Childhood acute lymphoblastic leukaemia and indicators of early immune stimulation: the Estelle study (SFCE).

BACKGROUND: Factors related to early stimulation of the immune system (breastfeeding, proxies for exposure to infectious agents, normal delivery, and exposure to animals in early life) have been suggested to decrease the risk of childhood acute lymphoblastic leukaemia (ALL). METHODS: The national registry-based case-control study, ESTELLE, was carried out in France in 2010-2011. Population controls were frequency matched with cases on age and gender. The participation rates were 93% for cases and 86% for controls. Data were obtained from structured telephone questionnaires administered to mothers. Odds ratios (OR) were estimated using unconditional regression models adjusted for age, gender, and potential confounders. RESULTS: In all, 617 ALL and 1225 controls aged ⩾1 year were included. Inverse associations between ALL and early common infections (OR=0.8, 95% confidence interval (CI): 0.6, 1.0), non-first born (⩾3 vs 1; OR=0.7, 95% CI: 0.5, 1.0), attendance of a day-care centre before age 1 year (OR=0.7, 95% CI: 0.5, 1.0), breastfeeding (OR=0.8, 95% CI: 0.7, 1.0), and regular contact with pets (OR=0.8, 95% CI: 0.7, 1.0) in infancy were observed. CONCLUSIONS: The results support the hypothesis that conditions promoting the maturation of the immune system in infancy have a protective role with respect to ALL.

Parental smoking, maternal alcohol, coffee and tea consumption during pregnancy, and childhood acute leukemia: the ESTELLE study.

PURPOSE: To investigate the role of parental smoking during pre-conception and pregnancy, maternal beverage consumption (alcohol, coffee and tea) during pregnancy and their possible interactions, in the etiology of childhood acute leukemia (CL). METHODS: The ESTELLE study included 747 cases of CL [636 cases of acute lymphoblastic leukemia (ALL) and 100 cases 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 the mothers. The odds ratios (OR) and their 95 % confidence intervals were estimated using unconditional logistic regression models adjusted for potential confounders. RESULTS: AML, but not ALL, was non-significantly associated with alcohol drinking during pregnancy [OR = 1.3 (0.8-2.0)] with a significant positive dose-response trend (p-trend = 0.02). Pre-conception paternal smoking was significantly associated with ALL [OR = 1.2 (1.1-1.5)] and AML [OR = 1.5 (1.0-2.3)]. CL was not associated with maternal smoking [OR = 1.0 (0.8-1.2)], or maternal coffee [OR = 0.9 (0.8-1.1)] or tea drinking [OR = 0.9 (0.8-1.1)] during pregnancy. However, a high consumption of coffee (>2 cups/day) was significantly associated with ALL [OR = 1.3 (1.0-1.8)]. CONCLUSIONS: The findings constitute additional evidence that maternal alcohol drinking during pregnancy may be involved in AML, and that paternal smoking before pregnancy may be a risk factor for CL. The role of maternal coffee drinking in CL remains unclear and should be investigated further in consortium analyses and in large birth cohort studies with exposure assessment more contemporaneous with the exposure, before the occurrence of the disease.

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.

Mechanisms of transcription in nucleoli of amphibian oocytes as visualized by high-resolution autoradiography.

In oocytes of Pleurodeles waltlii, the method of Miller and Beatty has been combined with a method of high-resolution autoradiography especially suitable for the study of isolated molecules. In vitro labeling of RNA by tritiated precursors was carried out with increasing incubation times (1, 4, 15, 24, 48, and 72 h). Silver grains were present over ribonucleoprotein fibrils in amounts sufficient for quantitative analysis of nucleolar DNA transcription. Statistical analysis of the data revealed that: (a) The units of any one nucleolus exhibited a large degree of heterogeneity in their number of grains. (b) There was a parallelism between the increasing grain number and the ribonucleoprotein-fibril lengthening as observed along the transcription unit.

Occupational exposure to pesticides and lymphoid neoplasms among men: results of a French case-control study.

OBJECTIVES: Investigating the relationship between occupational exposure to pesticides and the risk of lymphoid neoplasms (LNs) in men. METHODS: A hospital-based case-control study was conducted in six centres in France between 2000 and 2004. The cases were incident cases with a diagnosis of LN aged 18-75 years. During the same period, controls of the same age and sex as the cases were recruited in the same hospital, mainly in the orthopaedic and rheumatological departments. Exposures to pesticides were evaluated through specific interviews and case-by-case expert reviews. Four hundred and ninety-one cases (244 cases of non-Hodgkin's lymphoma (NHL), 87 of Hodgkin's lymphoma (HL), 104 of lymphoproliferative syndromes (LPSs) and 56 of multiple myeloma (MM) cases) and 456 controls were included in the analyses. The odds ratios (ORs) and 95% CI were estimated using unconditional logistic regressions. RESULTS: Positive associations between HL and occupational exposure to triazole fungicides and urea herbicides were observed (OR = 8.4 (2.2 to 32.4), 10.8 (2.4 to 48.1), respectively). Exposure to insecticides, fungicides and herbicides were linked to a threefold increase in MM risk (OR = 2.8 (1.2 to 6.5), 3.2 (1.4 to 7.2), 2.9 (1.3 to 6.5)). For LPS subtypes, associations restricted to hairy-cell leukaemia (HCL) were evidenced for exposure to organochlorine insecticides, phenoxy herbicides and triazine herbicides (OR = 4.9 (1.1 to 21.2), 4.1 (1.1 to 15.5), 5.1 (1.4 to 19.3)), although based on small numbers. Lastly, despite the increased ORs for organochlorine and organophosphate insecticides, carbamate fungicides and triazine herbicides, no significant associations were evidenced for NHL. CONCLUSIONS: The results, based on case-by-case expert review of occupation-specific questionnaires, support the hypothesis that occupational pesticide exposures may be involved in HL, MM and HCL and do not rule out a role in NHL. The analyses identified specific pesticides that deserve further investigation and the findings were consistent with those of previous studies.

