A cohort mortality study was conducted of 123,401 industrial radiographers in the United States to estimate risks following protracted radiation exposures. The cohort was constructed from the Nuclear Regulatory Commission Radiation Exposure Information Reporting System and the Landauer, Inc. dosimetry databases. Workers were monitored between 1939 and 2011 and were exposed mainly to external gamma radiation from 192Ir and 60Co. Causes of death were obtained from the National Death Index and state mortality files with follow-up through 2019. The mean duration of follow-up was 27.7 years. Nearly 19% of workers were monitored for more than 10 years. There were 30,617 (24.8%) who worked at shipyards and 5,071 (4.1%) at nuclear power plants with the potential for asbestos exposure. The mean radiation dose to the red bone marrow (RBM) was 15.2 mGy (maximum 1.24 Gy; percent >100 mGy was 3.6%), 17.2 mGy to lung, 18.1 mGy to colon, 11.9 mGy to brain, and 18.1 mGy to heart. Overall, 30,537 deaths occurred; the Standardized Mortality Ratio and 95% confidence interval for all-cause mortality was 0.92 (0.91, 0.93); for all solid cancers 1.01 (0.99, 1.03; n = 7,734); for ischemic heart disease (IHD) 0.83 (0.81; 0.85; n = 5,820); for cerebrovascular disease (CeVD) 0.88 (0.83, 0.93; n = 1,257); for mesothelioma 6.08 (5.35, 6.89; n = 248); and for asbestosis 13.4 (11.2, 15.9; n = 134). The linear excess relative risk (ERR) per 100 mGy (95% CI) for leukemia (excluding CLL) was 0.45 (0.05, 0.85) and for non-Hodgkin lymphoma (NHL) was 0.33 (0.04; 0.62). For all solid cancers it was 0.06 (0.02, 0.10); lung cancer 0.11 (0.04, 0.19); all solid cancers excluding lung cancer and mesothelioma 0.02 (-0.03, 0.07); Parkinson's disease 0.24 (-0.13, 0.61); IHD -0.03 (-0.06, 0.01); and CeVD 0.05 (-0.08, 0.17). The ERR per 100 mGy for chronic obstructive pulmonary disease (COPD) was 0.19 (0.08, 0.30) and was similar in magnitude to that for lung cancer. This finding suggests that residual confounding by smoking may have influenced the results, warranting cautious interpretations. No significant association was found between cumulative radiation exposure and all solid cancers after excluding lung cancer and mesothelioma, nor for IHD or CeVD. The marginally non-significant increased risk of Parkinson's disease, also seen in other Million Person Study cohorts, requires further investigation. Early workers monitored entirely before 1979 had the same linear ERR per 100 mGy for solid cancers [0.06 (0.00, 0.12) n = 3,587] as for all other more contemporary workers monitored after 1978 [0.07 (0.01,0.13) n = 4,150]. This report provides convincing evidence that low-dose and low-dose-rate exposures over time significantly increases the risk of leukemia (excluding CLL) following cumulative doses up to 200 mGy while also providing information on early versus contemporary workers.

Low GOPC mRNA expression is a novel candidate associated with increased risk of acute myeloid leukemia

Acute myeloid leukaemia (AML) risk stratification relies on cytogenetic and molecular abnormalities defined by European LeukemiaNet (ELN) 2022. Conventional cytogenetic techniques, including chromosomal banding analysis (CBA) and fluorescence insitu hybridization, have limited resolution and may miss cryptic events. Optical genome mapping (OGM) is a genome-wide approach capable of detecting balanced and unbalanced structural variants with high resolution, potentially revealing cryptic abnormalities of diagnostic and prognostic relevance. We retrospectively studied 100 adults with newly diagnosed AML, each showing one to two cytogenetic abnormalities and lacking the World Health Organization 2022-defining rearrangements or baseline ELN adverse karyotypes. OGM was performed to evaluate additional cytogenetic abnormalities and impact on ELN 2022 risk classification. Clinical outcomes were explored descriptively. OGM detected 91.4% of abnormalities identified by CBA and provided additional information in 37% (95% confidence interval: 28%-47%) of patients. Fourteen per cent was reclassified to an unfavourable cytogenetic group, and 7.7% was reclassified to ELN 2022 adverse risk. Cryptic KMT2A and NUP98 lesions were found in 10% of cases, highlighting potential therapeutic targets. Survival analyses suggested a trend towards poorer outcomes in patients reclassified as adverse, though the small sample limits definitive conclusions. In low-complexity AML, OGM provides substantial incremental diagnostic value, detecting cryptic high-risk and targetable abnormalities, supporting its use as a complementary tool.

