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The goal of this study was to investigate the potential for selection bias in published case–control studies on household exposure to pesticides and childhood acute leukemia; most studies have reported positive findings. Items to evaluate the potential for selection bias were first developed. They focused on the source populations that gave rise to cases and controls, the probabilistic selection of subjects from the source, and the losses of the subjects actually selected. A quantitative assessment of bias was also carried out. Potential sources of selection bias were found in all the studies, but none of them were observed across all the studies. Main sources of potential bias were a non-concurrent selection of controls with respect to cases, the use of control diagnoses possibly caused by pesticide exposure in hospital-based studies, and non-participation of selected eligible subjects. A quantitative assessment of bias concluded that non-participation alone could not explain the reported positive associations. We conclude that overall, selection bias, as a likely source of bias in these studies, does not seem to explain their positive findings. Our analysis provides arguments strengthening the conclusions on associations reported in earlier studies. [ABSTRACT FROM AUTHOR]

Objective We studied the relation between Parkinson disease (PD) and professional exposure to pesticides in a community-based case-control study conducted in a population characterized by a high prevalence of exposure. Our objective was to investigate the role of specific pesticide families and to perform dose-effect analyses. Methods PD cases (n = 224) from the Mutualité Sociale Agricole (France) were matched to 557 controls free of PD affiliated with the same health insurance. Pesticide exposure was assessed using a 2-phase procedure, including a case-by-case expert evaluation. Analyses of the relation between PD and professional exposure to pesticides were first performed overall and by broad category (insecticides, fungicides, herbicides). Analyses of 29 pesticide families defined based on a chemical classification were restricted to men. Multiple imputation was used to impute missing values of pesticide families. Data were analyzed using conditional logistic regression, both using a complete-case and an imputed dataset. Results We found a positive association between PD and overall professional pesticide use (odds ratio [OR] = 1.8, 95% confidence interval [CI] = 1.1-3.1), with a dose-effect relation for the number of years of use ( p = 0.01). In men, insecticides were associated with PD (OR = 2.2, 95% CI = 1.1-4.3), in particular organochlorine insecticides (OR = 2.4, 95% CI = 1.2-5.0). These associations were stronger in men with older onset PD than in those with younger onset PD, and were characterized by a dose-effect relation in the former group. Interpretation Our results support an association between PD and professional pesticide exposure, and show that some pesticides (ie, organochlorine insecticides) may be more particularly involved. Ann Neurol 2009;66:494-504 [ABSTRACT FROM AUTHOR]

Abstract: Cancer epidemiology has undergone marked development since the 1950s. One of the most spectacular and specific contributions was the demonstration of the massive effect of smoking on the occurrence of lung, larynx, and bladder cancer. Major chemical, physical, and biological carcinogenic agents have been identified in the working environment and in the overall environment. The chain of events from environmental exposures to cancer requires hundreds of polymorphic genes coding for proteins involved in the transport and metabolism of xenobiotics, or in repair, or in an immune or inflammatory response. The multifactorial and multistage characteristics of cancer create the theoretical conditions for statistical interactions that have been exceptionally detected. Over the last two decades, a considerable mass of data has been generated, mostly addressing the interactions between smoking and xenobiotic-metabolizing enzymes in smoking-related cancers. They were sometimes considered disappointing, but they actually brought a lot of information and raised many methodological issues. In parallel, the number of polymorphisms that can be considered candidate per function increased so much that multiple testing has become a major issue, and genome wide-screening approaches have more and more gained in interest. Facing the resulting complexity, some instruments are being set up: our studies are now equipped with carefully sampled biological collections, high-throughput genotyping systems are becoming available, work on statistical methodologies is ongoing, bioinformatics databases are growing larger and access to them is becoming simpler; international consortiums are being organized. The roles of environmental and genetic factors are being jointly elucidated. The basic rules of epidemiology, which are demanding with respect to sampling, with respect to the histological and molecular criteria for cancer classification, with respect to the evaluation of environmental exposures, their timeframes, quantification and covariables, with respect to study size and with respect to the rigor of multivariate analyses, are more pertinent than ever before. To cite this article: J. Clavel, C. R. Biologies 330 (2007). [Copyright &y& Elsevier]

Using in vivo voltammetric detection of nitric oxide (NO) a previous study demonstrated an increased NO release at the lumbar dorsal horn level of the spinal cord by peripheral inflammatory processes in decerebrated-spinalized rats. This study concerns the effects of acute peripheral stimulations. Gentle non-noxious or isolated nociceptive stimulation did not modify the oxidation current due to NO. However, transient transcutaneous repetitive electrical stimulation of the hindpaw at mild to high intensities (1, 3, and 6 mA) provoked increases in the voltammograms, which were prolonged after stimulation ceased. These effects were absent in animals pretreated with the N-methyl-d-aspartate channel blocker MK-801. The data provide novel direct evidence that NO participates, at least during repetitive stimulation, in the transmission of noxious afferent messages in the dorsal horn of the spinal cord. [Copyright &y& Elsevier]

The authors offer a response to a commentary made by Catherine Hill on their study on the association between residential proximity to virticultural areas and childhood acute leukemia risk in mainland France. Topics include Hill's conclusion that the results of the study do not justify the alarming information disseminated by the media in France and strengths of the study.

Presents a study which examined the role of breast feeding and prenatal factor such as maternal history of fetal loss in the risk for childhood acute leukemia. Methodology; Analysis of results.

BACKGROUND: Pesticide exposures are suspected of being a risk factor for several childhood cancers, particularly acute leukemia (AL). Most of the evidence is based on self-reported parental domestic use of pesticides, but some studies have also addressed associations with agricultural use of pesticides near the place of residence. OBJECTIVES: The objective of the study was to evaluate the risk of AL in children living close to vines, a crop subject to intensive pesticide use. METHODS: Data were drawn from the national registry-based GEOCAP study. We included all of the AL cases under the age of 15 years diagnosed in 2006–2013 (푛 = 3,711) and 40,196 contemporary controls representative of the childhood population in France. The proximity of the vines (probability of presence within 200, 500, and 1,000 m) and the viticulture density (area devoted to vines within 1,000 m) were evaluated around the geocoded addresses in a geographic information system combining three national land use maps. Logistic regression models were used to estimate odds ratios (ORs) for all AL and for the lymphoblastic (ALL) and myeloid (AML) subtypes. Heterogeneity between regions was studied by stratified analyses. Sensitivity analyses were carried out to take into account, in particular, geocoding uncertainty, density of other crops and potential demographic and environmental confounders. RESULTS: In all, about 10% of the controls lived within 1 km of vines. While no evidence of association between proximity to vines and AL was found, viticulture density was positively associated with ALL [OR=1.05 (1.00–1.09) for a 10% increase in density], with a statistically significant heterogeneity across regions. No association with AML was observed. The results remained stable in all the sensitivity analyses. CONCLUSION: We evidenced a slight increase in the risk of ALL in children living in areas with high viticulture density. This finding supports the hypothesis that environmental exposure to pesticides may be associated with childhood ALL. [ABSTRACT FROM AUTHOR]

Few studies have investigated the seasonal patterns of embryonal tumours. Based on data from the French National Registry of Childhood Cancers, the present study aimed to investigate seasonal variations in embryonal tumour incidence rates by month of birth and by month of diagnosis. The study included 6635 primary embryonal tumour cases diagnosed before the age of 15 years over the period 2000‐2015 in mainland France. Assuming monthly variations in incidence rates were homogeneous over 2000‐2015, we used a Poisson regression model to test for overall heterogeneity in standardised incidence ratios (SIRs) by month of birth or diagnosis. The seasonal scan statistic method was used to detect monthly excesses or deficits of embryonal tumour cases over the whole study period. The annual reproducibility of the observed monthly variations was formally tested. An overall heterogeneity in incidence rates by month of birth was observed for rhabdomyosarcoma in boys only. Based on the month of diagnosis, a seasonality was evidenced for unilateral retinoblastoma, with a lower incidence rate in the summer (SIRJul‐Aug = 0.68, 95% CI = 0.52‐0.87), whilst the incidence rate of rhabdomyosarcoma tended to be lower in August (SIRAug = 0.68, 95% CI = 0.52‐0.89). No seasonality was detected for the other embryonal tumour groups by month of birth or month of diagnosis. This study is one of the largest to have investigated the seasonality of childhood embryonal tumours. The study showed a seasonal variation in the incidence rates by month of diagnosis for unilateral retinoblastoma and rhabdomyosarcoma. Our findings are likely to reflect a delay in consultation during the summer months. However, the role of seasonally varying environmental exposures cannot be ruled out. [ABSTRACT FROM AUTHOR]

