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

BACKGROUND: 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.

Childhood leukaemia close to high-voltage power lines--the Geocap study, 2002-2007.

BACKGROUND: High-voltage overhead power lines (HVOLs) are a source of extremely low-frequency magnetic fields (ELF-MFs), which are classified as possible risk factors for childhood acute leukaemia (AL). The study was carried out to test the hypothesis of an increased AL incidence in children living close to HVOL of 225-400 kV (VHV-HVOL) and 63-150 kV (HV-HVOL). METHODS: The nationwide Geocap study included all the 2779 cases of childhood AL diagnosed in France over 2002-2007 and 30 000 contemporaneous population controls. The addresses at the time of inclusion were geocoded and precisely located around the whole HVOL network. RESULTS: Increased odds ratios (ORs) were observed for AL occurrence and living within 50 m of a VHV-HVOL (OR=1.7 (0.9-3.6)). In contrast, there was no association with living beyond that distance from a VHV-HVOL or within 50 m of a HV-HVOL. CONCLUSION: The present study, free from any participation bias, supports the previous international findings of an increase in AL incidence close to VHV-HVOL. In order to investigate for a potential role of ELF-MF in the results, ELF-MF at the residences close to HVOL are to be estimated, using models based on the annual current loads and local characteristics of the lines.

Time trends and seasonal variations in the diagnosis of childhood acute lymphoblastic leukaemia in France.

BACKGROUND: Several studies have evidenced an increase in the incidence of childhood leukaemia since the 1970s but the variations since 2000 have received little attention. Seasonal variations in incidence have also been widely investigated, with however inconsistent conclusions. The present study aimed to investigate jointly the temporal trends and the seasonal variations in the month of diagnosis of childhood acute lymphoblastic leukaemia (ALL). METHODS: All the cases of ALL registered in the French National Registry of Childhood Haematological malignancies during 1990-2007 were included in the study. The overall temporal trend and seasonality of ALL were tested with Poisson regression models on 0-14-year-old ALL cases, and specifically on the B-cell precursor ALL (Bcp-ALL) cases. The analyses were also stratified by age groups and gender. RESULTS: Over 1990-2007, a significant time trend in risk of +0.48% (0.02-0.95%) per year for all ALL and +0.85% (0.33-1.37%) for Bcp-ALL was found. The increase was more marked for 7-14-year-old girls with a trend of +2.84% (1.34-4.36%) per year for Bcp-ALL. Seasonal variations were also evidenced for 1-6-year-old boys, with a standardised incidence ratio of 1.11 (1.04-1.18) for Bcp-ALL in April, August and December. CONCLUSION: The study showed an increase in childhood ALL risk over 1990-2007, which tended to be stronger for 7-14-year-old Bcp-ALL, particularly in girls (about one case per year, on average). However, although in accordance with the log-linear assumption, the increase in risk seemed less marked after 2001. The study also suggested seasonal variations in the month of diagnosis for 1-6-year-old boys.

Childhood leukaemia and population movements in France, 1990-2003.

In a national study, we investigated the incidence of childhood leukaemia (CL) over a 14-year period in France in relation to several measures based on the proportion of individuals who changed address between the last two national censuses. A positive association was found with the proportion of migrants who came from a distant place. The further the migrants came, the higher was the incidence of leukaemia, particularly among children aged 0-4 years in 'isolated' communes at the time of diagnosis (RR=1.4, 95% CI: 1.1,1.8 in the highest category of migration distance). Although the role of the population density was less obvious, a more marked association was found above a certain threshold. No association with the proportion of commuters was observed.

Population-mixing at the place of residence at the time of birth and incidence of childhood leukaemia in France.

The association between the risk of childhood leukaemia before age 7 years and population-mixing at the place of residence at birth was investigated by retrospectively considering all the children born in mainland French communes between 1st January 1990 and 31st December 1998. An increased risk of acute lymphoblastic leukaemia was found with higher levels of migration for children residing at birth in isolated communes with a population density > or =50 people per km2 (SIRR = 2.59, 95% CI: 1.48-4.49). No association was observed with lower population densities. For children residing in non-isolated communes at birth, the results were similar but less marked. The risk tended to increase only for population densities > or =5000 people per km2 (SIRR = 1.57, 95% CI: 0.99-2.52). The findings are consistent with epidemic models and support the hypothesis of an infectious aetiology relating to population-mixing. Population density may be seen as an indicator of the opportunity of contacts between inhabitants and should therefore be taken into account when investigating an infectious hypothesis. This is the first systematic study of population-mixing at the place of residence at the time of birth to be conducted on a national scale.