Evaluation of exposure characteristics and radiological risks for cyclotron-based 18F radiopharmaceutical production workers in China.

Background: Optical genome mapping (OGM) detects genome-wide structural variants (SVs), including balanced rearrangements and complex copy-number alterations beyond standard-of-care cytogenomic assays. In chronic lymphocytic leukemia (CLL), cytogenetic and genomic risk stratification is traditionally based on fluorescence in situ hybridization (FISH), karyotyping, targeted next-generation sequencing (NGS), and immunogenetic assessment of immunoglobulin heavy chain variable region (IGHV) somatic hypermutation status, each of which interrogates only a limited aspect of disease biology. Methods: We retrospectively evaluated fifty patients with CLL using OGM and integrated these findings with cytogenomics, targeted NGS, IGHV mutational status, and clinical time-to-first-treatment (TTFT) data. Structural variants were detected using OGM and pathogenic NGS variants were derived from a clinical heme malignancy panel. Clinical outcomes were extracted from the electronic medical record. Results: OGM identified reportable structural variants in 82% (41/50) of cases. The most frequent abnormality was del(13q), observed in 29/50 (58%) and comprising 73% (29/40) of all OGM-detected deletions with pathologic significance. Among these, 12/29 (42%) represented large RB1-spanning deletions, while 17/29 (58%) were focal deletions restricted to the miR15a/miR16-1 minimal region, mapping to the non-coding host gene DLEU2. Co-occurrence of adverse lesions, including deletion 11q/ATM, BIRC3 loss, trisomy 12, and deletion 17p/TP53, were recurrent and strongly associated with shorter TTFT. OGM also uncovered multiple cryptic rearrangements involving chromosomal loci that are not represented in the canonical CLL FISH probe panel, including IGL::CCND1, IGH::BCL2, IGH::BCL11A, IGH::BCL3, and multi-chromosomal copy-number complexity. IGHV data were available in 37/50 (74%) of patients; IGHV-unmutated status frequently co-segregated with OGM-defined high-risk profiles (del(11q), del(17p), trisomy 12 with secondary hits, and complex genomes whereas mutated IGHV predominated in OGM-negative or structurally simple del(13q) cases and aligned with indolent TTFT. Integration of OGM with NGS further improved genomic risk classification, particularly in cases with discordant or inconclusive routine testing. Conclusions: OGM provides a comprehensive, genome-wide view of structural variation in CLL, resolving deletion architecture, identifying cryptic translocations, and defining complex multi-hit genomic profiles that tracked closely with clinical behavior. Combining OGM and NGS analysis refined risk stratification beyond standard FISH panels and supports more precise, individualized management strategies in CLL. Prospective studies are warranted to evaluate the clinical utility of OGM-guided genomic profiling in contemporary treatment paradigms.

Rationale:Congenital neutropenia (CN) encompasses a group of disorders characterized by impaired neutrophil differentiation, resulting in persistently low neutrophil counts in the peripheral blood. It presents with recurrent infections and an elevated risk of leukemia. Multiple genetic mutations have been implicated in the pathogenesis of neutropenia.Patient concerns:This paper reports the case of a 3-year-2-month-old boy admitted with a 4-day history of cough and fever, accompanied by recurrent respiratory infections, neutropenia, and growth retardation. Whole-exome sequencing identified a mutation in the caseinolytic peptidase B homolog (CLPB) gene (NM_030813.6: c.1681C>T: p.R561W).Diagnoses:Although the initial genetic sequencing did not reveal mutations consistent with the clinical presentation, the child continued to experience recurrent infections. Upon reanalysis, a pathogenic CLPB-related mutation was detected, leading to the diagnosis of CN.Interventions:During hospitalization, the patient received targeted antimicrobial therapy based on the identification of the pathogen. Following the confirmed diagnosis, he also received intermittent granulocyte colony-stimulating factor therapy.Outcomes:Administration of granulocyte colony-stimulating factor successfully maintained neutrophil counts above 0.5 × 109/L and significantly reduced the frequency of respiratory tract infections.Lessons:CLPB deficiency should be considered in pediatric patients presenting with CN and concurrent neurological symptoms, as early recognition allows for the timely initiation of appropriate treatment strategies and contributes to improved clinical outcomes.

