Nonchromosomal birth defects and risk of childhood acute leukemia: An assessment in 15 000 leukemia cases and 46 000 controls from the Childhood Cancer and Leukemia International Consortium.

Although recent studies have demonstrated associations between nonchromosomal birth defects and several pediatric cancers, less is known about their role on childhood leukemia susceptibility. Using data from the Childhood Cancer and Leukemia International Consortium, we evaluated associations between nonchromosomal birth defects and childhood leukemia. Pooling consortium data from 18 questionnaire-based and three registry-based case-control studies across 13 countries, we used multivariable logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between a spectrum of birth defects and leukemia. Our analyses included acute lymphoblastic leukemia (ALL, n = 13 115) and acute myeloid leukemia (AML, n = 2120) cases, along with 46 172 controls. We used the false discovery rate to account for multiple comparisons. In the questionnaire-based studies, the prevalence of birth defects was 5% among cases vs 4% in controls, whereas, in the registry-based studies, the prevalence was 11% among cases vs 7% in controls. In pooled adjusted analyses, there were several notable associations, including (1) digestive system defects and ALL (OR = 2.70, 95% CI: 1.46-4.98); (2) congenital anomalies of the heart and circulatory system and AML (OR = 2.86, 95% CI: 1.81-4.52) and (3) nervous system defects and AML (OR = 4.23, 95% CI: 1.50-11.89). Effect sizes were generally larger in registry-based studies. Overall, our results could point to novel genetic and environmental factors associated with birth defects that could also increase leukemia susceptibility. Additionally, differences between questionnaire- and registry-based studies point to the importance of complementary sources of birth defect phenotype data when exploring these associations.

Breastfeeding and risk of childhood brain tumors: a report from the Childhood Cancer and Leukemia International Consortium.

PURPOSE: Studies report mixed findings regarding the association of breastfeeding with childhood brain tumors (CBT), the leading causes of cancer-related mortality in young people. Our objective was to determine whether breastfeeding is associated with CBT incidence. METHODS: We pooled data on N = 2610 cases with CBT (including 697 cases with astrocytoma, 447 cases with medulloblastoma/primitive neuroectodermal tumor [PNET], 167 cases with ependymoma) and N = 8128 age- and sex-matched controls in the Childhood Cancer and Leukemia International Consortium. We computed unconditional logistic regression models to estimate the odds ratio (OR) and 95% confidence interval (CI) of CBT, astrocytoma, medulloblastoma/PNET, and ependymoma according to breastfeeding status, adjusting for study, sex, mode of delivery, birthweight, age at diagnosis/interview, maternal age at delivery, maternal educational attainment, and maternal race/ethnicity. We evaluated any breastfeeding versus none and breastfeeding ≥ 6 months versus none. We subsequently performed random effects meta-analysis to confirm our findings, identify potential sources of heterogeneity, and evaluate for outliers or influential studies. RESULTS: Breastfeeding was reported by 64.8% of control mothers and 64.5% of case mothers and was not associated with CBT (OR 1.04, 95% CI 0.94-1.15), astrocytoma (OR 1.01, 95% CI 0.87-1.17), medulloblastoma/PNET (OR 1.11, 95% CI 0.93-1.32), or ependymoma (OR 1.06, 95% CI 0.81-1.40). Results were similar when we restricted to breastfeeding ≥ 6 months and in meta-analyses. CONCLUSION: Our data suggest that breastfeeding does not protect against CBT.

Pediatric Tumors and Developmental Anomalies: A French Nationwide Cohort Study.

OBJECTIVE: To assess the associations between congenital abnormalities and pediatric malignancies and evaluate the potential underlying molecular basis by collecting information on pediatric patients with cancer and congenital abnormalities. STUDY DESIGN: Tumeur Et Développement is a national, prospective, and retrospective multicenter study recording data of children with cancer and congenital abnormalities. When feasible, blood and tumoral samples are collected for virtual biobanking. RESULTS: From June 2013 to December 2019, 679 associations between pediatric cancers and congenital abnormalities were recorded. The most represented cancers were central nervous system tumors (n = 139; 20%), leukemia and myelodysplastic syndromes (n = 123; 18.1%), and renal tumors (n = 101; 15%). Congenital abnormalities were not related to any known genetic disorder in 66.5% of cases. In this group, the most common anomaly was intellectual disability (22.3%), followed by musculoskeletal (14.2%) and genitourinary anomalies (12.4%). Intellectual disability was mostly associated with hematologic malignancies. Embryonic tumors (neuroblastoma, Wilms tumor, and rhabdomyosarcoma) were associated with consistent abnormalities, sometimes with a close anatomical neighborhood between the abnormality and the neoplasm. CONCLUSIONS: In the first Tumeur Et Développement analysis, 3 major themes have been identified: (1) germline mutations with or without known cancer predisposition, (2) postzygotic events responsible for genomic mosaicism, (3) coincidental associations. New pathways involved in cancer development need to be investigated to improve our understanding of childhood cancers.