Background: Domestic and parental occupational pesticide exposures are suspected of involvement in the occurrence of childhood acute leukaemia (AL), but the role of exposure to agricultural activities is little known. In a previous ecological study conducted in France, we observed an increase in acute lymphoblastic leukaemia (ALL) incidence rate with increasing viticulture density in the municipalities of residence at diagnosis.Objectives: This study aimed to test the hypothesis that residential proximity to croplands at birth increases the risk of childhood AL, with a particular focus on vineyards.Methods: We identified all the primary AL cases diagnosed before the age of 15 years in the cohorts of children born in the French municipalities between 1990 and 2015. We estimated crop densities in each municipality of residence at birth using agricultural census data, for ten crop types. Variations in standardized incidence ratios (SIR) were evaluated with Poisson regression models, for all AL, ALL and acute myeloid leukaemia (AML), separately.Results: Among the 19,809,700 children born and residing in mainland France at birth in 1990-2015, 8,747 AL cases (7,236 ALL and 1,335 AML) were diagnosed over the period. We did not evidence any statistically significant positive association between total crop density or any specific crop density in the municipality of residence at birth and all AL, ALL or AML. Interestingly, we observed a higher ALL incidence rate in the municipalities with the highest viticulture densities (SIR = 1.25 95%CI [1.01-1.54]). Adjusting for the main potential confounders did not change the results.Conclusion: Our study does not support the hypothesis that residential proximity to croplands, particularly vineyards, around birth plays a role in childhood leukaemia. The slightly higher ALL incidence rate in children born in the municipalities with the highest viticulture densities may reflect the previously-observed association at diagnosis. [ABSTRACT FROM AUTHOR]

Purpose: During the COVID-19 pandemic, childhood cancer survivors (CCS) may have felt more at risk of having severe consequences of COVID-19 and therefore may have been more likely to defer their health care use. We aimed to assess the risk perceptions of CCS related to COVID-19 (perceived infection risk, perceived risk of experiencing a severe illness in the event of infection), and their forgoing of health care during the year 2020.Methods: In December 2020, we interviewed through an online self-report questionnaire 580 5-year CCS participating in the French Childhood Cancer Survivor Study (FCCSS) cohort. Combining clinical and patient-reported outcomes, we studied predictors of perceived risks related to COVID-19 and forgoing health care.Results: Overall, 60% of respondents stated that COVID-19 could have severe consequences for their health if infected. Survivors with a cardiovascular disease and those who felt more at risk of being infected were more likely to think that COVID-19 could have severe health consequences for them. Moreover, 30% of respondents seeking care declared they had forgone at least one medical appointment in 2020. Forgoing medical appointments was more common among CCS who reported a deterioration in their financial situation in 2020 and those who felt more at risk of being infected.Conclusions: This study shows that a considerable proportion of survivors had forgone medical appointments because of the pandemic; forgoing care was more frequent among the most socioeconomically disadvantaged survivors.Implications For Cancer Survivors: This study presents data hitherto absent in the literature and suggests the need to develop telehealth to ensure appropriate long-term follow-up of CCS. [ABSTRACT FROM AUTHOR]

Background: Compared with the general population, childhood cancer survivors (CCS) could be at greater risk of psychological distress following the emergence of the COVID-19 pandemic. Purpose: This cross-sectional study assessed the psychological consequences of COVID-19 on the mental health of CCS. Design and participants: In December 2020, we interviewed through an online self-report questionnaire, 580 5-year CCS participating in the French Childhood Cancer Survivor Study (FCCSS) cohort. Methods: We first compared the mental health score of CCS with that observed in the French general population of the same age and gender. Subsequently, we studied predictors of the mental health score of CCS. Results: External comparisons revealed that the mental health score of CCS was similar to that of the general population. Among CCS, almost 42% stated that their psychological state had been worse during the lockdown. Predictors of poorer mental health included, among others, female gender, reporting a change in the occupational situation, having a relative who had been hospitalized or had died following COVID-19, and a greater perceived infection risk. Interpretation and Implications: Given the pre-existing vulnerability of some CCS to mental distress, the additional psychological consequences of COVID-19 in vulnerable survivors should receive attention from health care providers. [ABSTRACT FROM AUTHOR]

Background: Acute leukemia is the most common cancer in children under 15 years of age; 80% are acute lymphoblastic leukemia (ALL) and 17% are acute myeloid leukemia (AML). Childhood leukemia shows further diversity based on cytogenetic and molecular characteristics, which may relate to distinct etiologies. Case--control studies conducted worldwide, particularly of ALL, have collected a wealth of data on potential risk factors and in some studies, biospecimens. There is growing evidence for the role of infectious/immunologic factors, fetal growth, and several environmental factors in the etiology of childhood ALL. The risk of childhood leukemia, like other complex diseases, is likely to be influenced both by independent and interactive effects of genes and environmental exposures. While some studies have analyzed the role of genetic variants, few have been sufficiently powered to investigate gene--environment interactions. Objectives: The Childhood Leukemia International Consortium (CLIC) was established in 2007 to promote investigations of rarer exposures, gene--environment interactions and subtype-specific associations through the pooling of data from independent studies. Methods: By September 2012, CLIC included 22 studies (recruitment period: 1962--present) from 12 countries, totaling approximately 31 000 cases and 50 000 controls. Of these, 19 case--control studies have collected detailed epidemiologic data, and DNA samples have been collected from children and child--parent trios in 15 and 13 of these studies, respectively. Two registry-based studies and one study comprising hospital records routinely obtained at birth and/or diagnosis have limited interview data or biospecimens. Conclusions: CLIC provides a unique opportunity to fill gaps in knowledge about the role of environmental and genetic risk factors, critical windows of exposure, the effects of gene--environment interactions and associations among specific leukemia subtypes in different ethnic groups. [ABSTRACT FROM AUTHOR]

Epidemiological studies have been consistent in showing that cigarette smoking is inversely associated with Parkinson's disease (PD), whereas pesticide use is positively associated with PD. However, the relationship between PD and cigarette smoking remains poorly understood. Our objective was to study the relationship between cigarette smoking and PD in a population characterized by a high prevalence of pesticide exposure. This case-control study was carried out among subjects enrolled in the Mutualité Sociale Agricole, the French health insurance organization for workers connected to the agricultural world. We included 247 cases and 676 controls matched on age, sex, and region of residency. Information on smoking was obtained through in-person interviews. Pesticide exposure was assessed using a case-by-case expert evaluation procedure. We found an inverse relationship between ever cigarette smoking and PD (odds ratio [OR] = 0.6; 95% confidence interval [CI] = 0.4-0.9). The strength of this association increased with the number of pack-years. This relationship was present even when smoking was considered as long as 40 years before PD onset. An inverse association was also present among subjects professionally exposed to pesticides (OR = 0.5; 95% CI = 0.3-0.8) and was independent of the duration of exposure among men. We confirm the inverse association between cigarette smoking and PD in a population characterized by a high prevalence of professional pesticide exposure. The relationship between PD and cigarette smoking was not significantly modified or confounded by exposure to pesticides. © 2004 Movement Disorder Society [ABSTRACT FROM AUTHOR]

Exposure to pesticides has been suggested as a potential risk factor for childhood embryonal tumour. The existing literature has mainly focused on parental occupational exposure and domestic use of pesticides, and is very limited for residential exposures to agricultural pesticides. The study aimed to test the hypothesis of an increased risk of embryonal tumour in children living close to viticultural plots, likely to be subject to frequent pesticide applications. The study is part of the French national registry-based GEOCAP program. We included 2761 cases of neuroblastoma, retinoblastoma, Wilms tumour and rhabdomyosarcoma diagnosed before the age of 15 years in the 2006–2013 period, and 40,196 controls representative of the same age population during this period. Indicators of proximity to vines, the presence of vines and viticulture density within 1000 m of the geocoded addresses of residence, were evaluated combining three sources of data on agricultural land use in a geographic information system. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regressions and carried out several sensitivity analyses to test the stability of the results. Approximately 10% of the controls lived within 1000 m of vines, with regional variations ranging from <1% to 38%. We observed a 5% increase in the risk of neuroblastoma for a 10% increase in viticulture density (OR = 1.05, 95% CI: 0.98–1.13), with a regional heterogeneity. The indicators of proximity to vines were not associated with the other non-CNS embryonal tumours. The study showed a slight increase in the risk of neuroblastoma in children living close to vines, suggesting that residential exposure to agricultural pesticides may be involved in the occurrence of these tumours. • National study with 2761 embryonal tumour cases and 40,196 population controls. • Residential proximity to vines was assessed using nationwide crop maps. • Neuroblastoma risk increased by 5% for a 10% increase in density of vines < 1 km. • There was no association with the other embryonal tumours under study. [ABSTRACT FROM AUTHOR]