BackgroundMaternal infections during pregnancy may increase the risk of childhood cancer (CC) in offspring by affecting foetal immunity and genetics. Existing evidence seems inconclusive, necessitating a comprehensive review to understand this association. We aimed to evaluate the risk of various CC outcomes following prenatal exposure to different types of maternal infections.MethodsWe searched Medline, Web of Science, Embase, Cochrane Library, and bibliographies for relevant studies from inception to October 2025. The study protocol was registered in PROSPERO (ID:CRD42023483706). We included original human epidemiological studies that examined the association between maternal infections during pregnancy and CC with appropriate reference groups and no language restrictions. We excluded studies if they were reviews or reports, if they did not assess individual-level infection or if they used therapies for infections (e.g., antibiotics) as markers of infection exposure. Two independent reviewers extracted data and assessed methodological quality following PRISMA guidelines. Pooled estimates (ES) and 95% confidence intervals (95%CIs) were calculated using random-effect models. Heterogeneity was examined in subgroup analyses. Publication bias was evaluated using Egger’s tests and Funnel plots.ResultsFrom 9284 studies identified by the search, 46 studies (39 case–control,7 cohort) with over nine million participants were included, covering 33 analyses of 12 types of infection and five CC sites. Overall, maternal infection during pregnancy was associated with increased risk of CC (ES = 1.36;95%CI,1.17–1.59). Sexually transmitted infections (STIs) were associated with increased overall CC risk (ES = 2.86;95%CI,1.88–4.33). Viral infections were also associated with increased risk of overall CC (ES = 1.43;1.18,1.74), with cytomegalovirus and rubella virus infections showing positive associations upon stratification by pathogen-type. Genitourinary tract infections (GUTIs) were associated with increased risk of leukaemia (ES = 1.49;95%CI,1.05–2.12) and solid tumours (ES = 1.60, 95%CI;1.06–2.42) and viral infections with the risk of acute lymphoblastic leukaemia (ES = 1.58;95%CI,1.15–2.18).ConclusionsMaternal STIs, GUTIs, and viral infections during pregnancy are associated with increased risk of CC, with GUTIs and viral infections specifically associated with increased risk of leukaemia. Targeted prevention strategies towards specific infections during pregnancy may protect against CC. Large-scale prospective studies with precise infection assessment and stratification by pathogen-type, and mechanistic considerations are needed to deepen knowledge in this area.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12916-026-04625-1.

Prenatal and postnatal exposure to traffic-related air pollution (TRAP) and childhood cancer: Systematic review and meta-analysis.

Traffic-related air pollution and childhood acute leukemia in France: GEOCAP nationwide case-control study.

Unveiling the therapeutic potential and leukemia risk of PD-166866 in sepsis via an integrated computational-experimental strategy.

Pathogenic germline variants in CHEK2 are associated with a moderately increased risk of several solid tumors; however, their contribution to myeloid malignancies remains poorly defined. We analyzed germline CHEK2 variants in 1,035 patients with acute myeloid leukemia (AML) and 283 with myelodysplastic syndromes (MDS). Pathogenic (P) and likely pathogenic (LP) variants were identified, and their frequency, type, and clinical context were evaluated, including family and personal cancer histories. P/LP CHEK2 variants were found in 1.74% of AML and 1.77% of MDS cases. While founder mutations such as c.1100delC and p.I157T were present, most were rare missense variants with a population allele frequency below 0.001. These variants were significantly enriched in AML and MDS, even after adjusting for ethnicity. Notably, 39% of AML patients with P/LP CHEK2 variants had a history of solid tumors or hematologic malignancies. Family history of cancer was also frequent, with 21% reporting hematologic and 57% reporting solid tumors. Our findings support an expanded role for germline CHEK2 variants in predisposing individuals to myeloid neoplasms, in addition to their association with solid tumor risk. Given the emerging evidence linking CHEK2 to clonal hematopoiesis, these results underscore the need for prospective studies to refine risk assessment, inform genetic counseling, and guide surveillance strategies. These results suggest that clinical guidelines may consider monitoring clonal hematopoiesis in CHEK2 carriers and weighing in risk and benefit when considering CHEK2 carriers as stem cell transplant donors.