The feasibility of implementing Toronto childhood cancer stage guidelines and estimating the impact on outcome for childhood cancers in seven pediatric oncology units in sub-Saharan Africa. A study from the Franco-African Pediatric Oncology Group.

BACKGROUND: The improvement of childhood cancer outcome is determined by early diagnosis, effective treatment, supportive care, and adequate medical follow-up. Stage at diagnosis may reflect timeliness of diagnosis, therefore standardized registration of stage is essential for interpretation of regional differences and time trends in survival. Here, we describe the feasibility of implementing the Toronto Childhood Cancer Stage Guidelines (hereafter Toronto Guidelines [TG]) in the hospital-based cancer registry of the Franco-African Pediatric Oncology Group (GFAOP), and assess the impact of TG stage on outcome in pediatric oncology units (POUs) in seven low- and middle-income countries in sub-Saharan Africa (SSA). METHODS: All cancer patients diagnosed before 15 years of age with one of the 15 cancer types defined in TG, resident in one of the participating countries, and attending one of the selected POUs in 2017-2019 were included. Stage was assigned according to TG. Patients were followed-up for vital status for at least 12 months post diagnosis. Survival at 3, 6, and 12 months was calculated using Kaplan-Meier method and compared between POUs and tumor groups using log-rank test. RESULTS: TG stage was assigned to 1772 of 2446 (89%) cases diagnosed with one of 11 cancer types. It was not possible to assign TG stage to acute lymphoblastic leukemia (ALL) and the three types of the central nervous system tumors included in the TG. One-year overall survival (OS) was 58% [95% confidence interval: 55-60] and varied between POUs. Survival declined with increasing stage for four tumor types and was statistically significant for two. CONCLUSION: Except for ALL and brain tumors, we demonstrated feasibility of TG implementation for childhood solid cancers in participating POUs in SSA, and provided a baseline assessment of childhood cancer outcomes against which future stage distribution and survival can be measured as timelines of diagnosis improve over time within the GFAOP network.

Infant feeding practices and childhood acute leukemia: Findings from the Childhood Cancer & Leukemia International Consortium.

Increasing evidence suggests that breastfeeding may protect from childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). However, most studies have limited their analyses to any breastfeeding, and only a few data have examined exclusive breastfeeding, or other exposures such as formula milk. We performed pooled analyses and individual participant data metaanalyses of data from 16 studies (N = 17 189 controls; N = 10 782 ALL and N = 1690 AML cases) from the Childhood Leukemia International Consortium (CLIC) to characterize the associations of breastfeeding duration with ALL and AML, as well as exclusive breastfeeding duration and age at introduction to formula with ALL. In unconditional multivariable logistic regression analyses of pooled data, we observed decreased odds of ALL among children breastfed 4 to 6 months (0.88, 95% CI 0.81-0.96) or 7 to 12 months (OR 0.85, 0.79-0.92). We observed a similar inverse association between breastfeeding ≥4 months and AML (0.82, 95% CI 0.71-0.95). Odds of ALL were reduced among children exclusively breastfed 4 to 6 months (OR 0.73, 95% CI 0.63-0.85) or 7 to 12 months (OR 0.70, 95% CI 0.53-0.92). Random effects metaanalyses produced similar estimates, and findings were unchanged in sensitivity analyses adjusted for race/ethnicity or mode of delivery, restricted to children diagnosed ≥1 year of age or diagnosed with B-ALL. Our pooled analyses indicate that longer breastfeeding is associated with decreased odds of ALL and AML. Few risk factors for ALL and AML have been described, therefore our findings highlight the need to promote breastfeeding for leukemia prevention.

Allergies, genetic polymorphisms of Th2 interleukins, and childhood acute lymphoblastic leukemia: The ESTELLE study.

