Environmental Risk Factors for Childhood Acute Lymphoblastic Leukemia: An Umbrella Review

SIMPLE SUMMARY: Leukemia is the most common type of cancer among children worldwide. The aim of this umbrella review was to provide an evidence-based summary of epidemiological studies on environmental risk factors and the risk of childhood acute lymphoblastic leukemia (ALL), by exposure window. Second aim was to assess the prevalence in the German population which determines the relevance on population level. Only low doses of ionizing radiation in early childhood and maternal exposure to general pesticides during pregnancy showed convincing evidence of an association with childhood ALL. Other risk factors vary in level of association. The results of this umbrella review should be interpreted with caution; as the evidence are mostly from case-control studies, where selection and recall bias are potential concerns. ABSTRACT: Leukemia is the most common type of cancer among children and adolescents worldwide. The aim of this umbrella review was (1) to provide a synthesis of the environmental risk factors for the onset of childhood acute lymphoblastic leukemia (ALL) by exposure window, (2) evaluate their strength of evidence and magnitude of risk, and as an example (3) estimate the prevalence in the German population, which determines the relevance at the population level. Relevant systematic reviews and pooled analyses were identified and retrieved through PubMed, Web of Science databases and lists of references. Only two risk factors (low doses of ionizing radiation in early childhood and general pesticide exposure during maternal preconception/pregnancy) were convincingly associated with childhood ALL. Other risk factors including extremely low frequency electromagnetic field (ELF-MF), living in proximity to nuclear facilities, petroleum, benzene, solvent, and domestic paint exposure during early childhood, all showed some level of evidence of association. Maternal consumption of coffee (high consumption/>2 cups/day) and cola (high consumption) during pregnancy, paternal smoking during the pregnancy of the index child, maternal intake of fertility treatment, high birth weight (≥4000 g) and caesarean delivery were also found to have some level of evidence of association. Maternal folic acid and vitamins intake, breastfeeding (≥6 months) and day-care attendance, were inversely associated with childhood ALL with some evidence. The results of this umbrella review should be interpreted with caution; as the evidence stems almost exclusively from case-control studies, where selection and recall bias are potential concerns, and whether the empirically observed association reflect causal relationships remains an open question. Hence, improved exposure assessment methods including accurate and reliable measurement, probing questions and better interview techniques are required to establish causative risk factors of childhood leukemia, which is needed for the ultimate goal of primary prevention.