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.

Coffee and tea consumption during pregnancy and risk of childhood acute myeloid leukemia: A Childhood Leukemia International Consortium (CLIC) study.

BACKGROUND: Dietary habits during pregnancy have been inconsistently linked to childhood acute myeloid leukemia (AML), given the putative intrauterine onset of the disease as a result of triggering events during the critical period of fetal hematopoiesis. We investigated the potential association of maternal coffee and tea consumption during pregnancy with childhood AML risk, pooling primary data from eight case-control studies participating in the Childhood Leukemia International Consortium. METHODS: Information on coffee and/or tea consumption was available for 444 cases and 1255 age- and sex-matched controls, on coffee consumption for 318 cases and 971 controls and on tea consumption for 388 cases and 932 controls. Categories for cups of daily coffee/tea consumption were created in order to explore potential dose-response associations. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression. RESULTS: Associations were found neither in the analysis on coffee or tea nor in the analysis on coffee only consumption (any versus no). A positive association with increasing coffee intake was observed (>1 cup per day; OR: 1.40, 95% CI: 1.03-1.92, increment of one cup per day; OR: 1.18, 95% CI: 1.01-1.39). No associations were observed with tea consumption. Interaction analyses showed non-significant associations between coffee/tea and smoking. Hyperdiploidy was inversely associated with tea consumption, with other cytogenetic markers having no association with coffee/tea. CONCLUSION: Given the widespread consumption of caffeinated beverages among pregnant women, our finding is of important public health relevance, suggesting adverse effects of maternal coffee consumption during pregnancy in the offspring.

Maternal consumption of coffee and tea during pregnancy and risk of childhood ALL: a pooled analysis from the childhood Leukemia International Consortium.

PURPOSE: The early onset of childhood acute lymphoblastic leukemia (ALL) suggests that critical exposures occurring during pregnancy may increase risk. We investigated the effects of maternal coffee and tea consumption during pregnancy on ALL risk by pooling data from eight case-control studies participating in the Childhood Leukemia International Consortium. METHOD: Data on maternal coffee intake were available for 2,552 cases and 4,876 controls, and data on tea intake were available for 2,982 cases and 5,367 controls. Coffee and tea intake was categorized into 0, > 0-1, > 1-2, and > 2 cups/day, and covariates were combined and harmonized. Data on genetic variants in NAT2, CYP1A1, and NQO1 were also available in a subset. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression, and linear trends across categories were assessed. RESULTS: No association was seen with 'any' maternal coffee consumption during pregnancy, but there was evidence of a positive exposure-response; the pooled OR for > 2 cups/day versus none was 1.27 (95% CI 1.09-1.43), p trend = 0.005. No associations were observed with tea consumption. No interactions were seen between coffee or tea intake and age, maternal smoking or genotype, and there was little or no evidence that associations with coffee or tea differed among cases with and without chromosomal translocations. CONCLUSIONS: Despite some limitations, our findings suggest that high coffee intake during pregnancy may increase risk of childhood ALL. Thus, current advice to limit caffeine intake during pregnancy to reduce risk of preterm birth may have additional benefits.

Parental smoking, maternal alcohol, coffee and tea consumption and the risk of childhood brain tumours: the ESTELLE and ESCALE studies (SFCE, France).

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.

Factors related to pregnancy and birth and the risk of childhood brain tumours: The ESTELLE and ESCALE studies (SFCE, France).

Little is known of the causes of childhood brain tumors (CBT). The aims of this study were to investigate whether extremes of birth weight were associated with increased risk of CBT and whether maternal preconceptional folic acid supplementation or breastfeeding reduced the risk. In addition, other maternal characteristics and birth related factors were also investigated. 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 did a telephone interview, which focussed on demographic and perinatal characteristics, and maternal life style habits and reproductive history. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression, adjusted for age, sex, study of origin and relevant confounders. No association was found between CBT and birth weight or fetal growth. The use of preconceptional folic acid supplementation was rare (5.3% in cases and 7.8% in controls) and the OR was 0.8 (95% CI 0.5, 1.4). There was no association with breastfeeding, even prolonged (six months or more; OR 1.0, 95% CI 0.8, 1.4). Neither was there any association between CBT and other investigated factors (maternal body mass index, gestational weight gain, congenital abnormality, maternal reproductive history or use of fertility treatments. Although large, this study was underpowered for subtype analyses. Pooling data with other population-based studies may provide further insight into findings by CBT subtypes.

Risk of neuroblastoma, birth-related characteristics, congenital malformations and perinatal exposures: A pooled analysis of the ESCALE and ESTELLE French studies (SFCE).