Pediatric Leukemia is the most common childhood cancer, yet its exact causes remain unclear. Both genetic predisposition and host biological factors may influence susceptibility. ABO and Rhesus (Rh) blood group systems, beyond their role in transfusion compatibility, have been linked to the risk of various cancers through mechanisms involving immune response, cell adhesion, and inflammation. Family history of malignancy is another established risk marker, reflecting shared genetic and environmental influences. Objectives of the study is to investigate the combined influence of ABO and Rh blood group types and family history of malignancy on the risk of developing pediatric leukemia. The current study was conducted on 50 patients with leukemia of all kinds in the Central Teaching Hospital of Pediatrics in Baghdad, Iraq. The diagnosis was confirmed based on bone marrow aspiration and blood film. ABO and Rh blood group was tested manually for all patients, and Family history was determined through the medical records. The blood groups were predominantly O+ (20; 40%), followed by B+ (12; 24%), A+ (10; 20%), AB+ (7; 1%), and O- (1; 2%), respectively. The analysis of family history regarding cancer in the patient samples revealed that a majority of children with leukemia had a negative family history, compared to those with a positive family history (80% vs. 20%). Furthermore, the majority of the case group's leukemic children were evaluated and classified as being at standard (low) risk (42%), with high and intermediate risks coming in second and third, respectively, at 36% and 22%. This study highlights that pediatric leukemia risk patterns differ by subtype, with predominance of low-risk classifications in B-ALL, ALL, and AML, while T-ALL cases were uniformly high-risk. The findings suggest that ABO blood group and family history may influence leukemia susceptibility and prognosis in a subtype-specific manner, blood group O and Rh D positive are risk factors for the incidence of ALL in children underscoring the need for larger studies to clarify these associations

This study investigates the contamination of sweet potatoes by 137Cs following a hypothetical radiological dispersion event, assessing its implications for food safety and public health. Given the increasing concerns about nuclear energy expansion, this research is particularly relevant to agricultural systems, which are crucial to food security. Using HotSpot Health Physics Codes (v3.1.2), we simulated the radionuclide dispersion in a sweet potato farming area, considering environmental factors like atmospheric stability and soil properties. The model assesses the transfer of radioactive material to crops and the potential health risks to consumers. The evaluation links 137Cs exposure to an increased risk of leukemia, represented by the excess risk of its fatal occurrence over a lifetime, emphasizing the need for post-radiological incident monitoring. The results of the simulations suggest, for example, that the concentration of activity of 137Cs in the root of the sweet potato can vary by up to 3 orders of magnitude for the same location, depending on variations in the local atmospheric stability classes. Such sensitivity was also observed for the risk of developing radiation-induced leukemia, whose average values for the adopted radionuclide-to-plant Transfer Factors models may differ by up to 2 orders of magnitude depending on the same variables. Through computational modeling, this study offers insights into the threat posed by radiological contaminants in food chains and underscores the importance of surveillance measures in protecting public health.

Birth defects are associated with increased cancer risk in the general pediatric population, yet their impact on leukemia risk in children with Down syndrome (DS) remains uncertain. We assessed this using data from 26,660 children with DS in the Genetic Overlap Between Anomalies and Cancer in Kids Registry Linkage Study. Among them, 71.9% had at least one major birth defect, predominantly involving the cardiac (64.2%), musculoskeletal (21%), and gastrointestinal systems (6.8%). The cumulative incidence of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) was comparable in children with and without co-occurring defects. Adjusted hazard ratios (aHR) for ALL and AML in children with versus without co-occurring major birth defects were 1.12 (95% confidence interval [CI]: 0.80-1.56) and 1.09 (95% CI: 0.76-1.58), respectively. Overall, no consistent patterns were seen between organ system-level defects and ALL. However, in terms of specific defects, we identified that anophthalmia/microphthalmia (aHR: 2.83, 95% CI: 1.16-6.92) was associated with ALL and tetralogy of Fallot (aHR: 2.40, 95% CI: 1.27-4.55) was associated with AML. While children with DS experience a higher prevalence of birth defects, these defects do not appear to strongly influence leukemia risk, unlike the elevated risk observed in the general pediatric population (< 18years).

