Exploring Urban Green Spaces' Effect against Traffic Exposure on Childhood Leukaemia Incidence.

BACKGROUND: Several environmental factors seem to be involved in childhood leukaemia incidence. Traffic exposure could increase the risk while urban green spaces (UGS) exposure could reduce it. However, there is no evidence how these two factors interact on this infant pathology. OBJECTIVES: to evaluate how residential proximity to UGS could be an environmental protective factor against traffic exposure on childhood leukaemia incidence. METHODS: A population-based case control study was conducted across thirty Spanish regions during the period 2000-2018. It included 2526 incident cases and 15,156, individually matched by sex, year-of-birth, and place-of-residence. Using the geographical coordinates of the participants' home residences, a 500 m proxy for exposure to UGS was built. Annual average daily traffic (AADT) was estimated for all types of roads 100 m near the children's residence. Odds ratios (ORs) and 95% confidence intervals (95% CIs), UGS, traffic exposure, and their possible interactions were calculated for overall childhood leukaemia, and the acute lymphoblastic (ALL) and acute myeloblastic leukaemia (AML) subtypes, with adjustment for socio-demographic covariates. RESULTS: We found an increment of childhood leukaemia incidence related to traffic exposure, for every 100 AADT increase the incidence raised 1.1% (95% CI: 0.58-1.61%). UGS exposure showed an incidence reduction for the highest exposure level, Q5 (OR = 0.63; 95% CI = 0.54-0.72). Regression models with both traffic exposure and UGS exposure variables showed similar results but the interaction was not significant. CONCLUSIONS: Despite their opposite effects on childhood leukaemia incidence individually, our results do not suggest a possible interaction between both exposures. This is the first study about the interaction of these two environmental factors; consequently, it is necessary to continue taking into account more individualized data and other possible environmental risk factors involved.

Exploring Blue Spaces' Effects on Childhood Leukaemia Incidence: A Population-Based Case-Control Study in Spain.

BACKGROUND: Blue spaces have been a key part of human evolution, providing resources and helping economies develop. To date, no studies have been carried out to explore how they may be linked to paediatric oncological diseases. OBJECTIVES: To explore the possible relationship of residential proximity to natural and urban blue spaces on childhood leukaemia. METHODS: A population-based case-control study was conducted in four regions of Spain across the period 2000-2018. A total of 936 incident cases and 5616 controls were included, individually matched by sex, year of birth and place of residence. An exposure proxy with four distances (250 m, 500 m, 750 m, and 1 km) to blue spaces was built using the geographical coordinates of the participants' home residences. Odds ratios (ORs) and 95% confidence intervals (95%CIs) for blue-space exposure were calculated for overall childhood leukaemia, and the acute lymphoblastic (ALL) and acute myeloblastic leukaemia (AML) subtypes, with adjustment for socio-demographic and environmental covariates. RESULTS: A decrease in overall childhood leukaemia and ALL-subtype incidence was found as we came nearer to children's places of residence, showing, for the study as a whole, a reduced incidence at 250 m (odds ratio (OR) = 0.77; 95%CI = 0.60-0.97), 500 m (OR = 0.78; 95%CI = 0.65-0.93), 750 m (OR = 0.80; 95%CI = 0.69-0.93), and 1000 m (OR = 0.84; 95%CI = 0.72-0.97). AML model results showed an increasing incidence at closest to subjects' homes (OR at 250m = 1.06; 95%CI=0.63-1.71). CONCLUSIONS: Our results suggest a possible association between lower childhood leukaemia incidence and blue-space proximity. This study is a first approach to blue spaces' possible effects on childhood leukaemia incidence; consequently, it is necessary to continue studying these spaces-while taking into account more individualised data and other possible environmental risk factors.

Neuroblastoma in Spain: Linking the national clinical database and epidemiological registries - A study by the Joint Action on Rare Cancers.