Neuroblastoma (NB), an embryonic tumour arising from neural crest cells, is the most common malignancy among infants. The aetiology of NB is largely unknown. We conducted a pooled analysis to explore whether there is an association between NB and preconception and perinatal factors using data from two French national population-based case-control studies. The mothers of 357 NB cases and 1783 controls younger than 6 years, frequency-matched by age and gender, responded to a telephone interview that focused on demographic, socioeconomic and perinatal characteristics, childhood environment, life-style and maternal reproductive history. Unconditional logistic regression was used to estimate pooled odds ratios and 95% confidence intervals. After controlling for matching variables, study of origin and potential confounders, being born either small (OR 1.4 95% CI 1.0-2.0) or large (OR 1.5 95% CI 1.1-2.2) for gestational age and, among children younger than 18 months, having congenital malformations (OR 3.6 95% CI 1.3-8.9), were significantly associated with NB. Inverse associations were observed with breastfeeding (OR 0.7 95% CI 0.5-1.0) and maternal use of any supplements containing folic acid, vitamins or minerals (OR 0.5 95% CI 0.3-0.9) during the preconception period. Our findings reinforce the hypothesis that fetal growth anomalies and congenital malformations may be associated with an increased risk of NB. Further investigations are needed in order to clarify the role of folic acid supplementation and breastfeeding, given their potential importance in NB prevention.

Confirmation of childhood acute lymphoblastic leukemia variants, ARID5B and IKZF1, and interaction with parental environmental exposures.

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

Maternal reproductive history, fertility treatments and folic acid supplementation in the risk of childhood acute leukemia: the ESTELLE study.

PURPOSE: To investigate the potential involvement of fertility treatments and other conditions of becoming pregnant (infertility, getting pregnant on birth control, maternal history of fetal loss) and folic acid supplements in the etiology of childhood leukemia (CL). METHODS: The ESTELLE study included 747 cases of CL [636 cases of acute lymphoblastic leukemia (ALL) and 100 of acute myeloblastic leukemia (AML)] diagnosed in France in 2010-2011 and 1,421 population controls frequency-matched with the cases on age and gender. Data were obtained from structured telephone questionnaires administered to mothers. The odds ratios (OR) and their 95% confidence intervals were estimated using unconditional regression models adjusted for potential confounders. RESULTS: CL was not associated with difficulty in becoming pregnant [OR 0.9 (0.7-1.2)], in vitro fertilisation [OR 0.6 (0.3-1.5)] or the use of any fertility treatment [OR 0.8 (0.5-1.1)] for the index pregnancy. CL was not significantly associated with becoming pregnant on contraception [OR 1.2 (0.8-1.8)], but a positive association was observed for third generation oral contraception [OR 4.3 (1.2-16.2)]; however, the result is based on small numbers. Folic acid supplementation during pregnancy was not associated with CL, but an inverse borderline association was observed for supplementation initiated in the 3 months preceding pregnancy [OR 0.7 (0.5-1.0)]. In addition, maternal histories of stillbirth and miscarriage were associated with ALL [OR 2.6 (1.1-5.9)] and AML [OR 1.8 (1.1-2.8)], respectively. CONCLUSIONS: The findings do not suggest that infertility and fertility treatments are risk factors for CL. They suggest that maternal histories of stillbirth and miscarriage may be more frequent among mothers of CL cases and that folic acid supplementation during preconception may reduce the risk of CL.

Childhood acute leukemia, maternal beverage intake during pregnancy, and metabolic polymorphisms.

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.

Folic acid supplementation, MTHFR and MTRR polymorphisms, and the risk of childhood leukemia: the ESCALE study (SFCE).

PURPOSE: Fetal folate deficiency may increase the risk of subsequent childhood acute leukemia (AL), since folates are required for DNA methylation, synthesis, and repair, but the literature remains scarce. This study tested the hypothesis that maternal folic acid supplementation before or during pregnancy reduces AL risk, accounting for the SNPs rs1801133 (C677T) and rs1801131 (A1298C) in MTHFR and rs1801394 (A66G) and rs1532268 (C524T) in MTRR, assumed to modify folate metabolism. METHODS: The nationwide registry-based case-control study, ESCALE, carried out in 2003-2004, included 764 AL cases and 1,681 controls frequency matched with the cases on age and gender. Information on folic acid supplementation was obtained by standardized telephone interview. The genotypes were obtained using high-throughput platforms and imputation for untyped polymorphisms. Odds ratios (OR) were estimated using unconditional regression models adjusted for potential confounders. RESULTS: AL was significantly inversely associated with maternal folic acid supplementation before and during pregnancy (OR = 0.4; 95 % confidence interval: [0.3-0.6]). MTHFR and MTRR genetic polymorphisms were not associated with AL. However, AL was positively associated with homozygosity for any of the MTHFR polymorphisms and carriership of both MTRR variant alleles (OR = 1.6 [0.9-3.1]). No interaction was observed between MTHFR, MTRR, and maternal folate supplementation. CONCLUSION: The study findings support the hypothesis that maternal folic acid supplementation may reduce the risk of childhood AL. The findings also suggest that the genotype homozygous for any of the MTHFR variants and carrying both MTRR variants could be a risk factor for AL.