Childhood leukemia remains a critical public health concern, necessitating comprehensive evaluations of environmental risk factors. This systematic review aims to evaluate the epidemiological evidence regarding the relationship between combined oil exposure during pregnancy and childhood and an increased risk of childhood leukemia, thereby contributing to improved overall childhood health. The review focused on children diagnosed with leukemia. Following the guidelines set forth by the Cochrane Handbook for Systematic Reviews of Interventions' instructions, we conducted a systematic review. Three databases (PubMed, Google Scholar, and Medline) were thoroughly searched to find research that was up to May 31, 2025. Two independent reviewers screened the literature by using Covidence software. The methodological quality and potential for bias in each included case-control and cohort study were systematically evaluated using the Quality Assessment Tool integrated within Covidence software. We assessed the overall quality of evidence using AMSTAR 2, a widely used instrument for critically appraising systematic reviews. In total, 13 studies were included in this review: 11 case-control and 2 cohort studies with an overall sample size of 2,808,870 individuals. Four studies indicated a statistically significant association between maternal and paternal exposure to "gasoline, benzene, diesel exhaust, oil, mineral oil, and gas" and an increased likelihood of childhood leukemia. One study indicated that the association with petrol compound exposure appeared stronger for acute myeloid leukemia (AML) than for acute lymphoblastic leukemia (ALL). Multiple studies reported positive associations between different petroleum compound exposures and childhood leukemia. In conclusion, the current review pointed toward an association between exposure to petrol compounds and a higher risk of childhood leukemia. Therefore, we recommend implementing stricter environmental regulations on benzene emissions and establishing evidence-based safety buffer zones between petrol stations and residential areas. Furthermore, routine air quality monitoring near these sites is essential to safeguard pediatric health.

BackgroundIndividuals with Down syndrome have an elevated risk of childhood leukaemia and are suggested to have a reduced risk of solid tumours in adulthood. However, it remains unclear which cancer subtypes contribute to this pattern and the lifetime cancer risk.MethodsThis Swedish population-based matched cohort study investigated age- and subtype-specific cancer risks in Down syndrome. National healthcare registers were used to include 9742 individuals with Down syndrome, born in Sweden between 1930–2017. Each individual was matched by birth year, sex, and birth county to 50 comparisons. Hazard ratios (HRs) and 95% confidence intervals (95% CI) were calculated using Cox proportional hazard models.ResultsChildren with Down syndrome had a 20-fold increased risk of acute lymphoblastic leukaemia (ALL), and nearly a 500-fold increased risk of acute myeloid leukaemia (AML) before the age of 5. In contrast, individuals with Down syndrome had an overall lower risk of solid tumours, with significantly decreased risks for breast, prostate, lung, colorectal, gynaecological cancers, and melanoma, in adults. However, an increased risk was observed for testicular cancer and chondrosarcoma/chondroblastoma.ConclusionWe present the most comprehensive profile of cancer risk in Down syndrome, aiming to guide clinical practices, encourage tailored surveillance recommendations, and incite research on chromosome 21’s role in oncogenesis.

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).

Association between exposure to PM2.5 and black carbon and the risk of childhood leukemia in Tehran: A case-control study with critical exposure time windows.

Beyond clonal hematopoiesis of indeterminate potential: Understanding how the trisomy 21 context promotes TET2 mutations

Traffic-related air pollution exposure at birth and risk of childhood leukemia: results from the GEOCAP-Birth case–control study

Epidemiological studies have shown a small but significantly increased risk of leukemia in children conceived by in vitro fertilization. Atypical DNA methylation patterns observed in pediatric cancers are suspected to occur in utero, and it is known that periconceptional conditions linked to assisted reproductive technologies (ART) are responsible for DNA methylation modifications. Using databases and systematic literature screens, we derived a list of cancer/leukemia genes (n = 1246 and n = 532 genes, respectively, corresponding to 1466 individual genes) and of differentially methylated genes (DMG) in leukemia (n = 2642) and pre-leukemia (n = 381). These lists were cross-referenced with DMG (n = 93) curated from 18 ART Epigenome-Wide Association Studies (EWAS) (2369 samples). Among the ART DMG, more than one-third (n = 33) were leukemia, and six were pre-leukemia DMG, all representing a significant enrichment. Seven of the enriched genes (NTM, PRSS16, SCAND3, SYCP1, TP73, ZNF184, and ISL1-DT) showed concordant methylation between ART and leukemia/pre-leukemia. Moreover, five of the ART DMG are known targets for somatic/germline alterations in leukemia: ATP10A, CHD2, FBRSL1, FGFR2, and SORCS1. The ART DMG were not significantly enriched in cancer genes, supporting the hypothesis that ART may not link broadly to any cancer type but rather to leukemia. This study indicates that relatively few genes that are known targets for somatic/germline mutation in cancer experience DNA methylation changes in individuals conceived through ART. By contrast, DNA methylation disturbances reported in leukemia represent more than one-third of those associated with ART conception, thus raising the question of their role in leukemia risk in ART-conceived individuals. Among them, a few critical genes such as TP73, a tumor suppressor, were shown to be targeted for hypermethylation, both in ART and leukemia, warranting further investigation.