Excess mortality related to the August 2003 heat wave in France.

OBJECTIVES: From August 1st to 20th, 2003, the mean maximum temperature in France exceeded the seasonal norm by 11-12 degrees C on nine consecutive days. A major increase in mortality was then observed, which main epidemiological features are described herein. METHODS: The number of deaths observed from August to November 2003 in France was compared to those expected on the basis of the mortality rates observed from 2000 to 2002 and the 2003 population estimates. RESULTS: From August 1st to 20th, 2003, 15,000 excess deaths were observed. From 35 years age, the excess mortality was marked and increased with age. It was 15% higher in women than in men of comparable age as of age 45 years. Excess mortality at home and in retirement institutions was greater than that in hospitals. The mortality of widowed, single and divorced subjects was greater than that of married people. Deaths directly related to heat, heatstroke, hyperthermia and dehydration increased massively. Cardiovascular diseases, ill-defined morbid disorders, respiratory diseases and nervous system diseases also markedly contributed to the excess mortality. The geographic variations in mortality showed a clear age-dependent relationship with the number of very hot days. No harvesting effect was observed. CONCLUSIONS: Heat waves must be considered as a threat to European populations living in climates that are currently temperate. While the elderly and people living alone are particularly vulnerable to heat waves, no segment of the population may be considered protected from the risks associated with heat waves.

Spatial and space-time clustering of childhood acute leukaemia in France from 1990 to 2000: a nationwide study.

This study aimed to investigate the spatial and space-time distributions of cases of childhood acute leukaemia (CL) during 1990-2000 over the whole French territory. A global spatial heterogeneity and a spatial autocorrelation were first considered using the methods proposed by Potthoff and Whittinghill, Moran and Rogerson methods. The presence of space-time interaction between the places of residence and the dates of diagnosis was investigated with the Knox's test. Finally, the Kulldorff's statistic permitted to scan the whole territory in search for localised clusters. Two time periods were considered (1990-1994, 1995-2000). Overall, a statistically significant spatial heterogeneity of a very small magnitude was observed in the incidence of CL over 1990-1994, but neither over 1995-2000 nor over the whole time period. Moreover, a significant overdispersion of 5.5% was evidenced for 0-4 year children living in isolated areas with more than 50 inhabitants per km(2). Cases older than 10 years living in the same area at diagnosis also tended to cluster within 6 months.

Incidence of childhood leukaemia and non-Hodgkin's lymphoma in France: National Registry of Childhood Leukaemia and Lymphoma, 1990-1999.

The French National Registry of Childhood Leukaemia and Lymphoma (NRCL) covers the whole French mainland population aged less than 15 years (approximately 11 million children) for all childhood haematopoietic tumours since 1 January 1990, except Hodgkin's disease, which has been registered since 1 January 1999. During the period from 1990 to 1999, 5757 cases of leukaemia, lymphoma and myelodysplastic syndrome were registered in the NRCL, with an average of 2.5 sources per case. The age-standardized incidence rates per million per year were 43.1 for leukaemia (34.3 for acute lymphoblastic leukaemia, 7.1 for acute myeloblastic leukaemia, 0.6 for chronic myeloid leukaemia and 0.5 for chronic myelomonocytic leukaemia), 8.9 for non-Hodgkin's lymphomas and 6.7 for Hodgkin's disease. Down's syndrome was present in 110 cases of acute leukaemia (2.5%) and three cases of non-Hodgkin's lymphoma (0.3%). The incidence of acute lymphoblastic leukaemia showed a typical peak at age 2 years for girls and 3 years for boys. The incidence rates of leukaemia and non-Hodgkin's lymphoma did not show any temporal trends over the 10 year period.