Evidence for an association of foetal growth with acute myeloid leukaemia (AML) is inconclusive. AML is a rare childhood cancer, relatively more frequent in girls, with distinct features in infancy. In the context of the Childhood Leukemia International Consortium (CLIC), we examined the hypothesis that the association may vary by age, sex and disease subtype using data from 22 studies and a total of 3564 AML cases. Pooled estimates by age, sex and overall for harmonised foetal growth markers in association with AML were calculated using the International Fetal and Newborn Growth Consortium for the 21st Century Project for 17 studies contributing individual-level data; meta-analyses were, thereafter, conducted with estimates provided ad hoc by five more studies because of administrative constraints. Subanalyses by AML subtype were also performed. A nearly 50% increased risk was observed among large-for-gestational-age infant boys (odds ratio [OR]: 1.49, 95% confidence interval [CI]: 1.03–2.14), reduced to 34% in boys aged <2 years (OR: 1.34, 95% CI: 1.05–1.71) and 25% in boys aged 0–14 years (OR: 1.25, 95% CI: 1.06–1.46). The association of large for gestational age became stronger in boys with M0/M1subtype (OR: 1.80, 95% CI: 1.15–2.83). Large birth length for gestational age was also positively associated with AML (OR: 1.38, 95% CI: 1.00–1.92) in boys. By contrast, there were null associations in girls, as well as with respect to associations of decelerated foetal growth markers. Accelerated foetal growth was associated with AML, especially in infant boys and those with minimally differentiated leukaemia. Further cytogenetic research would shed light into the underlying mechanisms. • Accelerated foetal growth was associated with childhood acute myeloid leukaemia. • The association was marked in large-for-gestational-age newborns. • The association was stronger in infant boys and minimally differentiated leukaemia. • Accelerated foetal growth age-, sex- and subtype- related differentials were showed. • These associations could shed light into the biology of AML and its subtypes. [ABSTRACT FROM AUTHOR]

Background: Small bowel cancer is not a single entity. Population-based studies taking into account histological diversity are scarce. The aim of this study was to report on their trends in incidence by histology in France over the past 20 years.Methods: All patients with a small bowel cancer diagnosed in 15 French administrative areas covered by a registry from the network of French cancer registries (FRANCIM) were included. Age-standardized incidence rates were estimated using the world standard population. Incidence rates were calculated by gender, age group, histology, and 5-year period.Results: The overall age-standardized incidence rates were 1.46/100,000 inhabitants in men and 0.9/100,000 inhabitants in women. Adenocarcinoma was the most common histological type (38%), followed by neuroendocrine tumors (35%), lymphoma (15%) and sarcoma (12%). Age at diagnosis and tumor location differed between adenocarcinoma and neuroendocrine tumors. The incidence of all four tumor types increased significantly over the 20-year period, with the exception of lymphoma in men. The annual percentage change for neuroendocrine tumors was 3.89% in men and 3.61% in women; for sarcoma, it was 3.38% and 4.08%, respectively. The incidence of adenocarcinoma and lymphoma also increased in women with an annual percentage change of 3.05% and 3.32%, respectively.Conclusion: Small bowel cancer incidence has increased over time. This increase occurred with different amplitudes and patterns in the four major histological types. The improvement in imaging techniques could partly explain this increase. It is necessary to determine whether predisposing conditions may contribute to this change. [ABSTRACT FROM AUTHOR]

Background: Childhood cancer is a rare but leading cause of morbidity and mortality. Established risk factors, accounting for <10% of incidence, have been identified primarily from case-control studies. However, recall, selection and other potential biases impact interpretations particularly, for modest associations. A consortium of pregnancy and birth cohorts (I4C) was established to utilise prospective, pre-diagnostic exposure assessments and biological samples.Methods: Eligibility criteria, follow-up methods and identification of paediatric cancer cases are described for cohorts currently participating or planning future participation. Also described are exposure assessments, harmonisation methods, biological samples potentially available for I4C research, the role of the I4C data and biospecimen coordinating centres and statistical approaches used in the pooled analyses.Results: Currently, six cohorts recruited over six decades (1950s-2000s) contribute data on 388 120 mother-child pairs. Nine new cohorts from seven countries are anticipated to contribute data on 627 500 additional projected mother-child pairs within 5 years. Harmonised data currently includes over 20 "core" variables, with notable variability in mother/child characteristics within and across cohorts, reflecting in part, secular changes in pregnancy and birth characteristics over the decades.Conclusions: The I4C is the first cohort consortium to have published findings on paediatric cancer using harmonised variables across six pregnancy/birth cohorts. Projected increases in sample size, expanding sources of exposure data (eg, linkages to environmental and administrative databases), incorporation of biological measures to clarify exposures and underlying molecular mechanisms and forthcoming joint efforts to complement case-control studies offer the potential for breakthroughs in paediatric cancer aetiologic research. [ABSTRACT FROM AUTHOR]

Background: Significant increases in childhood cancer incidence since the 1970s have been consistently reported worldwide, but the persistence of the increase on recent periods is discussed. No conclusion can be drawn concerning the spatial variations of childhood cancer, either. This study is an in‐depth investigation of the spatial and temporal variations of childhood cancer in France. An extensive review of all the studies published since 2000 on those issues is provided. Methods: The study included 25 877 cases of childhood cancer registered nationwide over 2000‐2014. The spatial heterogeneity (overdispersion, autocorrelation, overall heterogeneity) was tested, on two geographic scales, and two spatial scan methods were used to detect clusters of cases. The annual average percent change (AAPC) in incidence rate was estimated with Poisson regression models, and joinpoint analyses were considered. Results: Glioma and non‐Hodgkin lymphoma cases exhibited some spatial heterogeneity and two large clusters were detected. Overall, the incidence rate of childhood cancer was stable over 2000‐2014 (AAPC = −0.1% [−0.3%; 0.2%]). A log‐linear positive trend was significantly evidenced for gliomas other than pilocytic astrocytomas (AAPC = 1.8% [0.9%; 2.7%]), with some suggestion of a leveling‐off at the end of the period, while Burkitt lymphoma and germ cell tumor incidence rates decreased (AAPC = −2.2% [−3.8%; −0.5%] and AAPC = −1.9% [−3.4%; −0.3%], respectively). No spatial heterogeneity or significant time variation was evidenced for other cancers. Conclusion: Several types of childhood cancer displayed some spatial heterogeneity and two large clusters were detected, the origins of which are to be investigated and might include differences in case ascertainment. Overall, the results do not support a sustained increase in incidence rates of childhood cancer in recent years. With 25 877 cases registered nationwide over 15 years, this study provides substantial information on the spatial and temporal variations of childhood cancer. A review of recent published papers on spatial and temporal variations of childhood cancer is also provided. Several complementary methods were used to highlight main spatial and temporal trends in the incidence rate of all childhood cancers in France. Several types of childhood cancer displayed some spatial heterogeneity, and two large unexplained clusters were detected. Spatial differences in case ascertainment cannot be ruled out. Overall, the results do not support a sustained increase in incidence rates of childhood cancer in recent years. [ABSTRACT FROM AUTHOR]

Background: Although studies have consistently found an association between childhood leukaemia risk and magnetic fields, the associations between childhood leukaemia and distance to overhead power lines have been inconsistent. We pooled data from multiple studies to assess the association with distance and evaluate whether it is due to magnetic fields or other factors associated with distance from lines.Methods: We present a pooled analysis combining individual-level data (29,049 cases and 68,231 controls) from 11 record-based studies.Results: There was no material association between childhood leukaemia and distance to nearest overhead power line of any voltage. Among children living < 50 m from 200 + kV power lines, the adjusted odds ratio for childhood leukaemia was 1.33 (95% CI: 0.92-1.93). The odds ratio was higher among children diagnosed before age 5 years. There was no association with calculated magnetic fields. Odds ratios remained unchanged with adjustment for potential confounders.Conclusions: In this first comprehensive pooled analysis of childhood leukaemia and distance to power lines, we found a small and imprecise risk for residences < 50 m of 200 + kV lines that was not explained by high magnetic fields. Reasons for the increased risk, found in this and many other studies, remains to be elucidated. [ABSTRACT FROM AUTHOR]