"Sickle cell trait and the risk for malignancy".

Recent advances in formaldehyde adsorption by metal-organic frameworks for indoor air filtration.

Increased leukemia incidence or mortality is a well-known effect of acute radiation exposure. Less is known about the risks associated with protracted exposure, such as those arising in occupational exposure settings. We used excess relative risk models to investigate the strength of evidence for and the shape of the dose response for mortality from leukemia (excluding chronic lymphocytic leukemia, CLL) in the Russian Mayak Worker Cohort. The cohort includes 25,757 workers followed for cancer mortality from 1948 to 2015 who were subject to both external low-dose-rate gamma ray and internal exposures (from alpha particles emitted by inhaled plutonium). The red bone marrow external dose estimates were based on individual readings from film badges or TLD dosimeters. The mean external marrow dose was 584 mGy for workers hired before 1959 and 105 mGy for those hired between 1959 and 1982. Internal exposures were described using red bone marrow alpha-particle dose for workers who were subject to plutonium monitoring and potential plutonium exposure categories for unmonitored workers. The mean marrow dose from internal exposure for monitored workers was 2.1 mGy for those hired before 1959 and 0.16 mGy for those hired between 1959 and 1982. Radiation effects were described using both excess relative rate (ERR) and excess absolute rate (EAR) models. The excess relative rates for the 96 deaths from non-CLL leukemia were described using a time-since-exposure-dependent quadratic response in cumulative external low LET dose with effect modification by attained age. While the largest ERRs [2.45 at 1 Gy, 95% confidence interval (CI) 0.33 to 11.9] were associated with external doses received between 2 and 5 years before death, there was also a significant increase in rates for doses received 5 or more years before death (ERR 0.28 at 1 Gy, 95% CI 0.06 to 0.72) and an indication of increased rates associated with doses within two years of death (ERR 1.47 at 1 Gy, 95% CI 0.06 to 10.6). Uncertainties in these excess relative rate estimates from the primary models were adjusted for dose uncertainty. Excess absolute rate (EAR) models were also used to describe the leukemia death rates. The pattern of the EAR variation with time-since-exposure was like that for the ERR Doses received 2 to 4 years before death had the largest EAR (ERR 4.78 per 10,000 person years per Gy2, 94% CI 1.75 to 10.7) with increased rates for doses received within two years of death (3.66, 95% CI 9.26 to 11.2), and for doses received 5 or more years before death (0.34, 95% CI 0.11 to 0.7). However, while the ERR decreased with increasing attained age, there was no indication of an attained age dependence in the EAR. The external-exposure radiation-associated leukemia risk appeared to be largely from acute myeloid leukemia. There was no evidence of external exposure effects on the risks of death from chronic lymphocytic leukemia, lymphoma, or multiple myeloma. There was no evidence of internal exposure effects on the rates of leukemia or other lymphohematopoietic malignancies. These analyses extend earlier studies of leukemia mortality in the Mayak worker cohort, with additional years of follow-up, utilize the latest bone marrow dose estimates, and include an assessment of the effect of shared dose uncertainty on risk uncertainty. Our results show significant excess risk for non-CLL leukemia mortality with a complex interaction between attained age, time since exposure, and age at exposure. The highest risk per unit dose was associated with exposures received 2-5 years before the time at risk. In addition, for a given total cumulative dose, the risk decreases rapidly with increasing attained age. We discuss the differences between the patterns of risk related to acute exposures in the Life Span Study of survivors of the atomic bombings in Hiroshima and Nagasaki, and chronic exposure in the Mayak Worker Cohort as well as differences between risk estimates in our study and others involving prolonged low-dose external gamma ray exposure.