PURPOSE: Linkage between clinical databases and population-based cancer registries may serve to evaluate European Reference Networks' (ERNs) activity, by monitoring the proportion of patients benefiting from these and their impact on survival at a population level. To test this, a study targeting neuroblastoma (Nb) was conducted in Spain by the European Joint Action on Rare Cancers. MATERIAL AND METHODS: Subjects: Nb cases, incident 1999-2017, aged < 15 years. Linkage included: Spanish Neuroblastoma Clinical Database (NbCDB) (1217 cases); Spanish Registry of Childhood Tumours (RETI) (1514 cases); and 10 regional population-based registries (RPBCRs) which cover 33% of the childhood population (332 cases). Linkage was semiautomatic. We estimated completeness, incidence, contribution, deficit, and 5-year survival in the databases and specific subsets. RESULTS: National completeness estimates for RETI and NbCDB were 91% and 72% respectively, using the Spanish RPBCRs on International Incidence of Childhood Cancer (https://iicc.iarc.fr/) as reference. RPBCRs' specific contribution was 1.6%. Linkage required manual crossover in 54% of the semiautomatic matches. Five-year survival was 74% (0-14 years) and 90% (0-18 months). CONCLUSIONS: All three databases were incomplete as regards Spain as a whole and should therefore be combined to achieve full childhood cancer registration. A unique personal patient identifier could facilitate such linkage. Most children have access to Nb clinical trials. Consolidated interconnections between the national registry and clinical registries (including ERNs and paediatric oncology clinical groups) should be established to evaluate outcomes.

Cadmium (Cd) and Lead (Pb) topsoil levels and incidence of childhood leukemias.

There are few well-established risk factors for childhood leukemias. While the frequency of childhood leukemias might be partially attributable to some diseases (accounting for a small fraction of cases) or ionizing radiation, the role of heavy metals has not been assessed. The objective of our study was to assess the potential association between levels of cadmium (Cd) and lead (PB) in soil and childhood leukemias incidence. We conducted a population-based case-control study of childhood leukaemia in Spain, covering 2897 incident cases gathered from the Spanish Registry of Childhood Tumours and including 14 Spanish Regions with a total population of 5,307,433 children (period 1996-2015). Cd and Pb bioavailable levels at every children's home address were estimated using data from the Geochemical Atlas of Spain. We used logistic regression to estimate odds ratios (ORs) and their 95% confidence intervals (95%CIs); we included as covariates: sex, rurality, employment rate and socioeconomic status. Metal levels were analysed according to two definitions: as continuous variable assuming linearity and as categorical variables to explore a potentially nonlinear association (quantiles). Increases in both Cd and Pb topsoil levels were associated with increased probability of childhood leukemias incidence. The results for the models with the continuous variables showed that a unit increase on the topsoil level was associated with an OR of 1.11 for Cd (95%CI 1.00-1.24) and an OR of 1.10 for Pb (95%CI 0.99-1.21). Our study may point towards a possible link between residential Cd and Pb topsoil levels and the probability of childhood leukemias incidence. Residing in a location with the highest concentrations of these heavy metals compared to those locations with the lowest could increase the risk around a 20%, for both Cd and Pb.

Risk factors for central nervous system tumors in children: New findings from a case-control study.