Environmental exposure to extremely low frequency magnetic fields (ELF-MF) is suspected of being a risk factor of childhood acute leukemia (AL) and classified as possible carcinogen. Results of recent epidemiological studies remain however heterogeneous. The present study aimed to evaluate AL risk in children exposed to ELF-MF by living close to high-voltage overhead power lines (HVOL) in France. We included 4117 AL cases under the age of 15 diagnosed in 2002-2010 and 44,838 contemporary controls representative of the French pediatric population, drawn from the national registry-based GEOCAP study. The distance between the geocoded address of residence and the closest 63-400kV HVOL, and the closest 225-400kV HVOL, were evaluated. ELF-MF exposure was also calculated at the geocoded addresses considering the characteristics of the neighboring HVOLs. Logistic regression models adjusted for age were used to estimate odds-ratios (OR) and 95% confidence intervals. Sensitivity analyses were carried out to account for geocoding error and potential confounders. 0.7% of the controls lived within 50m of HVOL and 0.3% were exposed to more than 0.3μT. Living within 50m of HVOL was associated with an increased risk of AL for children under 5 (OR=1.6 (1.0-2.7)), an association more marked when restricting to the high-quality geocoded addresses (OR=3.2 (1.3-7.9)). ELF-MF was not associated with AL risk (≥0.3μT, OR=0.6 (0.3-1.3)). The results remained stable in all the sensitivity analyses. Our study brings new evidence that ELF-MF are probably not associated with AL risk, and cannot explain an association with distance to HVOL.

Prenatal exposure to air pollution and pediatric acute leukemia: A nationwide study.

Can Breastfeeding Lower the Risk of Childhood Leukemia? Insights from a Duhok Study, Iraq. Case control study

Background:Children living in upstream oil and natural gas (O&G) areas may be exposed to leukemogens and at increased risk for acute lymphoblastic leukemia (ALL).Methods:We conducted a case–control study of children born in Colorado between 1992 and 2019. We matched 451 children diagnosed with ALL at ages 2 to 9 years starting in 2002 to 2,706 controls based on birth month/year and Hispanic ethnicity. We estimated upstream O&G activity intensities from conception through a 10-year latency using our intensity-adjusted inverse distance weighted (IA-IDW) model. We applied logistic regression models adjusted for confounders to evaluate associations between ALL and IA-IDW.Results:For children within 5 km of an O&G well site, we observed a 62% [OR = 1.62; 95% confidence interval (CI), 0.964–2.62], 84% (OR = 1.84; 95% CI, 1.35–2.48), and 100% (OR = 2.00; 95% CI, 1.14–3.37) increase in ALL risk for low, medium, and high IA-IDW groups, compared with the referent group. Within 13 km, we observed a 59% (OR = 1.59; 95% CI, 1.03–2.37), 40% (OR = 1.40; 95% CI, 1.09–1.80), and 164% (OR = 2.64; 95% CI, 1.80–3.86) increase in ALL risk for low, medium, and high IA-IDW groups.Conclusions:Colorado’s children living within 13 km of O&G well sites are at increased risk for ALL, with children within 5 km bearing the greatest risk. Current setbacks between O&G well sites and residences may not be sufficient to protect the health of these children.Impact:Our results can be applied to policies to reduce childhood leukemogen exposures.

Leukemia is the most common pediatric cancer, affecting 33% of children globally. Genetic mutations and environmental factors increase the risk of developing pediatric leukemia. Mutations of the genes RUNX1, TP53, and BRCA1 increase risk by disrupting cell differentiation and proliferation and impairing deoxyribonucleic acid (DNA) repair. Environmental risk factors (i.e., ionizing radiation, benzene, and pesticides) disrupt DNA replication and cell growth, often leading to genetic mutations. This literature review explores both the genetic and environmental risk factors of pediatric leukemia. We searched peer-reviewed references using Google Scholar. Findings illustrate the interplay between DNA mutations and environmental influences. Specifically, RUNX1 mutations and pesticide exposure, particularly benzene, disrupt DNA replication. Individuals with a RUNX1 mutation are at a higher risk of developing leukemia, particularly if exposed to pesticides, highlighting the impact of environmental factors on the increased risk of leukemia. Researchers and health professionals should consider the interplay between genetic mutations and environmental factors when evaluating the risk of childhood leukemia. Testing children for exposure to environmental factors may allow for early diagnosis and tailored treatment and prevention interventions for children with higher susceptibility to developing leukemia.