Abnormal circulating lipid levels have been suggested in relation to lymphoid malignancy (LM) risk. We studied UK Biobank participants (n = 403,625) with serum data for cholesterol (total [TC], high-density lipoprotein [HDL], direct low-density lipoprotein [LDL]), triglycerides (TG), and apolipoproteins A1 and B (ApoA1, ApoB). We conducted principal component (PC) analysis and multivariate Cox regression models to estimate hazard ratio (HR) overall, by lipid-lowering drug use and follow-up interval. During an average of 10.5 years of follow-up, 3006 incident LMs occurred (including 667 multiple myelomas [MM], 2193 non-Hodgkin lymphomas [NHL]). Among medication non-users, most lipid levels were inversely associated with risk of most endpoints (HRQ4vsQ1range: 0.37 to 0.79), especially closer to diagnosis. In contrast LDL/HDL ratio and PC1 (highly loaded in LDL and ApoB) were consistently positively associated with chronic/small lymphocytic leukaemia risk in each follow-up period and with NHL and B-cell NHL risk within 5 years. Further, LD, ApoB and TG levels were positively associated with MM risk after 10+ years (HR1-SDrange = 1.26 to 1.60). Lipid depletion closer to LM diagnosis might reflect cancer cell metabolism and warrants further work examining individuals with precursor conditions. The MM-specific long-term risk might reflect the known MM-obesity association.

Sickle cell disease (SCD) is a hemoglobinopathy characterized by hemolysis, vaso-occlusion, and systemic inflammation. Epidemiological studies identified an increased risk of leukemia, especially acute myeloid leukemia (AML), in individuals with SCD, whereas data regarding other tumors are conflicting. SCD-associated AMLs frequently display high-risk features with unfavorable karyotypes and a dismal prognosis. SCD is associated with multiple phenomena linked to carcinogenesis in other contexts, including chronic inflammation, oxidative stress, ineffective erythropoiesis, accelerated hematopoietic aging, impaired tumor immunosurveillance, and increased clonal hematopoiesis. The role and respective contribution of these disease-intrinsic mechanisms in SCD remain to be studied. Although therapies used in SCD could theoretically modulate the risk of malignancies, no data exist to support an increased or reduced risk associated with their use. The most notable exception is hematopoietic stem cell transplantation and, to a lesser extent, gene therapy, for which the conditioning and/or procedure itself is known to increase the risk of leukemia. In sum, the effect of SCD on carcinogenesis is an emerging area of investigation with data supporting specificities in SCD-associated AML. Future research is required to determine the role of treatments to mitigate the increased risk and improve the outcome of SCD-associated AML.

Acute leukemia is the most common type of cancer in children; however, the etiology is poorly understood. The objective of this review was to summarize the current evidence of the role of perinatal factors in the development of acute leukemia. All epidemiological studies published up to October 2023 that evaluated perinatal risk factors for childhood acute leukemia were identified using a multi-tiered approach in two electronic databases (PubMed and Web of Science), without restriction on publication year or language. A total of 85 studies (13 prospective cohort studies, 62 case-control studies, and 10 pooled analyses) were included. We combined the published risk estimates in a meta-analysis, using the Generic Inverse Variance method. An increased risk of acute leukemia and the lymphoblastic subtype (ALL) was associated with high birth weight (>4000 g) (odds ratio [OR] = 1.35; 95% confidence interval [95% CI] 1.20-1.53 and OR = 1.21; 95% CI 1.08-1.34, respectively), maternal history of abortion (OR = 1.27; 95% CI 1.12-1.43 and OR = 1.24; 95% CI 1.08-1.43, respectively), and maternal diabetes (OR = 1.30; 95% CI 1.14-1.48 and OR = 1.32; 95% CI 1.16-1.50, respectively). In addition, an increased risk for ALL was also associated with maternal hypertension (OR = 1.21; 95% CI 1.06-1.38) and cesarean section (OR = 1.10; 95% CI 1.05-1.16). Our review suggests a potential role for perinatal factors in the development of acute leukemia in children. These findings indicate potential avenues for developing cost-effective prevention strategies applicable at the population level, while the mechanism of action is investigated.