BACKGROUND: Central nervous system tumors (CNS) are the most frequent solid tumor in children. Causes of CNS tumors are mainly unknown and only 5% of the cases can be explained by genetic predisposition. We studied the effects of environmental exposure on the incidence of CNS tumors in children by subtype, according to exposure to industrial and/or urban environment, exposure to crops and according to socio-economic status of the child. METHODS: We carried out a population-based case-control study of CNS tumors in Spain, covering 714 incident cases collected from the Spanish Registry of Childhood Tumors (period 1996-2011) and 4284 controls, individually matched by year of birth, sex, and autonomous region of residence. We built a covariate to approximate the exposure to industrial and/or urban environment and a covariate for the exposure to crops (GCI) using the coordinates of the home addresses of the children. We used the 2001 Census to obtain information about socio-economic status (SES). We fitted logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (95%CIs). RESULTS: The results for all CNS tumors showed an excess risk (OR = 1.37; 95%CI = 1.09-1.73) for SES, i.e., children living in the least deprived areas had 37% more risk of CNS tumor than children living in the most deprived areas. For GCI, an increase of 10% in crop surface in the 1-km buffer around the residence implied an increase of 22% in the OR (OR = 1.22; 95%CI = 1.15-1.29). Children living in the intersection of industrial and urban areas could have a greater risk of CNS tumors than children who live outside these areas (OR = 1.20; 95%CI = 0.82-1.77). Living in urban areas (OR = 0.90; 95%CI = 0.65-1.24) or industrial areas (OR = 0.96; 95%CI = 0.81-1.77) did not seem to increase the risk for all CNS tumors together. By subtype, Astrocytomas, Intracranial and intraspinal embryonal tumors, and other gliomas showed similar results. CONCLUSION: Our results suggest that higher socioeconomic status and exposure to crops could increase the risk of CNS tumors in children.

Risk of bone tumors in children and residential proximity to industrial and urban areas: New findings from a case-control study.

Few epidemiologic studies have explored risk factors for bone tumors in children, and the role of environmental factors needs to be analyzed. Our objective was to ascertain the association between residential proximity to industrial plants and urban areas and risk of bone tumors in children, taking into account industrial groups and toxic pollutants released. A population-based case-control study of childhood bone cancer in Spain was carried out, covering 114 incident cases obtained from the Spanish Registry of Childhood Tumors (between 1996 and 2011), and 684 controls individually matched by sex, year of birth, and autonomous region of residence. Distances from the subject's residences to the 1271 industries and the 30 urban areas (towns) with ≥75,000 inhabitants located in the study area were computed. Unconditional logistic regression models were fitted to estimate odds ratios (ORs) and 95% confidence intervals (95%CIs) for categories of distance (from 1km to 3km) to industrial and urban areas, with adjustment for matching variables and sociodemographic indicators. Excess risk (OR; 95%CI) of bone tumors in children was detected for children close to industrial facilities as a whole (2.33; 1.17-4.63 at 3km) - particularly surface treatment of metals (OR=2.50; 95%CI=1.13-5.56 at 2km), production and processing of metals (OR=3.30; 95%CI=1.41-7.77 at 2.5km), urban waste-water treatment plants (OR=4.41; 95%CI=1.62-11.98 at 2km), hazardous waste (OR=4.63; 95%CI=1.37-15.61 at 2km), disposal or recycling of animal waste (OR=4.73; 95%CI=1.40-15.97 at 2km), cement and lime (OR=3.89; 95%CI=1.19-12.77 at 2.5km), and combustion installations (OR=3.85; 95%CI=1.39-10.66 at 3km)-, and urban areas (4.43; 1.80-10.92). These findings support the need for more detailed exposure assessment of certain toxics released by these facilities.

Residential proximity to environmental pollution sources and risk of rare tumors in children.

BACKGROUND: Few epidemiologic studies have explored risk factors for rare tumors in children, and the role of environmental factors needs to be assessed. OBJECTIVES: To ascertain the effect of residential proximity to both industrial and urban areas on childhood cancer risk, taking industrial groups into account. METHODS: We conducted a population-based case-control study of five childhood cancers in Spain (retinoblastoma, hepatic tumors, soft tissue sarcomas, germ cell tumors, and other epithelial neoplasms/melanomas), including 557 incident cases from the Spanish Registry of Childhood Tumors (period 1996-2011), and 3342 controls individually matched by year of birth, sex, and region of residence. Distances were computed from the residences to the 1271 industries and the 30 urban areas with ≥75,000 inhabitants located in the study area. Using logistic regression, odds ratios (ORs) and 95% confidence intervals (95%CIs) for categories of distance to industrial and urban pollution sources were calculated, with adjustment for matching variables and socioeconomic confounders. RESULTS: Children living near industrial and urban areas as a whole showed no excess risk for any of the tumors analyzed. However, isolated statistical associations (OR; 95%CI) were found between retinoblastoma and proximity to industries involved in glass and mineral fibers (2.49; 1.01-6.12 at 3km) and organic chemical industries (2.54; 1.10-5.90 at 2km). Moreover, soft tissue sarcomas registered the lower risks in the environs of industries as a whole (0.59; 0.38-0.93 at 4km). CONCLUSIONS: We have found isolated statistical associations between retinoblastoma and proximity to industries involved in glass and mineral fibers and organic chemical industries.

