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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]

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.

Background: Several studies have addressed the potential seasonality of childhood acute leukaemia (AL) without conclusive results. Using data from the National Registry of Childhood Cancers over 1990-2014 in mainland France, we investigated the seasonal variations in childhood AL taken together, and lymphoblastic (ALL) and myeloid (AML) leukaemia separately.Methods: Assuming constant variations over 1990-2014, we used a Poisson regression model to evaluate variations in standardized incidence ratios (SIRs) by month of birth or diagnosis. A scan method for temporal cluster detection was used to identify windows of several consecutive months with high or low SIR. The yearly reproducibility of the observed monthly variations was then evaluated.Results: We included 11,528 AL, of which 9493 ALL and 1,843 AML. No seasonal variation was detected for ALL. With a clear seasonal pattern, differences in AML incidence rates were evidenced between January-April and May-December birth periods (SIR = 0.85, 95% CI 0.77-0.94 and SIR = 1.07, 95% CI 1.01-1.14, respectively). AML incidence variations by month of diagnosis were less clear-cut.Conclusion: Based on a large number of cases from a high-quality registry, we did not evidence any seasonality in ALL incidence rates but evidenced seasonal variations in AML incidence rates by month of birth. [ABSTRACT FROM AUTHOR]

Purpose: Wilms tumor (WT), or nephroblastoma, is an embryonic tumor that constitutes the most common renal tumor in children. Little is known about the etiology of WT. The aim of this study was to investigate whether maternal or perinatal characteristics were associated with the risk of WT.Methods: The ESTELLE study is a national-based case-control study that included 117 cases of WT and 1,100 controls younger than 11 years old. The cases were children diagnosed in France in 2010-2011 and the controls were frequency matched with cases by age and gender. The mothers of case and control children responded to a telephone questionnaire addressing sociodemographic and perinatal characteristics, childhood environment, and lifestyle. Unconditional logistic regression models adjusted on potential cofounders were used to estimate the odds ratios (OR) and their confidence intervals (95% CI).Results: High birth weight and the presence of congenital malformation were associated with WT (OR 1.9 [95% CI 1.0-3.7] and OR 2.5 [95% CI 1.1-5.8], respectively). No association with breastfeeding or folic acid supplementation was observed.Conclusions: Although potential recall bias cannot be excluded, our findings reinforce the hypothesis that high birth weight and the presence of congenital malformation may be associated with an increased risk of WT. Further investigations are needed to further elucidate the possible role of maternal characteristics in the etiology of WT. [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]

Neuroblastoma (NB) is the most common extra‐cranial tumour in children. Little is known about the aetiology of NB. The early age at onset and the embryonic nature suggest a role for perinatal exposures. We conducted a pooled analysis of two French national population‐based case–control studies to explore whether there was an association between parental smoking and alcohol consumption and the risk of NB. The mothers of 357 NB cases and 1,783 controls from general population, frequency matched by age and sex, were interviewed on demographic, socioeconomic and perinatal characteristics, maternal reproductive story, and life‐style and childhood environment. Unconditional logistic regression was used to estimate pooled odds ratios and 95% confidence intervals. A meta‐analysis of our findings with those of previous studies was also conducted. Maternal smoking during pregnancy was slightly more often reported for the cases (24.1%) than for the controls (19.7%) (OR 1.3 [95% CI 0.9–1.7]; summary OR from meta‐analysis 1.1 [95% CI 1.0–1.3]. Paternal smoking in the year before child's birth were not associated with NB as independent exposure (OR 1.1 [95% CI 0.9–1.4] but the association was stronger when both parents reported having smoked during pregnancy (OR 1.5 [95% CI 1.1–2.1]. No association was observed with maternal alcohol intake during pregnancy (OR 1.0 [95% CI 0.8–1.4], summary OR from meta‐analysis 1.0 [95% CI 0.9–1.2]. Our findings provide some evidence of an association between maternal smoking during pregnancy and NB and add another reason to recommend that women refrain from smoking during pregnancy. What's new? Neuroblastoma strikes early in life, which suggests an influence from risk factors that occur before birth. Here, the authors looked at parental smoking and alcohol drinking in a large population sample in France. Cases were collected by a nationwide registry, so the sample was very complete, and included 357 cases of neuroblastoma. The analysis revealed no association between maternal alcohol drinking and the cancer, nor between neuroblastoma and paternal smoking. They did identify a slight positive association with maternal smoking, and the effect was stronger if both parents smoked. [ABSTRACT FROM AUTHOR]

Purpose: Although some specific genetic syndromes such as neurofibromatosis (NF) have been identified as risk factor of childhood brain tumors (CBT), the potential role of inherited susceptibility in CBT has yet to be elucidated.Methods: To further investigate this, we conducted a pooled analysis of two nationwide case-control studies ESCALE and ESTELLE. The mothers of 509 CBT cases and 3,102 controls aged under 15 years who resided in France at diagnosis/interview, frequency-matched by age and gender, responded to a telephone interview conducted by trained interviewers. Pooled odds ratio (OR) and 95% confidence intervals (95% CI) were estimated using unconditional logistic regression.Results: CBT was significantly associated with the family history of cancer in relatives (OR 1.2, 95% CI 1.0-1.5). The OR was slightly higher for maternal relatives than for paternal relatives, and when at least two relatives had a history of cancer. CBT was significantly associated with a family history of brain tumor (OR 2.1, 95% CI 1.3-3.7). This association seemed stronger for first-degree relatives (mother, father, and siblings), for whom, by contrast, no association was seen for cancers other than CBT. No specificity by CBT subtypes or by age of the children were found for any of these findings.Conclusion: Our findings support the hypothesis of a familial susceptibility of CBT, not due to being a known NF carrier. [ABSTRACT FROM AUTHOR]