Abstract: The associations between childhood acute lymphoblastic leukemia (ALL) and several factors related to early stimulation of the immune system, that is, farm residence and regular contacts with farm animals (livestock, poultry) or pets in early childhood, were investigated using data from 13 case–control studies participating in the Childhood Leukemia International Consortium. The sample included 7847 ALL cases and 11,667 controls aged 1–14 years. In all studies, the data were obtained from case and control parents using standardized questionnaires. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by unconditional logistic regression adjusted for age, sex, study, maternal education, and maternal age. Contact with livestock in the first year of life was inversely associated with ALL (OR = 0.65, 95% CI: 0.50, 0.85). Inverse associations were also observed for contact with dogs (OR = 0.92, 95% CI: 0.86, 0.99) and cats (OR = 0.87, 95% CI: 0.80, 0.94) in the first year of life. There was no evidence of a significant association with farm residence in the first year of life. The findings of these large pooled and meta‐analyses add additional evidence to the hypothesis that regular contact with animals in early childhood is inversely associated with childhood ALL occurrence which is consistent with Greaves’ delayed infection hypothesis. [ABSTRACT FROM AUTHOR]

BACKGROUND: Exposures to high-dose ionizing radiation and high-dose rate ionizing radiation are established risk factors for childhood acute leukemia (AL). The risk of AL following exposure to lower doses due to natural background radiation (NBR) has yet to be conclusively determined. METHODS: AL cases diagnosed over 1990-2009 (9,056 cases) were identified and their municipality of residence at diagnosis collected by the National Registry of Childhood Cancers. The Geocap study, which included the 2,763 cases in 2002-2007 and 30,000 population controls, was used for complementary analyses. NBR exposures were modeled on a fine scale (36,326 municipalities) based on measurement campaigns and geological data. The power to detect an association between AL and dose to the red bone marrow (RBM) fitting UNSCEAR (United Nations Scientific Committee on the Effects of Atomic Radiation) predictions was 92%, 45% and 99% for exposure to natural gamma radiation, radon and total radiation, respectively. RESULTS: AL risk, irrespective of subtype and age group, was not associated with the exposure of municipalities to radon or gamma radiation in terms of yearly exposure at age reached, cumulative exposure or RBM dose. There was no confounding effect of census-based socio-demographic indicators, or environmental factors (road traffic, high voltage power lines, vicinity of nuclear plants) related to AL in the Geocap study. CONCLUSIONS: Our findings do not support the hypothesis that residential exposure to NBR increases the risk of AL, despite the large size of the study, fine scale exposure estimates and wide range of exposures over France. However, our results at the time of diagnosis do not rule out a slight association with gamma radiation at the time of birth, which would be more in line with the recent findings in the UK and Switzerland. CITATION: Demoury C, Marquant F, Ielsch G, Goujon S, Debayle C, Faure L, Coste A, Laurent O, Guillevic J, Laurier D, Hémon D, Clavel J. 2017. Residential exposure to natural background radiation and risk of childhood acute leukemia in France, 1990-2009. Environ Health Perspect 125:714-720; http://dx.doi.org/10.1289/EHP296 [ABSTRACT FROM AUTHOR]

Background: Socio-economic status is related to many life style and environmental factors, some of which have been suggested to influence the risk of childhood cancer. Studies requiring subject participation are usually hampered by selection of more educated parents. To prevent such bias, we used unselected nationwide Geographical Information System (GIS)-based registry data, to investigate the influence of socio-economic disparities on the risk of childhood cancer.Methods: The Geocap study included all French residents diagnosed with cancer aged up to 15 years over the period 2002-2010 (15 111 cases) and 45 000 contemporaneous controls representative of the childhood population. Area socio-economic characteristics used to calculate the European Deprivation Index (EDI) were based on census data collected on the fine scale of the Merged Islet for Statistical Information (IRIS).Results: Overall, the risk of acute lymphoblastic leukaemia (ALL) was lower in the most deprived quintile than in the other quintiles of EDI (ORQ5vsConclusion: Living in the most deprived areas was inversely associated with the risk of ALL in childhood. There was no indication that the risk of childhood cancer of any site could be increased by deprivation. Life style or environmental factors potentially underlying the association need further investigation. [ABSTRACT FROM AUTHOR]

Family clusters of multiple myeloma ( MM) suggest disease heritability. Nevertheless, patterns of inheritance and the importance of genetic versus environmental risk factors in MM aetiology remain unclear. We pooled data from eleven case-control studies from the International Multiple Myeloma Consortium to characterize the association of MM risk with having a first-degree relative with a history of a lympho-haematapoietic cancer. Unconditional logistic regression models, adjusted for study, sex, age and education level, were used to estimate associations between MM risk and having a first-degree relative with a history of non-Hodgkin lymphoma, Hodgkin lymphoma, leukaemia or MM. Sex, African American race/ethnicity and age were explored as effect modifiers. A total of 2843 cases and 11 470 controls were included. MM risk was elevated in association with having a first-degree relative with any lympho-haematapoietic cancer (Odds Ratio (OR) = 1·29, 95% Confidence Interval (CI): 1·08-1·55). The association was particularly strong for having a first-degree relative with MM (OR = 1·90, 95% CI: 1·26-2·87), especially among men (OR = 4·13, 95% CI: 2·17-7·85) and African Americans (OR = 5·52, 95% CI: 1·87-16·27).These results support the hypothesis that genetic inheritance plays a role in MM aetiology. Future studies are warranted to characterize interactions of genetic markers with environmental exposures. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to assess the risk of childhood central nervous system (CNS) tumors associated with parental occupational pesticide exposure. Methods: We pooled three population-based case-control studies from France, Germany, and the United Kingdom. Cases were children below 15 years of age with CNS tumors; controls were matched by gender and age. A general population job-exposure matrix assessed parental occupational pesticide exposure. Logistic regressions estimated odds ratios (ORs) and 95% confidence intervals (CIs). Results: The study included 1361 cases and 5498 controls. Prevalence of maternal occupational pesticide exposure during pregnancy was low and no association with childhood CNS tumors was detected (OR 0.76, 95% Cl: 0.41 to 1.41). Around conception, OR for childhood CNS tumors associated with paternal occupational pesticide exposure was 0.71 (95% Cl: 0.53 to 0.95). Conclusion: Our results do not suggest a role of parental occupational pesticide exposure in the etiology of childhood CNS tumors. [ABSTRACT FROM AUTHOR]

Parental occupational exposures around conception (father) or during pregnancy (mother) have been hypothesized as potential predisposing factors for childhood leukaemia. We investigated parental exposure to several known occupational carcinogens and childhood leukaemia risk. We conducted a pooled analysis using case-control data from four European countries (3362 childhood leukemia cases and 6268 controls). Parental occupational exposures to polycyclic aromatic hydrocarbons (PAH), diesel engine exhaust (DEE), chromium, nickel, crystalline silica, and asbestos were assessed by a general population job-exposure matrix. We estimated odd ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression models for all childhood leukaemia combined, by leukaemia type (ALL and AML) and by ALL subtype (B-lineage and T-lineage). We found an association between high paternal occupational exposure to crystalline silica and childhood ALL (OR 2.20, CI 1.60–3.01) with increasing trend from no exposure to high exposure (P = <0.001), and also for AML (OR 2.03, CI 1.04–3.97; P for trend = 0.008). ORs were similar for B- and T-lineage ALL. For ALL, ORs were also slightly elevated with wide confidence intervals for high paternal occupational exposure to chromium (OR 1.23, CI 0.77–1.96), and DEE (OR 1.21, CI 0.82–1.77). No associations were observed for paternal exposures to nickel, PAH and asbestos. For maternal occupational exposure we found several slightly elevated odds ratios but mostly with very wide confidence intervals due to low numbers of exposed mothers. This is a first study suggesting an association between fathers' occupational exposure to crystalline silica and an increased risk of childhood leukaemia in their offspring. As this association was driven by certain occupations (field crop farmers and miners) where other potentially relevant exposures like pesticides and radon may also occur, more research is needed to confirm our findings of an association with crystalline silica, and if so, mechanistic studies to understand the pathways. [ABSTRACT FROM AUTHOR]

