• Lead-oncoMap: Calibratable Multi-Organ Cancer Risk from Chronic Lead Exposure (LeadCaRisk)
  • Arezoo sadeghi,1,*
    1. Msc of Molecular Genetic Department of Genetics, Zanjan Branch, Islamic Azad University, Zanjan, Iran.


  • Introduction: Lead (Pb) remains a pervasive toxicant with no physiological role. Inorganic lead compounds are regarded as probably carcinogenic to humans, while chronic low-dose exposure continues in water, air and workplaces. Signals link cumulative lead to cancers of the meninges, kidney, lung and stomach, and to hippocampal injury with sustained neuroinflammation. Yet policy and clinical decisions still lack a transparent, quantitative tool that connects exposure, mechanisms and multi-organ cancer risk. We introduce Lead-oncoMap, an end-to-end framework that (i) models organ-specific hazard as a function of blood-lead, (ii) encodes mechanistic evidence (oxidative stress, impaired DNA repair, epigenetic dysregulation) as priors, (iii) yields a calibrated personal risk score (LeadCaRisk), and (iv) specifies a pragmatic path to validation and commercialization. The objective is to move from fragmented evidence to a reproducible, upgradeable pipeline that can guide screening and exposure-reduction in real-world settings.
  • Methods: We built site-specific, monotone log-linear dose–response functions relating blood-lead (2–50 µg/dL) to hazard for brain/meningioma, kidney, lung and stomach. Parameters were seeded from published cohort magnitudes (e.g., stronger meningioma signal in women) and constrained by mechanistic plausibility. A Bayesian updating scheme combines these priors with observed data; uncertainty is propagated to prediction intervals. We mapped outputs to a 0–100 LeadCaRisk index using piecewise-linear transforms that weight organ risks by age/sex and co-exposures (arsenic, cadmium, tobacco). To bridge bits-to-bench, we prespecified validation: (1) organoid-on-a-chip for hippocampal neurospheres, kidney proximal tubule, hepatocyte and bronchial epithelium, chronically exposed for 8–12 weeks to 2, 10, 30 µg/dL equivalents; readouts include ROS, γH2AX, RAD51 foci, comet assay, and targeted DNA-methylation. (2) A human pilot (n≈60; battery recyclers/plumbers vs matched controls) with repeated measures of blood and keratin lead, targeted methylation, and smartphone GPS diaries for time-varying exposure, analysed by hierarchical partial pooling to calibrate LeadCaRisk. Scenario modules quantify benefits of remediation (e.g., water filters, workplace controls). The software is containerized for auditability; parameters are versioned to enable rapid re-calibration as evidence accrues.
  • Results: Simulation produced dose-dependent increases across sites. Example hazard ratios (HR) at 10 µg/dL were ≈1.22 (brain/meningioma), 1.16 (kidney), 1.13 (lung) and 1.11 (stomach); at 30 µg/dL the respective HRs approximated 1.82, 1.57, 1.43 and 1.35. Internal sensitivity analysis showed LeadCaRisk decreases by ~8–15 points when blood-lead falls by 10 µg/dL, defining tangible impact thresholds for occupational medicine and municipal policy. Scenario testing indicated the steepest gradients for brain and kidney, prioritizing female workers for meningioma screening and high-exposure trades for kidney surveillance. A rule-set was derived: LeadCaRisk ≥70 triggers confirmatory testing and exposure audit; 50–69 prompts quarterly monitoring and remediation; <50 recommends annual follow-up. Ablation studies demonstrated that adding targeted methylation to blood/keratin lead improved simulated discrimination and tightened prediction intervals, supporting the companion-diagnostic concept. A reproducible figure and a compact table summarize the curves and thresholds to facilitate review.
  • Conclusion: Lead-oncoMap operationalizes decades of toxicology and epidemiology into an implementable, calibration-ready pipeline. Its novelty lies in unifying dose–response modelling, mechanistic priors, organoid/human calibration and actionable scoring for multi-organ cancer risk from chronic low-dose lead.The commercialization track is direct: (a) a CLIA-/ISO-ready kit measuring blood/keratin lead plus a small targeted methylation panel; (b) a SaaS dashboard for employers and municipalities that reports LeadCaRisk, trend alerts and projected risk reduction under specific remediation scenarios. Patentable components include the weighted index mapping, the minimal biomarker panel coupled to exposure diaries, and the calibration workflow that links organoid endpoints to human risk updates. By design, the pipeline is modular, data-hungry and falsifiable—inviting rapid external replication while delivering immediate utility for prevention, early detection and policy.
  • Keywords: Lead acetate; Cancer risk; Meningioma; Organoid-on-a-chip; Risk modelling