Purpose: Neuroblastoma (NB) is an embryonic tumor that occurs almost exclusively in infancy and early childhood. While considerable evidence suggests that it may be initiated during embryonic development, the etiology of NB is still unknown. The aim of this study was to explore whether there is an association between maternal use of household pesticides during pregnancy and the risk of NB in the offspring.Methods: We conducted a pooled analysis of two French national-based case-control studies. The mothers of 357 NB cases and 1,783 controls younger than 6 years, frequency-matched by age and gender, responded to a telephone interview that focused on sociodemographic and perinatal characteristics, childhood environment, and life-style. Unconditional logistic regression was used to estimate pooled odds ratios and 95% confidence intervals.Results: After controlling for matching variables, study of origin, and potential confounders, the maternal use of any type of pesticide during pregnancy was associated with NB (OR 1.5 [95% CI 1.2-1.9]). The most commonly used type of pesticides were insecticides and there was a positive association with their use alone (OR 1.4 [95% CI 1.1-1.9]) or with other pesticides (OR 2.0 [95% CI 1.1-3.4]).Conclusions: Although there is the potential for recall bias due to the study design, our findings add to the evidence of an association between the household use of pesticides and NB. Until a better study design can be found, our findings add yet another reason why to advise pregnant women to limit pesticide exposure during the periconceptional period. [ABSTRACT FROM AUTHOR]

Purpose: To investigate whether parental smoking around the time of pregnancy or maternal consumption of beverages (alcohol, coffee, or tea) during pregnancy were associated with the risk of CBT.Methods: We pooled data from two French national population-based case-control studies with similar designs conducted in 2003-2004 and 2010-2011. The mothers of 510 CBT cases (directly recruited from the national childhood cancer register) and 3,102 controls aged under 15 years, frequency matched by age and gender, were interviewed through telephone, which included questions about prenatal parental smoking and maternal consumption of alcohol, coffee and tea. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression, adjusted for age, sex and study of origin.Results: No association was seen between CBT and the mother smoking or drinking alcohol, coffee, or tea during the index pregnancy. The OR between CBT and paternal smoking in the year before birth (as reported by the mother) was 1.25 (95% CI 1.03, 1.52) with an OR of 1.09 (0.99, 1.19) for every 10 cigarettes per day (CPD) smoked. The association between paternal smoking and CBT appeared to be stronger in children diagnosed before the age of five years (OR 1.52, 95% CI 1.14, 2.02) and for astrocytoma (OR 1.86, 95% CI 1.26, 2.74).Conclusion: We found some evidence of a weak association between paternal smoking in the year before the child's birth and CBT, especially astrocytomas. These findings need to be replicated in other samples, using similar classifications of tumour subtypes. [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]

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]

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]

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]

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]

The article focuses on the evaluation of the ecological association between terrestrial and cosmic gamma radiation, indoor radon and acute leukemia among children in France. The cases of acute leukemia were recorded by the French National Registry of Childhood Leukemia and Lymphoma. Results of the study showed a retrained ecological association between childhood Acute Myelogenous Leukemia incidence and indoor radon. A case control study of residentially exposed children will have to make up of a large number of cases and controls with individual radon measurements and substantial contrasts in exposure.

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]

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]

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.

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]

High-dose ionizing radiation is an established risk factor for childhood central nervous system tumors (CNST) but the role of low doses remains debated. In particular, there are few studies of natural background radiation (NBR, gamma radiation and radon) and childhood CNST, and their results are inconclusive. This study aimed to investigate the ecological association between NBR exposure and childhood CNST incidence in France, considering childhood CNST overall and by subgroups. Incidence data were provided by the French national registry of childhood cancers, which has high completeness. We included 5471 childhood CNST cases registered over the period 2000-2012, and their municipality of residence at diagnosis was recorded. Municipality NBR exposures were estimated by cokriging models, using NBR measurements and additional geographic data. The incidence rate ratio (IRR) per unit variation of exposure was estimated with Poisson regression models. NBR exposures were considered at the time of diagnosis, and cumulatively from birth to diagnosis. In an exploratory analysis, the total brain dose due to NBR was used. Overall, there was no association between NBR exposure and childhood CNST incidence (IRR = 1.03 (0.98,1.09) per 50 nSv/h for gamma radiation, and IRR = 1.02 (0,96,1.07) per 100 Bq/m3 for radon). An association was suggested between pilocytic astrocytomas and gamma radiation (IRR = 1.12 (1.00,1.24) per 50 nSv/h) but not with radon (IRR = 1.07 (0.95,1.20) per 100 Bq/m3). Upward trends for this CNST subtype were also suggested with the cumulative exposures to gamma radiation and the total brain dose. NBR exposure was not associated with other CNST subgroups (ependymomas, embryonal tumors, and gliomas other than pilocytic astrocytomas). Adjustment for socio-demographic factors did not change the findings. Our study was based on high quality incidence data, large numbers of CNST cases, and validated models of NBR exposure assessment. Results suggest an association between gamma radiation, as a component of NBR, and pilocytic astrocytomas incidence in France. • Ecological study on childhood brain tumors and natural radiation in France. • Complete nationwide recording of childhood brain tumors (5471 cases, 2000-2012). • Cokriging models based on radiation measurements (>10,000 sites) and geological maps. • Gamma radiation associated with pilocytic astrocytoma incidence rate, not radon. • Natural radiation not associated to ependymomas, embryonal tumors and other gliomas. [ABSTRACT FROM AUTHOR]