BACKGROUND: Various occupations have been associated with an elevated risk of non-Hodgkin lymphoma (NHL), but results have been inconsistent across studies. Objectives: We investigated occupational risk of NHL and of four common NHL subtypes with particular focus on occupations of a priori interest. METHODS: We conducted a pooled analysis of 10,046 cases and 12,025 controls from 10 NHL studies participating in the InterLymph Consortium. We harmonized the occupational coding using the 1968 International Standard Classification of Occupations (ISCO-1968) and grouped occupations previously associated with NHL into 25 a priori groups. Odds ratios (ORs) adjusted for center, age, and sex were determined for NHL overall and for the following four subtypes: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), chronic lymphocytic leukemia/ small lymphocytic lymphoma (CLL/SLL), and peripheral T-cell lymphoma (PTCL). RESULTS: We confirmed previously reported positive associations between NHL and farming occupations [field crop/vegetable farm workers OR = 1.26; 95% confidence interval (CI): 1.05, 1.51; general farm workers OR = 1.19; 95% CI: 1.03, 1.37]; we also confirmed associations of NHL with specific occupations such as women's hairdressers (OR = 1.34; 95% CI: 1.02, 1.74), charworkers/cleaners (OR = 1.17; 95% CI: 1.01, 1.36), spray-painters (OR = 2.07; 95% CI: 1.30, 3.29), electrical wiremen (OR = 1.24; 95% CI: 1.00, 1.54), and carpenters (OR = 1.42; 95% CI: 1.04, 1.93). We observed subtype-specific associations for DLBCL and CLL/SLL in women's hairdressers and for DLBCL and PTCL in textile workers. CONCLUSIONS: Our pooled analysis of 10 international studies adds to evidence suggesting that farming, hairdressing, and textile industry-related exposures may contribute to NHL risk. Associations with women's hairdresser and textile occupations may be specific for certain NHL subtypes. [ABSTRACT FROM AUTHOR]

Noonan syndrome is associated with a range of malignancies including acute lymphoblastic leukemia (ALL). However, little information is available regarding the frequency, natural history, characteristics and prognosis of ALL in Noonan syndrome or RASopathies in general. Cross-referencing data from a large prospective cohort of 1176 patients having a molecularly confirmed RASopathy with data from the French childhood cancer registry allowed us to identify ALL in 6 (0.5%) patients including 4/778 (0.5%) with a germline PTPN11 mutation and 2/94 (2.1%) with a germline SOS1 mutation. None of the patients of our series with CFC syndrome (with germline BRAF or MAP2K1 / MAP2K2 mutation – n = 121) or Costello syndrome (with HRAS mutation – n = 35) had an ALL. A total of 19 Noonan-ALL were gathered by adding our patients to those of the International Berlin-Munster-Frankfurt (I-BFM) study group and previously reported patients. Strikingly, all Noonan-associated ALL were B-cell precursor ALL, and high hyperdiploidy with more than 50 chromosomes was found in the leukemia cells of 13/17 (76%) patients with available genetics data. Our data suggest that children with Noonan syndrome are at higher risk to develop ALL. Like what is observed for somatic PTPN11 mutations, NS is preferentially associated with the development of hyperdiploid ALL that will usually respond well to chemotherapy. However, Noonan syndrome patients seem to have a propensity to develop post therapy myelodysplasia that can eventually be fatal. Hence, one should be particularly cautious when treating these patients. [ABSTRACT FROM AUTHOR]

Childhood leukemia may be associated with traffic-related environmental exposure to benzene, and additional data are needed. The Géolocalisation des Cancers Pédiatriques (GEOCAP) Study, a nationwide French case-control study, was designed to avoid selection bias due to differential participation and misclassification. The study compared the 2,760 childhood leukemia cases diagnosed in France between 2002 and 2007 (including 2,275 cases of acute lymphoblastic leukemia (ALL) and 418 cases of acute myeloblastic leukemia (AML)) with 30,000 contemporaneous child population controls. The residence addresses were precisely geocoded, and 3 indicators of residential proximity to traffic were considered. Estimates of benzene concentrations were also available for the Île-de-France region (including Paris). A 300-m increase in major road length within 150 m of the geocoded address was significantly associated with AML (odds ratio = 1.2, 95%confidence interval: 1.0, 1.4) but not with ALL (odds ratio = 1.0, 95% confidence interval: 0.9, 1.1), and the association was reinforced in the Île-de-France region when this indicator was combined with benzene estimates. These results, which were free from any participation bias and based on objectively determined indices of exposure, showed an increased incidence of AML associated with heavy-traffic road density near a child's home. The results support a role for traffic-related benzene exposure in the etiology of childhood AML. [ABSTRACT FROM AUTHOR]

The associations between childhood acute lymphoblastic leukemia (ALL) and several proxies of early stimulation of the immune system, that is, day-care center attendance, birth order, maternally reported common infections in infancy, and breastfeeding, were investigated by using data from 11 case-control studies participating in the Childhood Leukemia International Consortium (enrollment period: 1980-2010). The sample included 7,399 ALL cases and 11,181 controls aged 2-14 years. The data were collected by questionnaires administered to the parents. Pooled odds ratios and 95% confidence intervals were estimated by unconditional logistic regression adjusted for age, sex, study, maternal education, and maternal age. Day-care center attendance in the first year of life was associated with a reduced risk of ALL (odds ratio = 0.77, 95% confidence interval: 0.71, 0.84), with a marked inverse trend with earlier age at start (P < 0.0001). An inverse association was also observed with breastfeeding duration of 6 months or more (odds ratio = 0.86, 95% confidence interval: 0.79, 0.94). No significant relationship with a history of common infections in infancy was observed even though the odds ratio was less than 1 for more than 3 infections. The findings of this large pooled analysis reinforce the hypothesis that day-care center attendance in infancy and prolonged breastfeeding are associated with a decreased risk of ALL. [ABSTRACT FROM AUTHOR]

Genome-wide association studies (GWAS) have identified that frequent polymorphisms in ARID5B and IKZF1, two genes involved in lymphoid differentiation, increase the risk of childhood acute lymphoblastic leukemia (ALL). These findings markedly modified the current field of research on the etiology of ALL. In this new context, the present exploratory study investigated the possible interactions between these at-risk alleles and the non-genetic suspected ALL risk factors that were of sufficient prevalence in the French ESCALE study: maternal use of home insecticides during pregnancy, preconception paternal smoking, and some proxies for early immune modulation, i.e. breastfeeding, history of common infections before age one year, and birth order. The analyses were based on 434 ALL cases and 442 controls of European origin, drawn from the nationwide population-based case-control study ESCALE. Information on non-genetic factors was obtained by standardized telephone interview. Interactions between rs10740055 in ARID5B or rs4132601 in IKZF1 and each of the suspected non-genetic factors were tested, with the SNPs coded as counts of minor alleles (trend variable). Statistical interactions were observed between rs4132601 and maternal insecticide use (p = 0.012), breastfeeding p = 0.017) and repeated early common infections (p = 0.0070), with allelic odds ratios (OR) which were only increased among the children not exposed to insecticides (OR = 1.8, 95%CI: 1.3, 2.4), those who had been breastfed (OR = 1.8, 95%CI: 1.3, 2.5) and those who had had repeated early common infections (OR = 2.4, 95%CI: 1.5, 3.8). The allelic ORs were close to one among children exposed to insecticides, who had not been breastfed and who had had no or few common infections. Repeated early common infections interacted with rs10740055 (p = 0.018) in the case-only design. Further studies are needed to evaluate whether these observations of a modification of the effect of the at-risk alleles by non-genetic factors are chance findings or reflect true underlying mechanisms. [ABSTRACT FROM AUTHOR]

Genome wide association studies (GWAS) have established association of ARID5B and IKZF1 variants with childhood acute lymphoblastic leukemia (ALL). Epidemiological studies suggest that environmental factors alone appear to make a relatively minor contribution to disease risk. The polygenic nature of childhood ALL predisposition together with the timing of environmental triggers may hold vital clues for disease etiology. This study presents results from an Australian GWAS of childhood ALL cases (n = 358) and population controls (n = 1192). Furthermore, we utilised family trio (n = 204) genotypes to extend our investigation to gene-environment interaction of significant loci with parental exposures before conception, and child’s sex and age. Thirteen SNPs achieved genome wide significance in the population based case/control analysis; ten annotated to ARID5B and three to IKZF1. The most significant SNPs in these regions were ARID5B rs4245595 (OR 1.63, CI 1.38–1.93, P = 2.13×10−9), and IKZF1 rs1110701 (OR 1.69, CI 1.42–2.02, p = 7.26×10−9). There was evidence of gene-environment interaction for risk genotype at IKZF1, whereby an apparently stronger genetic effect was observed if the mother took folic acid or if the father did not smoke prior to pregnancy (respective interaction P-values: 0.04, 0.05). There were no interactions of risk genotypes with age or sex (P-values >0.2). Our results evidence that interaction of genetic variants and environmental exposures may further alter risk of childhood ALL however, investigation in a larger population is required. If interaction of folic acid supplementation and IKZF1 variants holds, it may be useful to quantify folate levels prior to initiating use of folic acid supplements. [ABSTRACT FROM AUTHOR]

The article discusses the impact of treatment on children with down syndrome associated acute lymphoblastic leukaemia and reduction drug doses. Topics discussed include toxicity caused corticosteroid therapy, especially dexamethasone to regulate immune suppression, white blood cell count or immunophenotype.

