Childhood leukemia around French nuclear power plants - The Geocap study, 2002-2007

International audienceThe 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) 5 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. © 2012 UICC

Childhood leukemia around French nuclear power plants The geocap study, 2002-2007. Responses to letters

International audience[No abstract available

Genetic polymorphisms of Th2 interleukins, history of asthma or eczema and childhood acute lymphoid leukaemia: Findings from the ESCALE study (SFCE)

International audienceBACKGROUND:Previous studies on the putative role of allergy in the aetiology of childhood leukaemia have reported contradictory results. The present study aimed to analyse the relation between a medical history of asthma or eczema and childhood acute lymphoid leukaemia (ALL) in light of potential candidate gene-environment interactions.METHODS:Analyses were based on a subset of 434 cases of ALL and 442 controls successfully genotyped and of European ancestry children enrolled in a French population-based case-control study conducted in 2003-2004. Information about medical history was obtained during a standardized interview with the mothers. Candidate polymorphisms in genes of the Th2 cytokines IL4, IL10, IL13 and IL4-receptor, were genotyped or imputed.RESULTS:None of the variant alleles were directly associated with childhood acute lymphoid leukaemia. A medical history of asthma or eczema was reported more often in the control group (OR = 0.7 [0.5-1.0]). This association was mostly seen in the group of children not carrying the IL13-rs20541 variant allele (Interaction Odds Ratio IOR 1.9, p-interaction = 0.07) and in those carrying the IL10 triple variant haplotype (IOR 0.5, p-interaction = 0.04). No interaction was observed with the candidate polymorphisms in IL4 and IL4R.CONCLUSION:This study provides a new insight into the relationship between allergic symptoms and childhood acute lymphoid leukaemia, by suggesting this inverse association could be limited to children carrying certain genetic polymorphisms. If confirmed, these results could help better understand the biological mechanisms involved in the development of childhood acute lymphoid leukaemia

Genetic polymorphisms and childhood acute lymphoblastic leukemia: GWAS of the ESCALE study (SFCE)

Every year, acute lymphoblastic leukaemia (ALL) affects about 400 children aged <15 years in France, accounting for approximately 80% of the acute leukaemia (AL) cases. The heterogeneity of cell types is reflected in the heterogeneity of clinical presentation, prognosis and, possibly, risk factors. In addition to Down’s syndrome, a few inheritable predisposing diseases and high-dose ionizing radiations increase the risk of ALL. Some environmental, infectious and genetic factors are consistently suspected. The first ALL genome-wide association studies (GWAS) reported clear associations between ALL and single-nucleotide polymorphisms (SNPs) flanking the Ikaros family zinc finger 1 gene (IKZF1) in 7p12.2 (rs6964823, rs4132601, rs6944602 or rs11978267), and the AT-rich interactive domain 5b gene (ARID5B) in 10q21.2 (rs7073837, rs10740055, rs7089424,3 or rs10821936, rs10994982. The latter association was more pronounced for hyperdiploid ALL in both GWAS. In the UK study, the SNP rs2239633 in the CCAAT/enhancer-binding protein epsilon gene (CEBPE) was also associated with ALL. Sherbone et al.5 analysed a subset of 34 SNPs selected in the UK GWAS3 and reported an association with rs3731217 in the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene. In addition, in a recent GWAS, four additional SNPs were associated with TEL-AML1-positive ALL (rs17505102 (TP63), rs1945213 (OR8U8), rs920590 (INTS10) and rs3942852 (PTPRJ)),6 requiring further investigation. We report the results of a GWAS conducted on the ALL cases from the ESCALE (Etude Sur les Cancers et les Leucémies de l’Enfant) nationwide registry-based study and generic controls. In addition, the SNPs associated with AL in the previous GWAS were considered in the ESCALE case–control study