Abstract IA09: Environmental contributors to childhood cancers
Authors: Metayer Catherine 
Published: June 2022

Abstract
Leukemia is the most common cancer in children living in industrialized countries. Its incidence has dramatically increased in the last decades in certain populations, such as Latino children in the United States, who have experienced a 35% increase in incidence rate in the past 40 years. Upward trends have also been observed for other cancers in children and adolescents with some variation by tumor site and geographic region. These observations overall point to the important role of the “environment” in a broad sense, whether acting alone or in concert with genetic factors, but can we say more? Despite decades of epidemiologic research on childhood leukemia, recent reports and publications often start with a general statement like “…we do not know what causes childhood leukemia…” or “…only 10% of childhood leukemia can be explained….” This session will challenge this perception by presenting the most salient results on children’s and parents’ exposures to carcinogens such as those contained in paints, solvents, pesticides, air pollution, and tobacco smoke and the risk of childhood leukemia. Since in utero nutrition is recognized as contributing to the alteration of gene expression and physical development in the fetus, we will also assess whether a healthy maternal diet during pregnancy and prenatal folate/vitamin supplementation reduce the risk of childhood leukemia. Advances in our understanding of actionable risk factors that increase or decrease the risk of childhood leukemia have been made at a faster pace than for most other childhood cancers, yet similar associations with chemical and nutritional factors have also been reported for certain solid tumors, suggesting a cumulative impact of these factors. A critical review of complementary study designs of childhood leukemia studies using various populations and sources of data, biomarkers of exposures, and molecular characterization of childhood leukemia subtypes will be presented to evaluate association vs. causation. Future research directions will be discussed on how to characterize cumulative exposures and how to further integrate genetic and mechanic studies to strengthen the evidence. This presentation will mainly draw from the work conducted in the past decades at the California-based Center for Integrative Research on Childhood Leukemia and the Environment (CIRCLE) and the Childhood Leukemia International Consortium (CLIC). CLIC assembled data for up to 40,000 leukemia cases and 350,000 controls from 38 case-control studies worldwide. This unprecedentedly large sample size has allowed to conduct pooled and meta-analyses for major leukemia subtypes and sociodemographic subgroups, providing the most robust findings to date. While the strength of international consortia resides in numbers and geographic variation that enable to examine the disease and exposure heterogeneity, other approaches are needed to provide mechanistic understanding of the observed associations, and to uncover factors that cannot be identified from “traditional” epidemiologic studies that use primarily self-reports or registry-based data. To that effect, the Children’s Center CIRCLE has developed innovative targeted and untargeted environmental and biomarker studies to characterize chemical exposures before and after birth. As evidence on the environmental risk factors for childhood leukemia and other cancer is accumulating, it is prudent to start prevention programs to reduce exposure to harmful environmental exposures and promote a healthy lifestyle, especially targeting vulnerable populations such as Latino families. Despite alarming statistics, federal funding for research that aims to identify causes of childhood cancers and promote prevention has been consistently dismal, putting more children at risk to be diagnosed with cancer and to suffer short- and long-term complications throughout their lives. It is therefore critical to invest in childhood cancer etiologic research and research translation that requires international and multidisciplinary collaborations.
References, resources, and funding: (1) Giddings BM, Whitehead TP, Metayer C, Miller MD. Childhood leukemia incidence in California: High and rising in the Hispanic population. Cancer 2016 Sep 15;122(18):2867-75; (2) Whitehead TP, Metayer C, Wiemels JL, Singer AW, Miller MD. Childhood leukemia and primary prevention. Curr Probl Pediatr Adolesc Health Care 2016 Oct;46(10):317-352; (3) CIRCLE website is available at www.circle.berkeley.edu; (4) CIRCLE is supported by grants from the NIEHS (#P50ES018172) and USEPA (#RD83615901)
Citation Format: Catherine Metayer. Environmental contributors to childhood cancers [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr IA09.