Summary: Background: Survival and cure rates for childhood cancers in Europe have greatly improved over the past 40 years and are mostly good, although not in all European countries. The EUROCARE-5 survival study estimates survival of children diagnosed with cancer between 2000 and 2007, assesses whether survival differences among European countries have changed, and investigates changes from 1999 to 2007. Methods: We analysed survival data for 157 499 children (age 0–14 years) diagnosed between Jan 1, 1978 and Dec 31, 2007. They came from 74 population-based cancer registries in 29 countries. We calculated observed, country-weighted 1-year, 3-year, and 5-year survival for major cancers and all cancers combined. For comparison between countries, we used the corrected group prognosis method to provide survival probabilities adjusted for multiple confounders (sex, age, period of diagnosis, and, for all cancers combined without CNS cancers, casemix). Age-adjusted survival differences by area and calendar period were calculated with period analysis and were given for all cancers combined and the major cancers. Findings: We analysed 59 579 cases. For all cancers combined for children diagnosed in 2000–07, 1-year survival was 90·6% (95% CI 90·2–90·9), 3-year survival was 81·0 % (95% CI 80·5–81·4), and 5-year survival was 77·9% (95% CI 77·4–78·3). For all cancers combined, 5-year survival rose from 76·1% (74·4–77·7) for 1999–2001, to 79·1% (77·3–80·7) for 2005–07 (hazard ratio 0·973, 95% CI 0·965–0·982, p<0·0001). The greatest improvements were in eastern Europe, where 5-year survival rose from 65·2% (95% CI 63·1–67·3) in 1999–2001, to 70·2% (67·9–72·3) in 2005–07. Europe-wide average yearly change in mortality (hazard ratio) was 0·939 (95% CI 0·919–0·960) for acute lymphoid leukaemia, 0·959 (0·933–0·986) for acute myeloid leukaemia, and 0·940 (0·897–0·984) for non-Hodgkin lymphoma. Mortality for all of Europe did not change significantly for Hodgkin's lymphoma, Burkitt's lymphoma, CNS tumours, neuroblastoma, Wilms' tumour, Ewing's sarcoma, osteosarcoma, and rhabdomyosarcoma. Disparities for 5-year survival persisted between countries and regions, ranging from 70% to 82% (for 2005–07). Interpretation: Several reasons might explain persisting inequalities. The lack of health-care resources is probably most important, especially in some eastern European countries with limited drug supply, lack of specialised centres with multidisciplinary teams, delayed diagnosis and treatment, poor management of treatment, and drug toxicity. In the short term, cross-border care and collaborative programmes could help to narrow the survival gaps in Europe. Funding: Italian Ministry of Health, European Commission, Compagnia di San Paolo Foundation. [ABSTRACT FROM AUTHOR]

Ultraviolet radiation (UVR) exposure has been inversely associated with Hodgkin lymphoma (HL) risk, but only inconsistently, only in a few studies, and without attention to HL heterogeneity. We conducted a pooled analysis of HL risk focusing on type and timing of UVR exposure and on disease subtypes by age, histology, and tumor-cell Epstein-Barr virus (EBV) status. Four case-control studies contributed 1320 HL cases and 6381 controls. We estimated lifetime, adulthood, and childhood UVR exposure and history of sunburn and sunlamp use. We used 2-stage estimation with mixed-effects models and weighted pooled effect estimates by inverse marginal variances. We observed statistically significant inverse associations with HL risk for UVR exposures during childhood and adulthood, sunburn history, and sunlamp use, but we found no significant doseresponse relationships. Risks were significant only for EBV-positive HL (pooled odds ratio, 0.56; 95% confidence interval, 0.35 to 0.91 for the highest overall UVR exposure category), with a significant linear trend for overall exposure (P = .03). Pooled relative risk estimates were not heterogeneous across studies. Increased UVR exposure may protect against HL, particularly EBV-positive HL. Plausible mechanisms involving UVR induction of regulatory T cells or the cellular DNA damage response suggest opportunities for new prevention targets. [ABSTRACT FROM AUTHOR]

Childhood head and neck cancers (HNC) are rare and represent a complex group of anatomical topographies. The aim of this study is to describe the distribution, the incidence and survival rates of children with malignant HNC in France. A population-based study was conducted between 2000 and 2015 in children less than 15 years with a diagnosis of HNC using the French National Registry of Childhood Cancers database (RNCE). Age-standardized incidence rates (ASR) and survival analysis were performed. The 1623 included HNC represented 5.6% of all cancers included in the RNCE. The thyroid was the leading tumor site category (26.6%), followed by head and neck soft tissue location (15.4%) and the nasopharynx (10.8%). The most common cancers were thyroid gland carcinomas (26.1%), rhabdomyosarcomas (23.9%) and Burkitt Lymphomas (8.6%). Nasopharynx cancers and soft-tissue sarcomas were statistically more frequent in boys, while thyroid carcinomas were significantly more frequent in girls. The annual ASR was 8.6 new cancer cases per million children. For all HNC combined, the 5-year overall survival (OS) was 87.7% [95%CI: 85.9–89.2]. There was no statistically significant variation in 5-year OS between 2000-2007 and 2008–2015. Epidemiological data on HNC distribution, incidence and survival contributes to better understand these tumors by quantifying their impact on the French population and assessing their burden. Regarding the exclusion of topographies and some histological origins performed by some authors, this report proposes new recommendations to study HNC in a pediatric population. • Main sites: thyroid (27%), pharynx (17%), and head and neck soft tissue (15%) • Histologies: carcinomas (37%), rhabdomyosarcomas (24%), Burkitt lymphomas (9%) • Annual age-standardized incidence rate, 8.6 per million children, stable over time • 5-year overall survival: 88%, lowest for rhabdoid tumors (29%), osteosarcomas (65%) • Better 5-year OS for H&N compared to all sites for neuroblastomas and Ewing tumors [ABSTRACT FROM AUTHOR]

This study aimed to describe cancer incidence (2000-2008) and survival (2000-2004) in France in adolescents and young adults (AYA). All cases of cancer diagnosed in 15-24 years, recorded by all French population-based registries (14% of the French population), over the 2000-2008 period, were included. Incidence change over time was described with the conventional annual percentage change (cAPC). The survival of cases diagnosed (2000-2004) was estimated using Kaplan-Meier method. A total of 1022 in adolescents and 1396 in young adults were diagnosed. Overall incidence rates were 219.4/106 in 15-19 year olds and 293.1/106 in 20-24 year olds. The most frequently diagnosed cancers in male AYA were malignant gonadal germ-cell tumors and Hodgkin's disease, and were melanoma, thyroid carcinoma, and Hodgkin's disease in females. The age-standardized rates appeared stable over time in AYA, with a cAPC of +2.0% ( P = 0.68). The 5-year overall survival for all cancers was different between genders and age groups, with 78.8% (95%CI: 75.6-82.0) for males and 85.2% (95%CI: 82.2-88.1) for females ( P = 0.01), and 78.5% (95%CI: 75.0-82.1) in 15-19 year olds and 84.3% (95% CI: 81.6-87.0) in 20-24 year olds ( P = 0.02). Noteworthy, the frequency and the distribution of tumor types in AYA are unique and different from the observed at any other age group. Survival in French AYA has improved over time. Epidemiological data might reflect major trends in the risk factors and preventive interventions. Thus, further research into etiology of cancers affecting AYA should become key priorities for cancer control among AYA. [ABSTRACT FROM AUTHOR]

