Genetic and environmental risk factors for childhood cancer

2015-06-07While epidemiologic studies of childhood cancer have been conducted for many decades, ionizing radiation is the only established environmental risk factor for childhood brain tumors and childhood leukemia. Other factors, such as pesticides, electromagnetic fields, smoking and immunologic challenge have been suggested, but not consistently demonstrated, as risk factors. Additionally, recent genome wide association studies (GWAS) of childhood leukemia have found variants in several genes that may increase risk of disease. However, it is likely that both genetic and environmental risk factors contribute to the incidence of childhood brain tumors and childhood leukemia. ❧ In my background chapter (chapter 1), I describe incidence, mortality, and 5-year survival, as well secular trends in incidence and mortality for both childhood brain tumors and childhood leukemias. I also review the various classifications of each disease, and suspected environmental and genetic risk factors, with an emphasis on the roles of parental smoking and exposure to pesticides prior to pregnancy, during pregnancy or in early childhood. ❧ In my second chapter, I describe my analysis of data from the West Coast Childhood Brain Tumor (WCCBT) study to evaluate gene-parental smoking interactions and risk of childhood brain tumors. The analysis focuses parental smoking during pregnancy and 9 selected candidate polymorphisms in 6 genes known to affect the activation or detoxification of polycyclic aromatic hydrocarbons, a suspected carcinogen found in tobacco smoke. The corresponding manuscript was published in PLoS One in October 2013. ❧ In chapter 3, I describe my analysis of trends in the incidence of childhood leukemia from 1973-2010 using complete Surveillance, Epidemiology and End Results (SEER) registry data. I evaluated secular trends by ethnicity (Hispanic vs. non-Hispanic) for incidence of all childhood leukemias, acute lymphocytic leukemia, and acute myeloid leukemia by demographic characteristics, including age, gender, race, and ethnicity. Chapter 3 includes a draft of the corresponding manuscript. ❧ In my fourth chapter, I describe my analysis of Hispanic participants enrolled in the California Childhood Leukemia Study (CCLS). I used two-step approaches to scan the genome for gene-parental smoking interactions associated with risk of childhood acute lymphocytic leukemia (ALL). We replicated results in the ESCALE study of childhood leukemia in France, and in the AUS-ALL study of childhood leukemia in Australia. A draft of the manuscript can be found in chapter 4. ❧ Chapter 5 includes a National Institute of Health (NIH) R21 grant that I submitted with Dr. Roberta McKean-Cowdin (chair, PI), Dr. W. James Gauderman (chair, Co-I), and Dr. Myles Cockburn (Co-I) in October 2013. The aims of this grant were 1) to evaluate the association between ambient pesticide exposure early in life and childhood ALL risk, using advanced exposure models and data from the California Childhood Leukemia Study, and 2) to evaluate the role of genetic susceptibility in the association between ambient pesticide exposure and ALL, using a genome-wide interaction scan (GWIS) analysis to scan the genome for susceptibility loci. The complete grant application can be found in chapter 5