Importance: Cancer is a leading cause of death among children worldwide. Treatments used for medically assisted reproduction (MAR) are suspected risk factors because of their potential for epigenetic disturbance and associated congenital malformations., Objective: To assess the risk of cancer, overall and by cancer type, among children born after MAR compared with children conceived naturally., Design, Setting, and Participants: For this cohort study, the French National Mother-Child Register (EPI-MERES) was searched for all live births that occurred in France between January 1, 2010, and December 31, 2021 (and followed up until June 30, 2022). The EPI-MERES was built from comprehensive data of the French National Health Data System. Data analysis was performed from December 1, 2021, to June 30, 2023., Exposure: Use of assisted reproduction technologies (ART), such as fresh embryo transfer (ET) or frozen ET (FET), and artificial insemination (AI)., Main Outcomes and Measures: The risk of cancer was compared, overall and by cancer type, among children born after fresh ET, FET, or AI and children conceived naturally, using Cox proportional hazards regression models adjusted for maternal and child characteristics at birth., Results: This study included 8 526 306 children with a mean (SD) age of 6.4 (3.4) years; 51.2% were boys, 96.4% were singletons, 12.1% were small for gestational age at birth, and 3.1% had a congenital malformation. There were 260 236 children (3.1%) born after MAR, including 133 965 (1.6%) after fresh ET, 66 165 (0.8%) after FET, and 60 106 (0.7%) after AI. A total of 9256 case patients with cancer were identified over a median follow-up of 6.7 (IQR, 3.7-9.6) years; 165, 57, and 70 were born after fresh ET, FET, and AI, respectively. The overall risk of cancer did not differ between children conceived naturally and those born after fresh ET (hazard ratio [HR], 1.12 [95% CI, 0.96 to 1.31]), FET (HR, 1.02 [95% CI, 0.78 to 1.32]), or AI (HR, 1.09 [95% CI, 0.86 to 1.38]). However, the risk of acute lymphoblastic leukemia was higher among children born after FET (20 case patients; HR 1.61 [95% CI, 1.04 to 2.50]; risk difference [RD], 23.2 [95% CI, 1.5 to 57.0] per million person-years) compared with children conceived naturally. Moreover, among children born between 2010 and 2015, the risk of leukemia was higher among children born after fresh ET (45 case patients; HR, 1.42 [95% CI, 1.06 to 1.92]; adjusted RD, 19.7 [95% CI, 2.8 to 43.2] per million person-years)., Conclusions and Relevance: The findings of this cohort study suggest that children born after FET or fresh ET had an increased risk of leukemia compared with children conceived naturally. This risk, although resulting in a limited number of cases, needs to be monitored in view of the continuous increase in the use of ART.

Background: Childhood cancer survival currently exceeds 80 % five years after diagnosis in high-income countries. In this study, we aimed to describe long-term trends and to investigate socioeconomic and spatial disparities in childhood cancer survival., Methods: The study included 28,073 cases recorded in the French National Registry of Childhood Cancers from 2000 to 2015. Contextual census data (deprivation indices, population density, spatial accessibility to general practitioners) were allocated to each case based on the residence at diagnosis. Overall survival (OS) and conditional 10-year OS for 5-year survivors were estimated for all cancers combined and by diagnostic group and subgroup. Comparisons were conducted by sex, age at diagnosis, period of diagnosis, and contextual indicators. Hazard ratios for death were estimated using Cox models., Results: All cancers combined, the OS reached 82.8 % [95 % CI: 82.4-83.3] at 5 years and 80.8 % [95 % CI: 80.3-81.3] at 10 years. Conditional 10-year OS of 5-year survivors reached 97.5 % [95 % CI: 97.3-97.7] and was higher than 95 % for all subgroups except osteosarcomas and most subgroups of the central nervous system. In addition to disparities by sex, age at diagnosis, and period of diagnosis, we observed a slight decrease in survival for cases living in the most deprived areas at diagnosis, not consistent across diagnostic groups., Conclusion: Our results confirm the high 5-year survival for childhood cancer and show an excellent 10-year conditional survival of 5-year survivors. Additional individual data are needed to clarify the factors underlying the slight decrease in childhood cancer survival observed in the most deprived areas., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: This study was undertaken to determine cancer survival and describe the spectrum of cancers diagnosed among French adolescent and young adult (AYA) population. Methods: All cases of cancer diagnosed in 15-24 years, recorded by all French population-based registries (18% of the French population), over the 2000-2016 period, were included. Age-standardized incidence rates, conventional annual percentage change (cAPC) of incidence over time, and 5-year overall survival (5yOS) were calculated. Results: We analyzed 2734 cancer diagnoses in adolescents and 4199 in young adults. Overall incidence rates were 231.9/10 6 in 15-19 year olds and 354.0/10 6 in 20-24 year olds. The most frequently diagnosed cancers in male AYA were malignant gonadal germ-cell tumors (GCT), Hodgkin lymphoma (HL), and malignant melanoma and were HL, thyroid carcinoma, and malignant melanoma in females. Cancer incidence was stable over time with a cAPC of 0.8% ( p  = 0.72). For all cancers combined, 5yOS was 86.6% (95% CI: 85.8-87.4), >85% for HL, non-Hodgkin lymphomas (NHL), GCT, thyroid carcinomas, and malignant melanomas, and around 60% and lower for osteosarcomas, Ewing tumors, hepatic carcinomas, and rhabdomyosarcomas. The 5yOS has significantly improved from 2000-2007 to 2008-2015 for all cancers pooled, with a substantial gain of 4% for 15-19 year olds and 3% for 20-24 year olds. Conclusion: Notwithstanding the encouraging results for some cancers, and overall, persistent poorer survivals in AYA were shown compared to children for acute lymphoblastic leukemia, osteosarcoma, Ewing tumor, rhabdomyosarcoma, and malignant hepatic tumors. These disparities require further investigation to identify and address the causes of these inferior outcomes.

