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Understanding the Increased Risk of Childhood Acute Lymphoblastic Leukemia in Latinos

Award Number: R01CA262263
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2022
PERIOD OF PERFORMANCE END DATE: 04/30/2027

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Understanding the Increased Risk of Childhood Acute Lymphoblastic Leukemia in Latinos - 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $601,736 )
2025	2025	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Cancer Cause and Prevention Research	000	4	4/21/2025	NON-COMPETING CONTINUATION	$541,563
2025	2025	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Cancer Cause and Prevention Research	002	4	6/26/2025	NON-COMPETING CONTINUATION	$60,173
2025	2024	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Cancer Cause and Prevention Research	001	3	6/16/2025	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $601,736

Issue Date FY: 2024 ( Subtotal = $584,228 )
2024	2024	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90089	LOS ANGELES	USA	Cancer Cause and Prevention Research	000	3	5/9/2024	NON-COMPETING CONTINUATION	$510,146
2024	2024	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90089	LOS ANGELES	USA	Cancer Cause and Prevention Research	001	3	5/10/2024	SUPPLEMENT FOR EXPANSION	$74,082
														Subtotal = $584,228

Issue Date FY: 2023 ( Subtotal = $640,629 )
2023	2023	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST	LOS ANGELES	CA	90089	LOS ANGELES	USA	Cancer Cause and Prevention Research	000	2	5/4/2023	NON-COMPETING CONTINUATION	$640,629
														Subtotal = $640,629

Issue Date FY: 2022 ( Subtotal = $878,229 )
2022	2022	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Cancer Cause and Prevention Research	000	1	4/29/2022	NEW	$745,989
2022	2022	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Cancer Cause and Prevention Research	001	1	9/12/2022	SUPPLEMENT FOR EXPANSION	$132,240
														Subtotal = $878,229

Grand Total All Awards = $2,704,822

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Understanding the Increased Risk of Childhood Acute Lymphoblastic Leukemia in Latinos

Award Number: R01CA262263

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/01/2022

PERIOD OF PERFORMANCE END DATE: 04/30/2027

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