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

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.

Triple-hit explanation for the worse prognosis of pediatric acute lymphoblastic leukemia among Mexican and Hispanic children

“…Recent efforts by both local actors in LMICs and global health initiatives led by HIC institutions are aimed at lowering the survival gap by improving supporting care and applying intensified risk-based treatment protocols with appropriate patient education and treatment response assessment on follow-up, considering a comprehensive approach to society, leukemia biology, and treatment based of risk biologic factors ( 43 , 44 ).…”

Emotional and behavioral attitudes of Tunisian youth towards childhood leukemia: health education and primary prevention in perspective

“…For primary prevention and reduction of the prevalence of leukemia in Tunisia and other countries, it is relevant to target modifiable or avoidable risk factors. For example, paternal smoking, exposure to pesticides and nitrogen dioxide, are identified in the literature [ 53 ].…”

Parental occupational exposure to combustion products, metals, silica and asbestos and risk of childhood leukaemia: Findings from the Childhood Cancer and Leukaemia International Consortium (CLIC)

“…Although a growing body of research has targeted a broad range of potentially aetiologic factors, including perinatal factors, family and parental lifestyle factors, as well as environmental and occupational exposures ( Schüz and Erdmann, 2016 , Onyije et al, 2022 ), the aetiology of childhood leukaemia remains poorly understood and primary prevention measures are largely lacking. There have been numerous studies on parental occupational exposures for instance including pesticides and solvents (e.g., benzene) attracting scientific interest as potential predisposing factors for childhood leukaemia, with already around 50 studies published before the late 1990s ( Colt and Blair, 1998 ).…”