Background: Acute Lymphoblastic Leukemia (ALL) is the most common childhood malignancy, with a multifactorial etiology involving both genetic susceptibility and environmental exposures. Increasing evidence suggests that chronic exposure to pesticides, toxic metals, and disturbances in essential trace elements may contribute to carcinogenesis and partially explain the increased burden of ALL in agriculturally intensive regions.
Methods: We enrolled 80 pediatric ALL cases and 35 controls comprising healthy controls (n=22), solid tumor non-leukemic controls (n=3), familial controls (n=6), and geographically non-exposed controls (n=4). Plasma and whole blood samples were analyzed for 20 elemental profiles using inductively coupled plasma–mass spectrometry (ICP-MS). Simultaneously, 49 pesticides belonging to organochlorine, organophosphate, and pyrethroid classes were screened using triple quadrupole gas chromatography–mass spectrometry (GC-MS/MS). Appropriate statistical analyses were performed between groups.
Results: Copper levels were nearly two-fold higher in leukemia cases compared with controls (2143 vs. 1207 ppb, ****q<0.001), while zinc levels were significantly reduced (700 vs. 823 ppb, *q=0.026), resulting in a markedly elevated Cu/Zn ratio (****q<0.0001). Nickel levels were significantly increased (131 vs. 80 ppb, *q=0.012), whereas barium levels were decreased (307 vs. 400 ppb, *q=0.017), contributing to a significantly elevated Ni/Ba ratio (****q<0.0001). Aluminium demonstrated a pronounced rise, reaching toxic median concentrations (846 vs. 464 ppb, ***q=0.001). Elevated levels of strontium (*q=0.04), manganese (**q=0.002), and iron (3034 vs. 2259 ppb, *q=0.017) were also observed among cases, whereas selenium was significantly reduced (67 vs. 94.5 ppb, *q=0.04). Interestingly, lead concentrations were higher in controls (28 vs. 22 ppb, *q=0.017). Several banned pesticides were detected at concentrations 10–20-fold above permissible limits in both cases and controls. Permethrin levels were significantly elevated among leukemia cases (39 vs. 27 ppb, *q=0.04), whereas bioallethrin levels were higher in controls (*q=0.04). Notably, siblings of leukemia patients demonstrated detectable residues of high-risk IARC-classified carcinogenic pesticides including Group 1 (γ-lindane), Group 2A (aldrin, DDT), and Group 2B compounds (chlordane and chlorobenzene derivatives).
Conclusion: Pediatric ALL demonstrated marked elemental dysregulation and significant toxic exposure signatures. Elevated Cu/Zn and Ni/Ba ratios strongly differentiated leukemia cases from controls, suggesting their potential utility as exposure-associated biomarkers. Importantly, aluminium concentrations reached levels substantially above physiological ranges, highlighting a concerning toxic burden warranting further investigation. Detection of carcinogenic pesticide residues in siblings of leukemia patients additionally suggests the presence of persistent environmental exposure hotspots that may contribute to leukemogenesis through chronic metabolic stress, oxidative injury, and genomic instability.