Background: Few studies have assessed the relation between maternal prenatal pesticides use and childhood lymphoma risk, some reporting a positive association with non-Hodgkin lymphoma (NHL). We investigated the association between maternal exposure to pesticides during pregnancy and childhood Hodgkin (HL) and non-Hodgkin lymphoma., Methods: We pooled data from the two French national population-based case-control studies ESCALE (2003-2004) and ESTELLE (2010-2011). Data on domestic and occupational exposures to pesticides during pregnancy were obtained through standardised maternal interviews. Logistic regression models were used to compute odds ratios (OR) and 95% confidence intervals (CI) for HL and NHL, by pesticide category adjusted for potential confounders. Analyses by histological subtypes were also performed., Results: We included 328 H L, 305 non-Hodgkin NHL and 2,415 controls. Around 40% of control mothers reported having used pesticides during index pregnancy, of whom 95% reported insecticides use. Maternal use of herbicides and fungicides occurred mostly in combination with insecticides. Insecticides use was more frequently reported in cases than controls (OR NHL  = 1.6 [95%CI 1.3-2.1], p = 0.0001; OR HL  = 1.3 [95%CI 1.0-1.7], p = 0.03). This association appeared more marked for Burkitt lymphoma and mixed cellularity classical HL. No obvious association was observed with occupational pesticides exposure during pregnancy., Conclusion: These results suggest that maternal domestic use of insecticides during pregnancy might be related to both childhood NHL and HL. Further larger studies are urgently needed., (Copyright © 2020. Published by Elsevier Ltd.)

Background: On average 185 children are diagnosed each year in France with a cancer in their first year of life, representing 11 % of cancers diagnosed in children less than 15 years., Methods: A retrospective population-based observational study was conducted between 2000 and 2014 of all infants with a diagnosis of cancer using the National Registry of Childhood Cancers Database., Results: Out of 2760 cases of primary cancers in infancy, there were mainly neuroblastomas 30.1 %), central nervous system (CNS) tumors (16.1 %), leukemias (15.3 %), retinoblastomas (11.6 %), and Wilms tumors (6.9 %). Embryonal malignancies accounted for 55.2 % of cases. Most diagnoses showed a male excess, particularly for malignant gonadal germ-cell tumors (GCT) with a 17.5 sex-ratio. The annual incidence rate, 242.9 per million infants overall, was stable over the study period for all types of cancer. Most deaths occurred within the first month of life (70.8 % of deaths). The 5-year overall survival (5-y OS) was 81.0 % (95 %CI, 79.4-82.4) with large contrasts between diagnoses. The best 5-y OS (>85 %) were observed for retinoblastomas, carcinomas, nephroblastomas, GCT, neuroblastomas, and hepatoblastomas. Conversely, the lowest 5-y OS (<65 %) were observed for acute myeloid leukemias, CNS tumors, and lymphoid leukemias. We observed no substantial change over time (80.5 % [95 %CI, 77.7-82.9] in 2000-2004 and 82.6 % [95 %CI, 80.0-84.9] in 2010-2014) for all cancers combined. The same result has been found whatever the diagnostic group., Conclusion: Our results contribute to better understand these tumors by quantifying their impact on the French population and assessing the burden of some devastating infant cancers., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2020. Published by Elsevier Ltd.)