Agricultural crop exposure and risk of childhood cancer: new findings from a case-control study in Spain.

BACKGROUND: Childhood cancer is the main cause of disease-related death in children in Spain. Although little is known about the etiology, environmental factors are potential explanations for a fraction of the cases. Previous studies have shown pesticides to be associated with childhood cancer. The difficulty of collecting personal environmental exposure data is an important limitation; this lack of information about pesticides motivates the development of new methods to subrogate this exposure. We developed a crop exposure index based on geographic information to study the relationship between exposure to different types of crops and risk of childhood tumors. METHODS: We conducted a population-based case-control study of childhood cancer covering 3350 cases and 20,365 controls in two Spanish regions. We used CORINE Land Cover to obtain data about agricultural land use. We created a 1 km buffer around every child and calculated the percentage of crop surface within the buffer (Global Crop Index) for total crops and for individual types of crops. We fitted mixed multiple unconditional logistic regression models by diagnostic group. RESULTS: We found excess of risk among children living in the proximity of crops. For total crops our results showed excesses of risk for almost all diagnostic groups and increasing risk with increasing crop index value. Analyses by region and individual type of crop also showed excess of risk. CONCLUSION: The results suggest that living in the proximity of cultivated land could be a risk factor for several types of cancer in children.

Risk of neuroblastoma and residential proximity to industrial and urban sites: A case-control study.

BACKGROUND: Neuroblastoma is the most common extracranial solid tumor in children but its etiology is not clearly understood. While a small fraction of cases might be attributable to genetic factors, the role of environmental pollution factors needs to be assessed. OBJECTIVES: To ascertain the effect of residential proximity to both industrial and urban areas on neuroblastoma risk, taking into account industrial groups and toxic substances released. METHODS: We conducted a population-based case-control study of neuroblastoma in Spain, including 398 incident cases gathered from the Spanish Registry of Childhood Tumors (period 1996-2011), and 2388 controls individually matched by year of birth, sex, and region of residence. Distances were computed from the respective subject's residences to the 1271 industries and the 30 urban areas with ≥75,000 inhabitants located in the study area. Using logistic regression, odds ratios (ORs) and 95% confidence intervals (95%CIs) for categories of distance (from 1km to 5km) to industrial and urban pollution sources were calculated, with adjustment for matching variables and socioeconomic confounders. RESULTS: Excess risk (OR; 95%CI) of neuroblastoma was detected for the intersection between industrial and urban areas: (2.52; 1.20-5.30) for industrial distance of 1km, and (1.99; 1.17-3.37) for industrial distance of 2km. By industrial groups, excess risks were observed near 'Production of metals' (OR=2.05; 95%CI=1.16-3.64 at 1.5km), 'Surface treatment of metals' (OR=1.89; 95%CI=1.10-3.28 at 1km), 'Mines' (OR=5.82; 95%CI=1.04-32.43 at 1.5km), 'Explosives/pyrotechnics' (OR=4.04; 95%CI=1.31-12.42 at 4km), and 'Urban waste-water treatment plants' (OR=2.14; 95%CI=1.08-4.27 at 1.5km). CONCLUSIONS: These findings support the need for more detailed exposure assessment of certain substances released by these industries.