BACKGROUND: Traffic is a source of environmental exposures, including benzene, which may be related to childhood leukemia. OBJECTIVES: A national registry-based case-control study [ESCALE (Etude Sur les Cancers et les Leucémies de l'Enfant, Study on Environmental and Genetic Risk Factors of Childhood Cancers and Leukemia)] carried out in France was used to assess the effect of exposure to road traffic exhaust fumes on the risk of childhood leukemia. METHODS: Over the study period, 2003-2004, 763 cases and 1,681 controls < 15 years old were included, and the controls were frequency matched with the cases on age and sex. The ESCALE data were collected by a standardized telephone interview of the mothers. Various indicators of exposure to traffic and pollution were determined using the geocoded addresses at the time of diagnosis for the cases and of interview for the controls. Indicators of the distance from, and density of, main roads and traffic nitrogen dioxide (NO2) concentrations derived from traffic emission data were used. Odds ratios (ORs) were estimated using unconditional regression models adjusted for potential confounders. RESULTS: Acute leukemia (AL) was significantly associated with estimates of traffic NO2 concentration at the place of residence > 27.7 µg/m3 compared with NO2 concentration < 21.9 µg/m3 [OR = 1.2; confidence interval (CI), 1.0-1.5] and with the presence of a heavy-traffic road within 500 m compared with the absence of a heavy-traffic road in the same area (OR = 2.0; 95% CI, 1.0-3.6). There was a significant association between AL and a high density of heavy-traffic roads within 500 m compared with the reference category with no heavy-traffic road within 500 m (OR = 2.2; 95% CI, 1.1-4.2), with a significant positive linear trend of the association of AL with the total length of heavy-traffic road within 500m. CONCLUSION: This study supports the hypothesis that living close to heavy-traffic roads may increase the risk of childhood leukemia. [ABSTRACT FROM AUTHOR]

BACKGROUND: Traffic is a source of environmental exposures, including benzene, which may be related to childhood leukemia. OBJECTIVES: A national registry-based case-control study [ESCALE (Etude Sur les Cancers et les Leucémies de l'Enfant, Study on Environmental and Genetic Risk Factors of Childhood Cancers and Leukemia)] carried out in France was used to assess the effect of exposure to road traffic exhaust fumes on the risk of childhood leukemia. METHODS: Over the study period, 2003-2004, 763 cases and 1,681 controls < 15 years old were included, and the controls were frequency matched with the cases on age and sex. The ESCALE data were collected by a standardized telephone interview of the mothers. Various indicators of exposure to traffic and pollution were determined using the geocoded addresses at the time of diagnosis for the cases and of interview for the controls. Indicators of the distance from, and density of, main roads and traffic nitrogen dioxide (NO2) concentrations derived from traffic emission data were used. Odds ratios (ORs) were estimated using unconditional regression models adjusted for potential confounders. RESULTS: Acute leukemia (AL) was significantly associated with estimates of traffic NO2 concentration at the place of residence > 27.7 µg/m3 compared with NO2 concentration < 21.9 µg/m3 [OR = 1.2; confidence interval (CI), 1.0-1.5] and with the presence of a heavy-traffic road within 500 m compared with the absence of a heavy-traffic road in the same area (OR = 2.0; 95% CI, 1.0-3.6). There was a significant association between AL and a high density of heavy-traffic roads within 500 m compared with the reference category with no heavy-traffic road within 500 m (OR = 2.2; 95% CI, 1.1-4.2), with a significant positive linear trend of the association of AL with the total length of heavy-traffic road within 500m. CONCLUSION: This study supports the hypothesis that living close to heavy-traffic roads may increase the risk of childhood leukemia. [ABSTRACT FROM AUTHOR]

This study investigated the role of factors considered related to early stimulation of the immune system in the etiology of childhood acute leukemia. The national registry-based case-control study ESCALE was carried out in France in 2003–2004. Population controls were frequency matched to cases on age and gender. Data were obtained from structured telephone questionnaires administered to mothers. Odds ratios were estimated using unconditional regression models adjusted for potential confounders. Included were 634 acute lymphoblastic leukemia cases, 86 acute myeloblastic leukemia cases, and 1,494 controls aged ≥1 year. Negative associations were observed between acute lymphoblastic leukemia and birth order (P for trend < 0.0001), attendance at a day-care center before age 1 year (odds ratio (OR) = 0.8, 95% confidence interval (CI): 0.6, 1.1), prolonged breastfeeding (OR = 0.7, 95% CI: 0.5, 1.0), repeated early common infections (OR = 0.7, 95% CI: 0.6, 0.9), regular contact with farm animals (OR = 0.6, 95% CI: 0.5, 0.8), frequent farm visits in early life (OR = 0.4, 95% CI: 0.3, 0.6), and history of asthma (OR = 0.7, 95% CI: 0.4, 1.0) or eczema (OR = 0.7, 95% CI: 0.6, 0.9). Results support the hypothesis that repeated early infections and asthma may play a role against childhood acute leukemia. [ABSTRACT FROM PUBLISHER]

Abstract: The aim of this study was to describe the overall survival after childhood cancer in France using follow-up data from regional population-based registries. The survival of children (aged under 15 years) diagnosed with a cancer during 1990–1999 was analysed. For all cancers, the survivals were, respectively, 90.3% [89.4–91.3] at 1-year, 75.2% [73.8–76.6] at 5 years and 72.2% [70.7–73.7] at 10 years. During the 1990s, the average improvement in the 5-year survival was +1.2% per year. Adjusted for gender, age, area of residence and stage, children with cancer diagnosed between 1995 and 1999 had a 0.80 reduced risk of dying compared with those whose cancer had been diagnosed between 1990 and 1994. The increase of survival at the population level reflects a global improvement in childhood cancer care. The Paediatric Registries, in association with the French Society of Childhood Cancer, are now collecting data to quantify on a national basis the other events, at least relapse and second cancers. [Copyright &y& Elsevier]

Abstract: Background: Determining the role of pre- and perinatal factors in the aetiology of childhood malignant central nervous (CNS) tumors, using data from the French national case–control study, ESCALE. Methods: ESCALE included all children in France less than 15 years old with a diagnosis of acute leukaemia, lymphoma, malignant CNS tumor, or neuroblastoma (2003–2004). In all, 209 malignant CNS tumor cases (80% of the eligible cases) and 1681 population-based controls (71%) were included using quotas ensuring frequency matching with the cases by age and gender. Case and control mothers were interviewed using a standardised telephone interview, which elicited birth characteristics, congenital malformation, maternal reproductive history, and use of assisted reproductive technologies for the index child. Results: The cases and controls did not differ in terms of gestational age at birth, birth weight, birth order, breastfeeding, or parental age at birth. There was no association between assisted reproduction for the index child and malignant CNS tumor (OR=1.1 [0.6–2.2]). A positive association between a maternal history of one miscarriage and malignant CNS tumor was observed (OR=1.4 [1.0–2.0], p <0.05), especially for glial cell tumors (other glioma: OR=2.0 [1.1–3.6]). Conclusion: The results suggest a possible association between a maternal history of one miscarriage and the risk of malignant CNS tumor. [Copyright &y& Elsevier]

The article presents an investigation that deals with the relationship between potential occupational risk factors and lymphoid malignancy (LM). The etiology of LM remains unknown except for some established risk factors. A multicenter hospital-based case-control study which includes 824 incident cases of non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), multiple myeloma, and lymphoproliferative syndrome and 752 frequency-matched controls is done in France. It is suggested that farming plays a role in most types of lymphoid malignancy.