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., (© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: In order to evaluate at the population level the impact of the actions developed in France since 2004 to organize the care of adolescents and young adults (AYAs) with cancer, we conducted the present study to provide an unbiased view of the pathway of care of these patients., Methods: Using a population-based registry, we conducted a review of all cases of cancer diagnosed during 2012 and 2013 in 15- to 24-year-old patients living in nineteen French administrative areas., Results: The median times for diagnosis and treatment of the 993 included AYAs were 9 weeks (3-22) and 1 day (0-20), respectively. Delays in diagnosis were significantly longer in young adults than in adolescents, especially for soft-tissue sarcomas (48.7 weeks vs. 15.4 weeks, P = 0.04) and bone tumors (21.4 weeks vs. 10.1 weeks, P = 0.04). The first physicians seen by patients were mostly general practitioners (67.4%). Most patients (77.5%) were treated in adult units. Management decisions were taken within the context of a multidisciplinary team (MDT) in 85.3% of cases. MDT meetings that involved both pediatric and adult oncologists were uncommon (15.7% of patients). Twenty-six percent of patients were included in randomized or nonrandomized clinical studies. The proportion of inclusion was significantly higher in adolescents (39.5%) than in young adults (16.8%)., Conclusion: In France, pathways of care for AYAs are heterogeneous. It is necessary to organize a national network of expert centers with adequate medical skills and specific psychosocial support and facilities to provide the best possible care for these patients., (© 2018 Wiley Periodicals, Inc.)

Background: Few studies have investigated whether early infections and factors potentially related to early immune stimulation might be involved in the aetiology of childhood brain tumours (CBT). In this study, we investigated the associations between CBT with early day-care attendance, history of early common infections, atopic conditions (asthma/wheezing, eczema, allergic rhinitis), early farm residence/visits and contact with animals., Methods: We pooled data from two nationwide French case-control studies, the ESCALE and ESTELLE studies. Children with a CBT diagnosed between 1 and 14 years of age were identified directly from the French National Registry of Childhood Cancers, while population controls were recruited from telephone subscribers. Odds-ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression adjusted for potential confounders., Results: The analyses included 469 cases and 2719 controls. We found no association between attending a day-care centre (OR: 0.9, 95%CI: 0.7-1.2) or having had repeated common infections (OR: 0.9, 95%CI: 0.7-1.2) in the first year of life and the risk of CBT. There was also no association with a history of asthma/wheezing (OR: 0.8, 95%CI: 0.56-1.1). Farm visits (OR: 0.6, 95%CI: 0.5-0.8) as well as contact with pets (OR: 0.8, 95%CI: 0.6-1.0) in the first year of life were inversely associated with CBT., Conclusions: Our findings suggest a protective effect of early farm visits and contact with pets, but not with other markers of early immune stimulation. This might be related to immune stimulation but needs further investigation., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

In France, cancer hits around 1700 children (0-14 years) each year. The age-standardized incidence rate for all cancers combined is 152 cases per million children per year, with a sex ratio of 1.2. In other terms, one child out of 440 develops a cancer before the age of 15 in industrial countries. The most frequent cancers were leukaemia (29%), embryonal tumours apart central nervous system (25%), central nervous system tumour (23%) and lymphoma (12%). The incidence varies between countries with higher overall rates in industrialized countries. These variations may reflect differences in diagnostic techniques or registration or in the distribution of possible risk factors. Five-year survival after childhood cancer has dramatically improved in the last 30 years, reaching yet 80%.

This paper reports the latest survival data for French childhood cancer patients at the national level. Data from the two French National Registries of Childhood Cancer (Haematopoietic Malignancies and Solid Tumours) were used to describe survival outcomes for 15,479 children diagnosed with cancer between 2000 and 2008 in mainland France. The overall survival was 91.7% at 1 year, 86.9% at 2 years and 81.6% at 5 years. Relative survival did not differ from overall survival even for infants. Survival was lower among infants for lymphoblastic leukaemia and astrocytoma, but higher for neuroblastoma. For all cancers considered together, 5-year survival increased from 79.5% in the first (2000-2002) diagnostic period to 83.2% in the last (2006-2008) period. The improvement was significant for leukaemia, both myeloid and lymphoid, central nervous system tumours (ependymoma) and neuroblastoma. The results remained valid in the multivariate analysis, and, for all cancers combined, the risk of death decreased by 20% between 2000-2002 and 2006-2008. The figures are consistent with various international estimates and are the result of progress in treatment regimens and collaborative clinical trials. The challenge for the French registries is now to study the long-term follow-up of survivors to estimate the incidence of long-term morbidities and adverse effects of treatments.

Previous epidemiological studies and quantitative risk assessments (QRA) have suggested that natural background radiation may be a cause of childhood leukemia. The present work uses a QRA approach to predict the excess risk of childhood leukemia in France related to three components of natural radiation: radon, cosmic rays and terrestrial gamma rays, using excess relative and absolute risk models proposed by the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR). Both models were developed from the Life Span Study (LSS) of Japanese A-bomb survivors. Previous risk assessments were extended by considering uncertainties in radiation-related leukemia risk model parameters as part of this process, within a Bayesian framework. Estimated red bone marrow doses cumulated during childhood by the average French child due to radon, terrestrial gamma and cosmic rays are 4.4, 7.5 and 4.3 mSv, respectively. The excess fractions of cases (expressed as percentages) associated with these sources of natural radiation are 20 % [95 % credible interval (CI) 0-68 %] and 4 % (95 % CI 0-11 %) under the excess relative and excess absolute risk models, respectively. The large CIs, as well as the different point estimates obtained under these two models, highlight the uncertainties in predictions of radiation-related childhood leukemia risks. These results are only valid provided that models developed from the LSS can be transferred to the population of French children and to chronic natural radiation exposures, and must be considered in view of the currently limited knowledge concerning other potential risk factors for childhood leukemia. Last, they emphasize the need for further epidemiological investigations of the effects of natural radiation on childhood leukemia to reduce uncertainties and help refine radiation protection standards.