CONTEXT: A negative association between a history of allergy and childhood acute lymphoblastic leukemia (ALL) has been reported in previous studies, but remains debated. This work aimed to investigate this association accounting for genetic polymorphisms of the Th2 pathway cytokines (IL4, IL10, IL13, and IL4R). METHODS: Analyses were based on the French case-control study ESTELLE (2010-2011). The complete sample included 629 ALL cases and 1421 population-based controls frequency-matched on age and gender. The child's medical history was collected through standardized maternal interview. Biological samples were collected, and genotyping data were available for 411 cases and 704 controls of European origin. Odds ratios (OR) were estimated using unconditional regression models adjusted for potential confounders. RESULTS: In the complete sample, a significant inverse association was observed between ALL and reported history of allergic rhinitis or sinusitis (OR = 0.65 [0.42-0.98]; P = 0.04), but there was no obvious association with allergies overall. There was an interaction between genetic polymorphisms in IL4 and IL4R (Pinteraction = 0.003), as well as a gene-environment interaction between IL4R-rs1801275 and a reported history of asthma (IOR = 0.23; Pint  = 0.008) and eczema (IOR = 0.47; Pint  = 0.06). We observed no interaction with the candidate polymorphisms in IL4 and IL13. CONCLUSION: These results suggest that the association between allergic symptoms and childhood ALL could be modified by IL4R-rs1801275, and that this variant could also interact with a functional variant in IL4 gene. Although they warrant confirmation, these results could help understand the pathological mechanisms under the reported inverse association between allergy and childhood ALL.

Herbicide use in farming and other jobs in relation to non-Hodgkin's lymphoma (NHL) risk.

OBJECTIVES: Given mixed evidence for carcinogenicity of current-use herbicides, we studied the relationship between occupational herbicide use and risk of non-Hodgkin's lymphoma (NHL) in a large, pooled study. METHODS: We pooled data from 10 case-control studies participating in the International Lymphoma Epidemiology Consortium, including 9229 cases and 9626 controls from North America, the European Union and Australia. Herbicide use was coded from self-report or by expert assessment in the individual studies, for herbicide groups (eg, phenoxy herbicides) and active ingredients (eg, 2,4-dichlorophenoxyacetic acid (2,4-D), glyphosate). The association between each herbicide and NHL risk was estimated using logistic regression to produce ORs and 95% CIs, with adjustment for sociodemographic factors, farming and other pesticides. RESULTS: We found no substantial association of all NHL risk with ever-use of any herbicide (OR=1.10, 95% CI: 0.94 to 1.29), nor with herbicide groups or active ingredients. Elevations in risk were observed for NHL subtypes with longer duration of phenoxy herbicide use, such as for any phenoxy herbicide with multiple myeloma (>25.5 years, OR=1.78, 95% CI: 0.74 to 4.27), 2,4-D with diffuse large B-cell lymphoma (>25.5 years, OR=1.47, 95% CI: 0.67 to 3.21) and other (non-2,4-D) phenoxy herbicides with T-cell lymphoma (>6 years, lagged 10 years, OR=3.24, 95% CI: 1.03 to 10.2). An association between glyphosate and follicular lymphoma (lagged 10 years: OR=1.48, 95% CI: 0.98 to 2.25) was fairly consistent across analyses. CONCLUSIONS: Most of the herbicides examined were not associated with NHL risk. However, associations of phenoxy herbicides and glyphosate with particular NHL subtypes underscore the importance of estimating subtype-specific risks.

Risk perceptions and health care use in the era of the COVID-19 pandemic in adults treated for childhood cancer.

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.

Residential proximity to croplands at birth and childhood leukaemia.

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.

Occupational insecticide exposure and risk of non-Hodgkin lymphoma: A pooled case-control study from the InterLymph Consortium.