The few epidemiologic studies of infection exposure in early life and acute leukemia (AL) risk in Latino children have yielded inconsistent results, suggesting a possible effect of ethnicity. Here, we examined the correlation between infection exposure and acute leukemia risk in children from Mexico City-One of the biggest Latino cities worldwide. This study included 1455 Mexican children diagnosed with de novo AL (2002-2016), and 1455 control individuals frequency-matched by age and health institution. The AL population included acute lymphoblastic leukemia (ALL), Pre-B ALL, and acute myeloblastic leukemia (AML). Logistic regression analyses were performed to investigate direct and indirect proxies of infection in children or their mothers. Upper respiratory tract infections during the child's first year of life were a risk factor for AL (OR, 2.76; 95% CI, 1.48-5.15), including ALL (OR, 3.14; 95% CI, 1.67-5.89) and Pre-B (OR, 3.11; 95% CI, 1.63-5.96). Mother's infections before and during pregnancy were protective factors against AL (OR, 0.55; 95% CI, 0.47-0.64; and OR, 0.61; 95% CI, 0.52-0.72, respectively). These associations included ALL and Pre-B. In contrast, only mothers' infections before pregnancy and respiratory tract infections were protective factors against AML (OR, 0.45; 95% CI, 0.33-0.62; and OR, 0.50; 95% CI, 0.37-0.68, respectively). Infections during the first year of life were associated with AL development in children of Mexico City. Additionally, mothers' exposure to respiratory tract infections before and during pregnancy reduced the AL risk in this Latino population.

Maternal use of hormonal contraception and risk of childhood leukemia: A Scandinavian population-based cohort study.

Often relying on mother's recollections of past events, the possible relationship between maternal illness in pregnancy and risk of malignancy in their offspring has long been a focus of research. Free from recall bias, this study of childhood cancer (0–14 years) examined these associations using data abstracted from mothers' primary‐care (1623 cases, 2521 controls) and obstetric (2721 cases, 5169 controls) records. Maternal infections and other illnesses in pregnancy were examined for any possible associations with childhood leukaemia, lymphoma, CNS or embryonal tumours using pooled information from the two medical record sources (2885 cases and 5499 controls), accounting for potential confounders. Maternal anaemia was associated with childhood acute myeloid leukaemia (AML) (odds ratio, OR = 2.07, 95%CI [1.40–3.08]). Anaemia during pregnancy was also recorded more frequently in the notes of mothers of children with medulloblastoma, retinoblastoma and embryonal rhabdomyosarcoma: ORs 2.36 [1.36–4.11], 1.83 [1.01–3.33] and 2.91 [1.64–5.16] respectively. Other associations included urinary tract infections (UTIs) and non‐Hodgkin lymphoma (NHL); preeclampsia and NHL; and polyhydramnios with both AML and NHL. No evidence was found to suggest that influenza during pregnancy impacted on childhood leukaemia risk. In conclusion, our findings are supportive of an association between maternal anaemia in pregnancy and childhood AML, and maternal anaemia and embryonal tumours; underscoring the need for further research exploring the potential causes and roles of iron and vitamin deficiencies. Due to small numbers and lack of corroborative evidence, the associations observed for UTIs, preeclampsia, and polyhydramnios must be treated cautiously.

Gestational Epigenetics and Risk of Childhood Leukemia

Domestic radon exposure and childhood cancer risk by site and sex in 727 counties in the United States, 2001–2018