Purpose: This study aimed to analyze the associations between childhood acute leukemia (AL) and maternal caffeinated beverage consumption during pregnancy, and to explore interactions between caffeinated and alcoholic beverage consumption and polymorphisms of enzymes involved in caffeine and ethanol metabolisms., Methods: The data were generated by the French ESCALE study, which included 764 AL cases and 1,681 controls in 2003-2004. The case and control mothers were interviewed on their consumption habits during pregnancy using a standardized questionnaire. Genotypes of the candidate alleles (NAT2*5 rs1801280, ADH1C*2 rs698 and rs1693482, CYP2E1*5 rs2031920 and rs3813867) were obtained using high-throughput genotyping and imputation data for 493 AL cases and 549 controls with at least two grandparents born in Europe., Results: Maternal regular coffee consumption during pregnancy was associated with childhood AL (OR = 1.2 [1.0-1.5], p = 0.02); the odds ratios increased linearly with daily intake (p for trend <0.001; >2 cups per day vs. no or less than 1 cup per week: AL: OR = 1.6 [1.2-2.1], lymphoblastic AL: OR = 1.5 [1.1-2.0], myeloblastic AL: OR = 2.4 [1.3-4.3]). The association was slightly more marked for children born to non-smoking mothers. Lymphoblastic AL was also associated with cola soda drinking (OR = 1.3 [1.0-1.5], p = 0.02). No significant gene-environment interactions with coffee, tea, cola soda, or alcohol drinking were observed., Conclusion: This study provides additional evidence that maternal coffee consumption during pregnancy may be associated with childhood AL. Coffee consumption is a prevalent habit and its potential involvement in childhood AL needs to be considered further.

The aim of this work is to study the risk of childhood acute leukemia (AL) around French nuclear power plants (NPPs). The nationwide Geocap case-control study included the 2,753 cases diagnosed in mainland France over 2002-2007 and 30,000 contemporaneous population controls. The last addresses were geocoded and located around the 19 NPPs. The study used distance to NPPs and a dose-based geographic zoning (DBGZ), based on the estimated dose to bone marrow related to NPP gaseous discharges. An odds ratio (OR) of 1.9 [1.0-3.3], based on 14 cases, was evidenced for children living within 5 km of NPPs compared to those living 20 km or further away, and a very similar association was observed in the concomitant incidence study (standardized incidence ratio (SIR)=1.9 [1.0-3.2]). These results were similar for all the 5-year-age groups. They persisted after stratification for several contextual characteristics of the municipalities of residence. Conversely, using the DBGZ resulted in OR and SIR close to one in all of the dose categories. There was no increase in AL incidence over 1990-2001 and over the entire 1990-2007 period. The results suggest a possible excess risk of AL in the close vicinity of French NPPs in 2002-2007. The absence of any association with the DBGZ may indicate that the association is not explained by NPP gaseous discharges. Overall, the findings call for investigation for potential risk factors related to the vicinity of NPP and collaborative analysis of multisite studies conducted in various countries., (Copyright © 2012 UICC.)

Childhood acute leukaemia (AL) accounts for a third of childhood cancers. Analysing the spatial distribution of the incidence of AL and its lymphoblastic and myeloblastic subtypes may contribute to the identification of risk factors. This national registry-based study aimed to evaluate global spatial heterogeneity in the incidence rates of AL and to detect clusters in France over the period 1990-2006 on the 'living-zone' scale. Between 1990 and 2006, 7675 cases of AL were registered in the National Registry of Childhood Haematopoietic malignancies. Their spatial distribution in the 1895 'living zone' was first evaluated with two tests for global spatial heterogeneity (Potthoff-Witthinghill and Rogerson's tests) and then with the SaTScan and FleXScan methods, which aim to locate spatial and space-time clusters. Over 1990-2006, no spatial heterogeneity of AL or its subtypes was evidenced. In addition, none of the most likely clusters identified with SaTScan and FleXScan over the whole period was significant, and the systematic search for space-time clusters yielded nonsignificant results. However, when three subperiods were considered, five statistically significant nonoverlapping spatial clusters were identified. This study did not find evidence of any global spatial heterogeneity of AL incidence rates in France over the period 1990-2006. Although no significant spatial cluster was detected over the whole period, the study identified a few significant spatial clusters in specific periods. Even though the significance levels of those clusters do not strongly support the existence of local risk factors, the clusters may still reflect a slight impact of shared risk factors, including background environmental exposures, which require further investigation.

Background: In France, as in other countries, there is a need for a population-based view of access to care and modalities of treatment for adolescents with cancer., Procedure: Using a population-based registration, we report pathways of care for 15-19-year-old patients, diagnosed with cancer in 2006 and 2007, living in six French regions, accounting for 41% of the French population., Results: The median times (inter-quartile range) for diagnosis and treatment of the 594 included adolescents were 8 weeks (3-17) and 3 days (0-16), respectively. First physicians met by the patients were mostly general practitioners (59%). Seventeen percent of patients were firstly seen on emergency wards. Most of the patients (82%) were treated in an adult environment. Management decisions were taken within the context of a multi-disciplinary team (MDT) in 54% of cases. Twenty-seven percent of patients were included in randomized or non-randomized clinical studies: percentage depended on the tumor type and on the number of on-going trials at the study period. Fifteen percent of patients were included in pediatric studies, 7% in adult studies, and 5% in studies including both adults and children., Conclusions: The pathways of care for French adolescent patients with cancer are heterogeneous. Our results reveal differences in MDT meetings according to tumor types and a lack of effective collaboration between pediatric and adult wards. Efforts must be made to develop cancer networks to ensure that adolescents receive the optimal care in a suitable environment., (Copyright © 2011 Wiley Periodicals, Inc.)