Evidence for the human health effects of pesticides is needed to inform risk assessment. We studied the relationship between occupational insecticide use and risk of non-Hodgkin lymphoma (NHL) by pooling data from nine case-control studies participating in the InterLymph Consortium, including 7909 cases and 8644 controls from North America, the European Union and Australia. Insecticide use was coded using self-report or expert assessment, for insecticide groups (eg, organophosphates, pyrethroids) and active ingredients (eg, malathion, permethrin). Associations with insecticides were estimated using logistic regression to produce odds ratios (ORs) and 95% confidence intervals (CI) for all NHL and NHL subtypes, with adjustment for study site, demographic factors and use of other pesticides. Occupational insecticide use, overall, was not associated with risk of NHL. Use of organophosphate insecticides was associated with increased risk of all NHL and the subtype follicular lymphoma, and an association was found with diazinon, in particular (ever use: OR = 2.05, 95%CI: 1.24-3.37). The carbamate insecticide, carbaryl, was associated with risk of all NHL, and the strongest associations were found with T-cell NHL for ever-use (OR = 2.44, 95%CI: 1.13-5.28) and longer duration (>8 years vs never: OR = 2.90, 95%CI: 1.02-8.25). There was no association of NHL with other broad groups of insecticides, including organochlorines and pyrethroids, and some inverse associations were estimated in relation to historical DDT use. Our findings contribute to the totality of evidence available to help inform risk decisions by public health and regulatory agencies of importance given continued, widespread use of organophosphate and carbamate insecticides.

Seasonal variations in childhood leukaemia incidence in France, 1990-2014.

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.

Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes.

Epidemiologic studies show an increased risk of non-Hodgkin lymphoma (NHL) in patients with autoimmune disease (AD), due to a combination of shared environmental factors and/or genetic factors, or a causative cascade: chronic inflammation/antigen-stimulation in one disease leads to another. Here we assess shared genetic risk in genome-wide-association-studies (GWAS). Secondary analysis of GWAS of NHL subtypes (chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and marginal zone lymphoma) and ADs (rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis). Shared genetic risk was assessed by (a) description of regional genetic of overlap, (b) polygenic risk score (PRS), (c)"diseasome", (d)meta-analysis. Descriptive analysis revealed few shared genetic factors between each AD and each NHL subtype. The PRS of ADs were not increased in NHL patients (nor vice versa). In the diseasome, NHLs shared more genetic etiology with ADs than solid cancers (p = .0041). A meta-analysis (combing AD with NHL) implicated genes of apoptosis and telomere length. This GWAS-based analysis four NHL subtypes and three ADs revealed few weakly-associated shared loci, explaining little total risk. This suggests common genetic variation, as assessed by GWAS in these sample sizes, may not be the primary explanation for the link between these ADs and NHLs.

Maternal and perinatal characteristics, congenital malformations and the risk of wilms tumor: the ESTELLE study.

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.

Association of polygenic risk score with the risk of chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis.

Inherited loci have been found to be associated with risk of chronic lymphocytic leukemia (CLL). A combined polygenic risk score (PRS) of representative single nucleotide polymorphisms (SNPs) from these loci may improve risk prediction over individual SNPs. Herein, we evaluated the association of a PRS with CLL risk and its precursor, monoclonal B-cell lymphocytosis (MBL). We assessed its validity and discriminative ability in an independent sample and evaluated effect modification and confounding by family history (FH) of hematological cancers. For discovery, we pooled genotype data on 41 representative SNPs from 1499 CLL and 2459 controls from the InterLymph Consortium. For validation, we used data from 1267 controls from Mayo Clinic and 201 CLL, 95 MBL, and 144 controls with a FH of CLL from the Genetic Epidemiology of CLL Consortium. We used odds ratios (ORs) to estimate disease associations with PRS and c-statistics to assess discriminatory accuracy. In InterLymph, the continuous PRS was strongly associated with CLL risk (OR, 2.49; P = 4.4 × 10-94). We replicated these findings in the Genetic Epidemiology of CLL Consortium and Mayo controls (OR, 3.02; P = 7.8 × 10-30) and observed high discrimination (c-statistic = 0.78). When jointly modeled with FH, PRS retained its significance, along with FH status. Finally, we found a highly significant association of the continuous PRS with MBL risk (OR, 2.81; P = 9.8 × 10-16). In conclusion, our validated PRS was strongly associated with CLL risk, adding information beyond FH. The PRS provides a means of identifying those individuals at greater risk for CLL as well as those at increased risk of MBL, a condition that has potential clinical impact beyond CLL.

Agricultural crop density in the municipalities of France and incidence of childhood leukemia: An ecological study.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. DISCUSSION: 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.

Parental smoking, maternal alcohol consumption during pregnancy and the risk of neuroblastoma in children. A pooled analysis of the ESCALE and ESTELLE French studies.

