵抗
- 批准号:
8166720 - 财政年份:2009
- 资助金额:
$ 64.06万 - 项目类别:














{{item.name}}会员