Background: For many years, the detection of clusters has been of great public health interest. Several detection methods have been developed, the most famous of which is the circular scan method. The present study, which was conducted in the context of a rare disease distributed over a large territory (7675 cases registered over 17 years and located in 1895 units), aimed to evaluate the performance of several of the methods in realistic hot-spot cluster situations., Methods: All the methods considered aim to identify the most likely cluster area, i.e. the zone that maximizes the likelihood ratio function, among a set of cluster candidates. The circular and elliptic scan methods were developed to detect regularly shaped clusters. Four other methods that focus on irregularly shaped clusters were also considered (the flexible scan method, the genetic algorithm method, and the double connected and maximum linkage spatial scan methods). The power of the methods was evaluated via Monte Carlo simulations under 27 alternative scenarios that corresponded to three cluster population sizes (20, 45 and 115 expected cases), three cluster shapes (linear, U-shaped and compact) and three relative risk values (1.5, 2.0 and 3.0)., Results: Three situations emerged from this power study. All the methods failed to detect the smallest clusters with a relative risk lower than 3.0. The power to detect the largest cluster with relative risk of 1.5 was markedly better for all methods, but, at most, half of the true cluster was captured. For other clusters, either large or with the highest relative risk, the standard elliptic scan method appeared to be the best method to detect linear clusters, while the flexible scan method localized the U-shaped clusters more precisely than other methods. Large compact clusters were detected well by all methods, with better results for the circular and elliptic scan methods., Conclusions: The elliptic scan method and flexible scan method seemed the most able to detect clusters of a rare disease in a large territory. However, the probability of detecting small clusters with relative risk lower than 3.0 remained low with all the methods tested.

Objectives: Investigating the role of occupational exposure to solvents in the occurrence of lymphoid neoplasms (LNs) in men., Methods: The data were generated by a French hospital-based case-control study, conducted in six centres in 2000-2004. The cases were incident cases aged 18-75 years with a diagnosis of LN. During the same period, controls of the same age and gender as the cases were recruited in the same hospitals, mainly in the orthopaedic and rheumatological departments. Exposure to solvents was assessed using standardised occupational questionnaires and case-by-case expert assessment. Specific quantification of benzene exposure was attempted. The analyses included 491 male patients (244 cases of non-Hodgkin's lymphoma (NHL), 87 of Hodgkin's lymphoma, 104 of lymphoproliferative syndrome and 56 of multiple myeloma) and 456 male controls. Unconditional logistic regressions were used to estimate OR and 95% CI., Results: Solvent exposure, all solvents considered together, was marginally associated with NHL (OR=1.4 (1.0 to 2.0) p=0.06), but not with other LNs. No association with the main chemical series of solvents was observed. There was no trend with the average intensity or frequency of exposure. Exposure to pure benzene was not significantly related to NHL (OR=3.4 (0.8 to 15.0)). The highest maximum intensities of benzene exposure were associated with diffuse large cell lymphoma (OR=2.1 (1.0 to 4.6))., Conclusion: The results of the present study provide estimates compatible with the hypothesis that exposures to pure benzene and high benzene intensities may play a role in some NHL. There was no evidence for a role of other organic solvents in the occurrence of LN.

Aim: To determine the epidemiology of myeloid leukaemia (ML) in children with Down syndrome (DS) and the efficacy of two approaches, low-dose cytarabine-based regimen (LDC) and standard-dose intensive chemotherapy (SD)., Procedure: All children with Down syndrome aged from 2 months to 15 years with ML/myelodysplasia registered in the French registry between January 1990 and December 2003 were included., Results: Forty-four patients were included. The median age was 1.75 years. The French-America-British subtypes were as follows: M7: 24, M0: 6, M2: 5, M6: 2. Forty-three patients were treated with curative prospect, 20 patients with LDC regimen and 22 according to SD protocols, 1 was given the LDC regimen plus autologous stem-cell transplantation. The event-free survival (EFS) and overall survival (OS) at 5 years were 64.4% and 76.8%. At 5 years, OS in LDC and SD groups were 65% and 85.9% (P = 0.08). EFS were 45% and 80.3% respectively (P < 0.01)., Conclusion: Children with DS can adequately tolerate SD chemotherapy with a significant superiority of EFS relative to LDC. We suggest that higher levels of cure can be obtained in DS-ML with SD chemotherapy including cytarabine and anthracyclines., (Copyright 2010 Wiley-Liss, Inc.)