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.

Family history of cancer and the risk of childhood brain tumors: a pooled analysis of the ESCALE and ESTELLE studies (SFCE).

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.

Blood transfusion history and risk of non-Hodgkin lymphoma: an InterLymph pooled analysis.

PURPOSE: To conduct a pooled analysis assessing the association of blood transfusion with risk of non-Hodgkin lymphoma (NHL). METHODS: We used harmonized data from 13 case-control studies (10,805 cases, 14,026 controls) in the InterLymph Consortium. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression, adjusted for study design variables. RESULTS: Among non-Hispanic whites (NHW), history of any transfusion was inversely associated with NHL risk for men (OR 0.74; 95% CI 0.65-0.83) but not women (OR 0.92; 95% CI 0.83-1.03), pheterogeneity = 0.014. Transfusion history was not associated with risk in other racial/ethnic groups. There was no trend with the number of transfusions, time since first transfusion, age at first transfusion, or decade of first transfusion, and further adjustment for socioeconomic status, body mass index, smoking, alcohol use, and HCV seropositivity did not alter the results. Associations for NHW men were stronger in hospital-based (OR 0.56; 95% CI 0.45-0.70) but still apparent in population-based (OR 0.84; 95% CI 0.72-0.98) studies. CONCLUSIONS: In the setting of a literature reporting mainly null and some positive associations, and the lack of a clear methodologic explanation for our inverse association restricted to NHW men, the current body of evidence suggests that there is no association of blood transfusion with risk of NHL.

Parental occupational exposure to low-frequency magnetic fields and risk of leukaemia in the offspring: findings from the Childhood Leukaemia International Consortium (CLIC).

OBJECTIVES: Previously published studies on parental occupational exposure to extremely low-frequency magnetic fields (ELF-MF) and risk of acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML) in their offspring were inconsistent. We therefore evaluated this question within the Childhood Leukemia International Consortium. METHODS: We pooled 11 case-control studies including 9723 childhood leukaemia cases and 17 099 controls. Parental occupational ELF-MF exposure was estimated by linking jobs to an ELF-MF job-exposure matrix (JEM). Logistic regression models were used to estimate ORs and 95% CIs in pooled analyses and meta-analyses. RESULTS: ORs from pooled analyses for paternal ELF-MF exposure >0.2 microtesla (µT) at conception were 1.04 (95% CI 0.95 to 1.13) for ALL and 1.06 (95% CI 0.87 to 1.29) for AML, compared with ≤0.2 µT. Corresponding ORs for maternal ELF-MF exposure during pregnancy were 1.00 (95% CI 0.89 to 1.12) for ALL and 0.85 (95% CI 0.61 to 1.16) for AML. No trends of increasing ORs with increasing exposure level were evident. Furthermore, no associations were observed in the meta-analyses. CONCLUSIONS: In this large international dataset applying a comprehensive quantitative JEM, we did not find any associations between parental occupational ELF-MF exposure and childhood leukaemia.

Maternal residential pesticide use during pregnancy and risk of malignant childhood brain tumors: A pooled analysis of the ESCALE and ESTELLE studies (SFCE).

Some previous epidemiological studies have suggested that pesticide exposure during pregnancy may have a possible role in the development of childhood brain tumors (CBT). We pooled data from two French national population-based, case-control studies to investigate the association between maternal residential use of pesticides during pregnancy and the risk of CBT. The mothers of 437 CBT cases and 3,102 controls aged under 15 years who resided in France at diagnosis/interview, frequency-matched by age and gender, answered a structured telephone interview conducted by trained interviewers. Unconditional logistic regression was used to estimate pooled odds ratio (OR) and 95% confidence intervals (95% CI). CBT was significantly associated with the maternal home use of pesticides during pregnancy (OR 1.4, 95% CI 1.2-1.8) and, more specifically, with insecticide (OR 1.4, 1.2-1.8). We could not draw any conclusions about herbicides and/or fungicides because few women used them during pregnancy and most of these mothers also used insecticides. Although potential recall bias cannot be excluded, our findings of this pooled analysis support the hypothesis that residential maternal use of pesticides during pregnancy and particularly insecticides may increase the risk of CBT. Future investigations to verify these findings and to explore for CBT subtypes and dose-response are necessary to have a better understanding of the possible role of pesticides in etiology of CBT.