Association between residential proximity to environmental pollution sources and childhood renal tumors.

BACKGROUND: Few risk factors for childhood renal tumors are well established. While a small fraction of cases might be attributable to susceptibility genes and congenital anomalies, the role of environmental factors needs to be assessed. OBJECTIVES: To explore the possible association between residential proximity to environmental pollution sources (industrial and urban areas, and agricultural crops) and childhood renal cancer, taking into account industrial groups and toxic substances released. METHODS: We conducted a population-based case-control study of childhood renal cancer in Spain, including 213 incident cases gathered from the Spanish Registry of Childhood Tumors (period 1996-2011), and 1278 controls individually matched by year of birth, sex, and region of residence. Distances were computed from the respective subject's residences to the 1271 industries, the 30 urban areas with ≥75,000 inhabitants, and the agricultural crops located in the study area. Using logistic regression, odds ratios (ORs) and 95% confidence intervals (95%CIs) for categories of distance to pollution sources were calculated, with adjustment for matching variables and socioeconomic confounders. RESULTS: Excess risk (OR; 95%CI) of childhood renal tumors was observed for children living near (≤2.5km) industrial installations as a whole (1.97; 1.13-3.42) - particularly glass and mineral fibers (2.69; 1.19-6.08), galvanization (2.66; 1.14-6.22), hazardous waste (2.59; 1.25-5.37), ceramic (2.35; 1.06-5.21), surface treatment of metals (2.25; 1.24-4.08), organic chemical industry (2.22; 1.15-4.26), food and beverage sector (2.19; 1.18-4.07), urban and waste-water treatment plants (2.14; 1.07-4.30), and production and processing of metals (1.98; 1.03-3.82) -, and in the proximity of agricultural crops (3.16; 1.54-8.89 for children with percentage of crop surface ≥24.35% in a 1-km buffer around their residences). CONCLUSIONS: Our study provides some epidemiological evidence that living near certain industrial areas and agricultural crops may be a risk factor for childhood renal cancer.

Spatial analysis of childhood cancer: a case/control study.

BACKGROUND: Childhood cancer was the leading cause of death among children aged 1-14 years for 2012 in Spain. Leukemia has the highest incidence, followed by tumors of the central nervous system (CNS) and lymphomas (Hodgkin lymphoma, HL, and Non-Hodgkin's lymphoma, NHL). Spatial distribution of childhood cancer cases has been under concern with the aim of identifying potential risk factors. OBJECTIVE: The two objectives are to study overall spatial clustering and cluster detection of cases of the three main childhood cancer causes, looking to increase etiological knowledge. METHODS: We ran a case-control study. The cases were children aged 0 to 14 diagnosed with leukemia, lymphomas (HL and NHL) or CNS neoplasm in five Spanish regions for the period 1996-2011. As a control group, we used a sample from the Birth Registry matching every case by year of birth, autonomous region of residence and sex with six controls. We geocoded and validated the address of the cases and controls. For our two objectives we used two different methodologies. For the first, for overall spatial clustering detection, we used the differences of K functions from the spatial point patterns perspective proposed by Diggle and Chetwynd and the second, for cluster detection, we used the spatial scan statistic proposed by Kulldorff with a level for statistical significance of 0.05. RESULTS: We had 1062 cases of leukemia, 714 cases of CNS, 92 of HL and 246 of NHL. Accordingly we had 6 times the number of controls, 6372 controls for leukemia, 4284 controls for CNS, 552 controls for HL and 1476 controls for NHL. We found variations in the estimated empirical D(s) for the different regions and cancers, including some overall spatial clustering for specific regions and distances. We did not find statistically significant clusters. CONCLUSIONS: The variations in the estimated empirical D(s) for the different regions and cancers could be partially explained by the differences in the spatial distribution of the population; however, according to the literature, we cannot discard environmental hazards or infections agents in the etiology of these cancers.