OBJECTIVES: We investigated the role of household exposure to pesticides in the etiology of childhood hematopoietic malignancies. METHODS: The national registry-based case-control study ESCALE (Etude sur les cancers de l'enfant) was carried out in France over the period 2003-2004. Population controls were frequency matched with the cases on age and sex. Maternal household use of pesticides during pregnancy and paternal use during pregnancy or childhood were reported by the mothers in a structured telephone questionnaire. Insecticides (used at home, on pets, or for garden crops), herbicides, and fungicides were distinguished. We estimated odds ratios (ORs) using unconditional regression models closely adjusting for age, sex, degree of urbanization, and type of housing (flat or house). RESULTS: We included a total of 764 cases of acute leukemia (AL), 130 of Hodgkin lymphoma (HL), 166 of non-Hodgkin lymphoma (NHL), and 1,681 controls. Insecticide use during pregnancy was significantly associated with childhood AL [OR = 2.1; 95% confidence interval (CI), 1.7-2.5], both lymphoblastic and myeloblastic, NHL (OR = 1.8; 95% CI, 1.3-2.6), mainly for Burkitt lymphoma (OR = 2.7; 95% CI, 1.6-4.5), and mixed-cell HL (OR = 4.1; 95% CI, 1.4-11.8), but not nodular sclerosis HL (OR = 1.1; 95% CI, 0.6-1.9). Paternal household use of pesticides was also related to AL (OR = 1.5; 95% CI, 1.2-1.8) and NHL (OR = 1.7; 95% CI, 1.2-2.6); but for AL the relationships did not remain after adjustment for maternal pesticide use during pregnancy. CONCLUSION: The study findings strengthen the hypothesis that domestic use of pesticides may play a role in the etiology of childhood hematopoietic malignancies. The consistency of the findings with those of previous studies on AL raises the question of the advisability of preventing pesticide use by pregnant women. [ABSTRACT FROM AUTHOR]

We investigated the role of maternal alcohol and coffee drinking during pregnancy and that of parental smoking in the aetiology of childhood leukaemia. A French, population-based, case–control study was conducted, comparing 472 [407 acute lymphoblastic leukaemia (ALL) and 62 acute myeloblastic leukaemia] cases of childhood acute leukaemia (AL) and 567 population controls, frequency-matched with cases on age, gender and region of residence. Both case and control mothers filled in a comprehensive self-administered standardised questionnaire, eliciting detailed data on maternal alcohol and coffee consumption during pregnancy and parental smoking before, during and after pregnancy. Maternal alcohol consumption of more than 1 drink per day was related to ALL (OR = 2.8 [95% CI 1.8, 5.9]). While maternal coffee consumption was not significantly related to AL (OR = 1.4 [95% CI 0.9, 2.3]), highest intake of coffee (more than 3 cups per day) during pregnancy was associated with AL in children whose mothers were non-smokers (OR = 1.9 [95% CI 1.0, 3.5]). No association with parental smoking, either maternal or paternal, was observed with AL. The present results suggest a possible role of the highest consumption of alcohol by the mother during pregnancy in the aetiology of childhood AL. [ABSTRACT FROM AUTHOR]

The aim of the study was to identify the major heat waves (HW) that occurred in France from 1971 to 2003 and describe their impact on all-cause and cause-specific mortality. Heat waves were defined as periods of at least three consecutive days when the maximum and the minimum temperature, averaged over the whole France, were simultaneously greater than their respective 95th percentile. The underlying causes of death were regrouped into 18 categories. Heatstroke, hyperthermia and dehydration were assigned to the “heat-related causes” (HRC) category. The numbers of deaths observed ( O) during the identified HW were compared to those expected ( E) on the basis of the mortality rates reported for the three preceding years. Six HW were identified from the period 1971 to 2003. They were associated with great excess mortality (from 1,300 to 13,700 deaths). The observations are compatible with a moderate harvesting effect for four of the six HW. The mortality ratios increased with age for subjects aged over 55 years and were higher for women than for men over 75 years. For the six HW, the excess mortality was significant for almost all the causes of death: (1) the greatest excess mortality ( O– E) were observed for cardiovascular diseases, neoplasms, respiratory system diseases, HRC, ill-defined conditions and injury and poisoning, and (2) the mortality ratios ( O/ E) were highest for HRC, respiratory diseases, nervous system diseases, mental disorders, infectious diseases, and endocrine and nutritional diseases. Heat waves associated with excess mortality are not rare events in this temperate-climate country. The excess mortality is much greater than HRC mortality. Some populations are particularly vulnerable to HW: the elderly, women and people with some specific diseases. However, no segment of the population may be considered protected from the risks associated with HW. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: We investigated the role of maternal alcohol and coffee drinking and parental smoking on the risk of childhood acute leukemia in a multicenter case–control study. Methods: The study included 280 incident cases and 288 hospitalized controls, frequency matched with the cases by age, gender and center. Data collection was completed by face-to-face standardized interviews of the case and control mothers. Results: An association with maternal alcohol consumption during pregnancy was observed with acute lymphoid leukemia (ALL) (OR=2.0 [1.4–3.0]) and acute non-lymphoid leukemia (ANLL) (OR=2.6 [1.2–5.8]). Maternal coffee consumption during pregnancy was associated with childhood acute leukemia, ORs increasing in ALL with coffee consumption (OR=1.1 [0.7–1.8], OR=2.4 [1.3–4.7] and OR=3.1 [1.0–9.5], respectively, for ≤3, 4–8 and >8cups/day). No association with maternal smoking during pregnancy or parental smoking before or after the index child''s birth was observed. Discussion: Our results suggest an association with maternal alcohol and coffee drinking during pregnancy and call for further investigations. Besides, the present study does not support the hypothesis of an increase in the risk of childhood leukemia related to parental smoking. [Copyright &y& Elsevier]

The role of natural background radiation (NBR) in childhood acute leukemia (AL) remains unclear. Several large record based studies have recently reported heterogeneous results. Differences in exposure assessment timing may explain this heterogeneity. In a previous ecological study we did not observe any association between childhood AL incidence in France and NBR exposure at the time of diagnosis. With the same methodology, the present study focused on NBR exposure at the time of birth. Based on data from the French national registry of childhood cancer, we analyzed all AL together, and lymphoblastic and myeloid AL, separately. We included 6,059 childhood AL cases born and diagnosed in mainland France between 1990 and 2009. NBR levels in municipalities of residence at birth were estimated by cokriging models, using NBR measurements and precise geological data. The incidence rate ratio (IRR) per unit variation of exposure was estimated with Poisson regression models, with adjustment for socio-demographic indicators and ultraviolet radiation levels. NBR exposures were considered at the time of birth, and cumulatively from birth to diagnosis. We also estimated a total NBR dose to red-bone marrow (RBM). There was no evidence for an association between NBR exposure at birth and childhood AL incidence, neither overall (gamma radiation: IRR = 0.99 (0.94,1.05) per 50 nSv/h; radon: IRR = 0.97 (0.91,1.03) per 100 Bq/m3) nor for the main AL types. The conclusions were similar with the cumulative exposures, and the total RBM dose. The study was based on high quality incidence data, large numbers of AL cases, and validated models of NBR exposure assessment. In all, the results further support the hypothesis that NBR are not associated to childhood AL in France. • The initiation process of childhood leukemia might begin during the perinatal term. • Nationwide study on background radiation exposure at birth and childhood leukemia. • Complete registration of childhood leukemia in France (6,059 cases over 1990–2009). • Cockriging models based on radiation measurements (>10,000 sites) and geological maps. • Exposure to background radiation at birth not associated with childhood leukemia. [ABSTRACT FROM AUTHOR]

Pesticide exposure is suspected to play a role in the etiology of childhood leukemia (AL). Various sources of exposure have been explored, but few studies have investigated the risk of childhood AL in relation to residential exposure to agricultural pesticides. Since around 50% of France is agricultural land, with marked pesticide use, France is a suitable location to investigate for an association. We aimed to analyze the association between the agricultural crop density in the municipalities of France and the incidence of childhood AL between 1990 and 2014. 11,487 cases of AL diagnosed in children aged 0–14 years were registered by the French National Registry of Childhood Hematological Malignancies over 1990–2014. National agricultural census data for 1990, 2000 and 2010 were used to estimate the densities of the most common crops in France. The incidence of AL was estimated in the 35,512 municipalities, by age and gender, and 3 observation periods, and expressed as the standardized incidence ratio (SIR). We observed a moderate log-linear association between viticulture density and the incidence of AL, with a 3% increase in SIR for a 10% increase in viticulture density (SIRR = 1.03; 95%CI [1.00–1.06]). The association remained for lymphoblastic AL but not for myeloid AL. The association was stable after stratification by geographic area, age and period, and after adjustment on UV radiation and a French deprivation index. No consistent association was observed for other crop types. This nationwide study shows a moderate increase in incidence of childhood AL in municipalities where viticulture is common. Future individual studies are needed to know whether this observation is confirmed and related to particular use of pesticides. • Children living close to agricultural crops may be exposed to pesticides, and therefore at increased risk of leukemia. • Nationwide registry-based study on the link between crop density in the municipalities and incidence of childhood leukemia. • We found a moderate increase in incidence of childhood leukemia in municipalities with the highest density of viticulture. • Further works needed on individual exposures to pesticides used for viticulture and other crops close to the residences. [ABSTRACT FROM AUTHOR]