The proposed research builds on 13 years of experience with the Northern California Childhood Leukemia Study (NCCLS), a population-based case-control study which includes ~40% of Hispanics, a traditionally under-represented ethnic group. The proposed study will continue to use a multi- and transdisciplinary approach to comprehensively study environmental, molecular, genetic, biologic and epidemiologic factors of childhood leukemia, and to improve chemical exposure assessment. Approximately 1,000 childhood leukemia cases [830 acute lymphocytic leukemia (ALL) and 160 acute myelocytic leukemia (AML)] and ~1,230 matched controls have been enrolled with DNA for genotyping available in ~95% of subjects. The investigations proposed will examine how environmental and genetic risk factors for ALL interact, and explore the etiology of rare and understudied subtypes of childhood leukemia such as AML and other groups defined by molecular and epigenetic markers. To achieve adequate statistical power, we propose to enroll an additional ~660 childhood leukemia cases (~530 ALL;85 AML) and ~660 matched controls using an established comprehensive, rapid reporting network of pediatric oncologists in the 38 California study counties. The resulting total sample size of ~1,660 leukemia cases (1,360 ALL, 245 AML) and 1,890 matched controls will allow us to explore hypotheses related to pre- and post-natal residential exposures to pesticides, persistent organic pollutants, and sources of benzene exposure and increased risks of ALL and AML, and how these risks may vary by leukemia subtype and be modified by variants in metabolizing genes. We will also examine the influence of immune function on the risk of childhood ALL overall, B-cell ALL and common-ALL (c-ALL) subtypes, and how these associations are modified by genes involved in the regulation of immune function. We will conduct large scale genotyping of ~10,000 gene variants, and employ a number of recently developed approaches for analysis of complex multidimensional genetic and epidemiologic data.

Public Health Relevance

The multidisciplinary research team in the Northern California Childhood Leukemia Study (NCCLS) proposes to examine how environmental, immune, and genetic risk factors for childhood leukemia interact, and will explore the etiology of rare and understudied subtypes of leukemia. Detailed information on immunity and residential exposures to pesticides, persistent organic pollutants, and benzene will be available for approximately 1,660 leukemia cases and 1,890 matched controls, and biospecimens will be collected to conduct molecular and genetic susceptibility studies. The culturally diverse population of the NCCLS ensures that environmental and genetic exposures unique to Hispanics will be examined.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES009137-14
Application #
8309877
Study Section
Epidemiology of Cancer Study Section (EPIC)
Program Officer
Mcallister, Kimberly A
Project Start
1999-01-01
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
14
Fiscal Year
2012
Total Cost
$2,691,986
Indirect Cost
$984,081
Name
University of California Berkeley
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704
Whitehead, Todd P; Metayer, Catherine; Wiemels, Joseph L et al. (2016) Childhood Leukemia and Primary Prevention. Curr Probl Pediatr Adolesc Health Care 46:317-352
Hsu, Ling-I; Briggs, Farren; Shao, Xiaorong et al. (2016) Pathway Analysis of Genome-wide Association Study in Childhood Leukemia among Hispanics. Cancer Epidemiol Biomarkers Prev 25:815-22
Singer, Amanda W; Selvin, Steve; Block, Gladys et al. (2016) Maternal prenatal intake of one-carbon metabolism nutrients and risk of childhood leukemia. Cancer Causes Control 27:929-40
Metayer, Catherine; Scelo, Ghislaine; Kang, Alice Y et al. (2016) A task-based assessment of parental occupational exposure to organic solvents and other compounds and the risk of childhood leukemia in California. Environ Res 151:174-183
Marcotte, Erin L; Thomopoulos, Thomas P; Infante-Rivard, Claire et al. (2016) Caesarean delivery and risk of childhood leukaemia: a pooled analysis from the Childhood Leukemia International Consortium (CLIC). Lancet Haematol 3:e176-85
Whitehead, Todd P; Havel, Christopher; Metayer, Catherine et al. (2015) Tobacco alkaloids and tobacco-specific nitrosamines in dust from homes of smokeless tobacco users, active smokers, and nontobacco users. Chem Res Toxicol 28:1007-14
Walsh, Kyle M; de Smith, Adam J; Hansen, Helen M et al. (2015) A Heritable Missense Polymorphism in CDKN2A Confers Strong Risk of Childhood Acute Lymphoblastic Leukemia and Is Preferentially Selected during Clonal Evolution. Cancer Res 75:4884-94
Whitehead, Todd P; Crispo Smith, Sabrina; Park, June-Soo et al. (2015) Concentrations of Persistent Organic Pollutants in California Children's Whole Blood and Residential Dust. Environ Sci Technol 49:9331-40
Whitehead, Todd P; Crispo Smith, Sabrina; Park, June-Soo et al. (2015) Concentrations of persistent organic pollutants in California women's serum and residential dust. Environ Res 136:57-66
Singer, Amanda W; Weiser, Sheri D; McCoy, Sandra I (2015) Does Food Insecurity Undermine Adherence to Antiretroviral Therapy? A Systematic Review. AIDS Behav 19:1510-26

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