Objective: The aim of this study was to test the hypothesis that the duration of breastfeeding in infancy reduces the risk of childhood leukemia or lymphoma, and modifies the risk of developing functional gastrointestinal disorders (FGIDs). Subjects and Methods: This case-control study involved the recruitment of children with lymphoid malignancy and functional gastrointestinal symptoms with healthy children as controls. Focused questionnaires were used to collect data on breastfeeding history and other key risk factors. Univariate and multivariate analyses were undertaken. Results: Of the 334 children with lymphoid malignancy, 65% were male. The control group included 334 age- and sex-matched participants. Most (n = 189; 56.6%) of the children with leukemia were <10 years of age. Differences between cases and controls included the duration of breastfeeding (p < 0.0001), mean birthweight (p < 0.001), maternal age (p < 0.001), paternal age (p < 0.001), birth order (p < 0.001), mean number of children (p < 0.001), BMI percentile (p = 0.042), and maternal smoking (p = 0.012). Breastfeeding duration of up to 6 months' duration, when compared with feeding of longer than 6 months, was associated with increased odds ratios (OR) for acute lymphoblastic leukemia (OR = 3.43, 95% confidence interval [CI] 2.37-4.98; p < 0.001), Hodgkin's lymphoma (OR = 1.58, 95% CI: 0.88-2.84, p = 0.120), Non-Hodgkin's lymphoma (OR = 2.14, 95% CI: 1.25-3.65, p = 0.005), and overall (OR = 1.95, 95% CI: 1.40-2.71, p < 0.001). Cases also differed from controls with regard to FGIDs, such as stomach ache (p < 0.001), dyspepsia (p < 0.001), early satiety (p = 0.017), bowel satisfaction (p < 0.001), bloating (p < 0.001), nausea (p = 0.005), vomiting (p = 0.039), constipation (p = 0.003), diarrhea (p = 0.010), gastrointestinal canal congestion (p =0.039), muscle aches pains (p = 0.008), fecal incontinence (p = 0.021), and indigestion (p = 0.003). A multivariate stepwise regression analysis revealed that maternal smoking (p < 0.001), formula feeding (p < 0.001), duration of breastfeeding (p < 0.001), birth order (p = 0.002), mother's age (p = 0.004) and the child's birthweight (p = 0.009) were predictors for leukemia. Further analysis showed that dyspepsia (p < 0.001), gastrointestinal tract canal congestion (p < 0.001), constipation (p = 0.009), diarrhea (p = 0.013), bowel satisfaction (p = 0.021), bloating (p = 0.022), duration of breastfeeding (p < 0.001), and stomach ache (p = 0.025) were significant predictors for developing FGID symptoms after adjusting for age, gender, and other confounding variables. Conclusion: This study confirmed that breastfeeding has some effect on reducing possible risk of childhood lymphoma and leukemia and FGID symptoms compared with healthy control children.

Leukemia is the most common childhood cancer and its etiology could be related to various environmental contaminants such as particulate matter (PM). The objective of our study is to evaluate the potential association between exposure to PM during pregnancy and the incidence of childhood leukemia. We established a population-based nationwide cohort using the Spanish Birth Registry Statistics database of the National Statistics Institute. We used spatiotemporal land use random forest models to estimate the concentrations of PM10 and PM2.5 for the entire pregnancy and by trimesters. We conducted logistic regression analyses adjusted for various covariates. In addition, we fitted generalized additive models (GAMs) to estimate the non-linear relationship between PM levels and leukemia incidence. The study included 3,112,123 children and 1066 cases of leukemia. The results for the continuous variable of PM10 exposure levels suggested an increased risk of childhood leukemia to be associated with higher exposure. The results for the categorized PM10 variable suggest an increased risk of childhood leukemia among pregnant women whose exposure levels were higher than the median (third and fourth quartiles). The results for PM2.5 were weaker. We found association between exposure to PM10 during pregnancy and an increased risk of childhood leukemia. Our findings indicate that public health interventions should aim to reduce air pollution to lower the incidence of childhood leukemia.

Leukemia is the most common cancer in children. Its incidence has been increasing worldwide since 1910th, suggesting the presence of common sources of the disease, most likely related to people's lifestyle and environment. Understanding the relationship between childhood leukemia and environmental conditions is critical to preventing the disease. This discussion article examines established potentially-carcinogenic environmental factors, such as vehicle emissions and fires, alongside space weather-related parameters like cosmic rays and the geomagnetic field. To discern the primary contributor, we analyze trends and annual variations in leukemia incidence among 0-14-year-olds in the United States, Canada, Australia, and Russia from 1990 to 2018. Comparisons are drawn with the number of vehicles (representing gasoline emissions) and fire-affected land areas (indicative of fire-related pollutants), with novel data for Russia introduced for the first time. While childhood leukemia incidence is rising in all countries under study, the rate of increase in Russia is twice that of other nations, possibly due to a delayed surge in the country's vehicle fleet compared to others. This trend in Russia may offer insights into past leukemia levels in the USA, Canada, and Australia. Our findings highlight vehicular emissions as the most substantial environmental hazard for children among the factors examined. We also advocate for the consideration of potential modulation of carcinogenic effects arising from variations in cosmic ray intensity, as well as the protective role of the geomagnetic field. To support the idea, we provide examples of potential space weather effects at both local and global scales. The additional analysis includes statistical data from 49 countries and underscores the significance of the magnetic field dip in the South Atlantic Anomaly in contributing to a peak in childhood leukemia incidence in Peru, Ecuador and Chile. We emphasize the importance of collectively assessing all potentially carcinogenic factors for the successful future predictions of childhood leukemia risk in each country.