The French National Registry of Childhood Haematopoietic Malignancies and the French National Registry of Childhood Solid Tumours jointly ensure the surveillance of cancer in children aged less than 15 years in mainland France. During the period 2000-2004, the registries recorded a total of 8473 cases: 3446 cases of haematological malignancies and 5027 cases of solid tumours. The average number of sources per case was 2.7 and diagnosis was documented by cytology/histology in 94% of cases, ensuring high quality data. The age-standardized incidence rate for all cancers combined was 156.6 cases per million children per year, with a sex ratio of 1.2. The most frequent cancers were leukaemia (29%), central nervous system tumour (23%), lymphoma (12%) and neuroblastoma (8%). In France, an estimated one out of every 440 children presents with cancer before the age of 15 years. The incidence rates are close to those of other industrialized countries, but somewhat higher than those estimated by the French local registries for the period 1990-1999, probably because of improved methodology or perhaps a real increase in some rates. The French National Registries of Childhood Cancer have shown that they are able to fulfil public health surveillance missions satisfactorily and support the national programme for research on childhood cancer.

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.

Spatial variations in childhood acute leukaemia (AL) incidence rates were investigated by département, in mainland France, over the period 1990-2004. This is the first spatial study of this incidence to cover a 15-year period. French National Registry of Childhood Haematological Malignancies data and population counts by type of leukaemia (AL, acute lymphoblastic leukaemia, acute myeloblastic leukaemia), time period (1990-2004, 1990-1994, 1995-1999 and 2000-2004), sex, and age group (0-14, 0-4, 5-9 and 10-14 years of age) were considered. The overall homogeneity of the relative risks of leukaemia was tested, as well as comparison to 1 of each relative risk by the exact Poisson test. To give a more stable estimate of the underlying relative risk pattern than that provided by the local standardized incidence ratios (SIRs), Bayesian hierarchical models using four different spatial priors have been produced: the parametric BYM and CAR models, and two semiparametric models. Very slight overall heterogeneity was observed on the whole AL data set (SIR overdispersion 18.6%, P=0.10). Irrespective of the model, the ranges of the smoothed SIRs exhibited considerable shrinkage relative to the ranges of the local SIRs. The associated maps were slightly heterogeneous; the smoothed SIRs of overall acute lymphoblastic leukaemia of the south-west départements were slightly higher than those of the north-east. The results, however, did not remain stable when investigated by leukaemia type, time period, sex or age group. No spatial heterogeneity of childhood AL incidence on the département scale was observed but that does not exclude spatial heterogeneity on other scales.

Objectives: Investigating the role of parental smoking and maternal alcohol consumption in the etiology of childhood hematopoietic malignancies., Methods: The national registry-based case-control study ESCALE was carried out in France over the period 2003-2004. Population controls were frequency matched with the cases on age and gender. Maternal smoking and alcohol consumption during pregnancy and paternal smoking since before conception were reported by the mothers in a structured telephone questionnaire. Odds ratios (OR) were estimated using unconditional regression models closely adjusted for potential confounders., Results: A total of 765 cases of acute leukemia (AL), 130 of Hodgkin's lymphoma (HL), 165 of non-Hodgkin's lymphoma (NHL) and 1681 controls were included. Paternal smoking was significantly associated with childhood ALL (OR = 1.4 [1.1-1.7]), AML (OR = 1.5 [1.0-2.3]), Burkitt (OR = 2.0 [1.2-3.2]), and anaplastic large cell (OR = 3.2 [1.2-9.1]) NHL. For the four diseases, the ORs significantly increased with the number of cigarettes smoked. No association with HL or with other types of NHL was observed. The associations with maternal alcohol consumption and cigarette smoking during pregnancy were less consistent., Conclusion: The results support the hypothesis that only paternal smoking, and not maternal alcohol consumption or cigarette smoking, plays a role in childhood hematopoietic malignancies.

Context: Long-term studies of tolerance to perinatal exposure to antiretroviral nucleoside reverse transcriptase inhibitors are required, in view of the potential genotoxicity of some of these molecules., Objective: To evaluate the incidence of cancers in uninfected children born to HIV-infected mothers., Method: Cancers were detected in a nationwide prospective cohort of children born to HIV-infected mothers by standardized questionnaire during the prospective follow-up period of 2 years; thereafter, they were detected by spontaneous pharmacovigilance declaration and by crosschecking data with the national registries of childhood cancer. Standardized incidence ratio for incidence comparisons with general population., Results: Ten cases of cancer were detected among the 9127 exposed HIV-uninfected children (median age: 5.4 years, 53 052 person-years of follow-up). The overall incidence did not differ significantly from that expected for the general population: 10 cases observed versus 8.9 and 9.6 expected depending on whether 1990-1999 or 2000-2004 national rates were used as reference [standardized incidence ratio of 1.1 (0.3-1.5) and 1.0 (0.5-1.9)]. Five cases of central nervous system cancer were observed (standardized incidence ratio of 3.1 [1.0-7.2] P = 0.05 and 2.4 [0.8-5.6], P = 0.12). The relative risk of cancer for children exposed to didanosine-lamivudine combination was higher than that for zidovudine monotherapy [hazard ratio: 13.6 (2.5-73.9)]., Conclusion: This study did not evidence an overall increase in cancer risk in nucleoside reverse transcriptase inhibitor exposed children until 5 years of age. Results suggesting associations with specific nucleoside reverse transcriptase inhibitor combinations need further investigations. A longer surveillance, including differential analysis of the different cancer sites and various nucleoside reverse transcriptase inhibitors administered is warranted.