Lung cancer mortality and iron oxide exposure in a French steel-producing factory.

OBJECTIVE: To study the possible association between iron oxide exposures and lung cancer risk among workers in a French carbon steel-producing factory. METHODS: 16 742 males and 959 females ever employed for at least 1 year between 1959 and 1997 were followed up for mortality from January 1968 to December 1998. Causes of death were ascertained from death certificates. Job histories and smoking habits were available for 99.7% and 72.3% of subjects, respectively. Occupational exposures were assessed by a factory-specific job-exposure matrix (JEM) validated with atmospheric measurements. Standardised mortality ratios (SMRs) were computed using local death rates (external references). Poisson regressions were used to estimate the relative risks (RRs) for occupational exposures (internal references), adjusted on potential confounding factors. RESULTS: Among males, observed mortality was lower than expected for lung cancer compared to the local population (233 deaths, SMR 0.89, 95% CI 0.78 to 1.01) and higher than expected compared to the French population (SMR 1.30, 95% CI 1.15 to 1.48) No lung cancer excess was observed for exposure to iron oxides (RR 0.80, 95% CI 0.55 to 1.17) and no dose-response relationship with intensity, duration of exposure or cumulative index was found. A significant bladder cancer excess was observed among workers exposed to oil mist (RR 2.44, 95% CI 1.06 to 5.60), increasing significantly with intensity, duration of exposure and cumulative index. CONCLUSION: This study did not detect any relationship between exposure to iron oxides and lung cancer mortality. An excess of mortality from bladder cancer was found among workers exposed to oil mist.

Acute childhood leukaemia and residence next to petrol stations and automotive repair garages: the ESCALE study (SFCE).

BACKGROUND: The association between acute childhood leukaemia and residing next to petrol stations and automotive repair garages was analysed in a national registry-based case-control study carried out in France in 2003-2004. METHODS: Population controls were frequency matched with cases on age and gender. Data were collected by standardised telephone interview with the mothers. The latter were asked to report the proximity of their homes to petrol stations, automotive repair garages and other businesses from the conception of the index child to the diagnosis (for cases) or interview (for controls). Odds ratios were estimated using unconditional regression models adjusted for age, gender, number of children under 15 years of age in the household, degree of urbanisation and type of housing. RESULTS: 765 cases of acute leukaemia and 1681 controls were included. Acute leukaemia was significantly associated with residence next to petrol stations or automotive repair garages (OR 1.6, 95% CI 1.2 to 2.2) and next to a petrol station (OR 1.9, 95% CI 1.2 to 3.0). The OR showed no tendency to increase with duration of exposure. The results were not modified by adjustment for potential confounding factors including urban/rural status and type of housing. CONCLUSIONS: The results support the findings of our previous study and suggest that living next to a petrol station may be associated with acute childhood leukaemia. The results also suggest that the role of low-level exposure to benzene in acute childhood leukaemia deserves further evaluation.

Cigarette smoking, alcohol drinking, and risk of lymphoid neoplasms: results of a French case-control study.

OBJECTIVE: To study potential role of smoking and alcohol in lymphoid neoplasms (LN). METHODS: A case-control study that included 824 cases and 752 hospital controls aged 18-75 years was conducted. Cases were newly diagnosed with non-Hodgkin's or Hodgkin's lymphoma, multiple myeloma, or lymphoproliferative syndrome (LPS). Controls were matched with the cases by gender, age, and center. RESULTS: Overall, smoking was not related to LN. However, average tobacco consumption tended to be inversely related to non-Hodgkin's lymphoma (NHL), LPS, and the hairy cell leukemia (HCL) subtype, with a significant negative trend for the latter (OR of 0.4, 0.2, 0.1 for consumptions of 20 cig/day). An inverse association between 'ever drinking' and Hodgkin's lymphoma (HL: OR = 0.5 [0.3-0.8]) and NHL (OR = 0.7 [0.5-1.0]) was evidenced and restricted to the diffuse large B-cell lymphoma subtype, with significant negative trends. The controls' smoking and drinking habits were similar to those of French population. The results remained unchanged after adjustment for potential confounding factors and when smoking and drinking were both included in the models. CONCLUSION: Results are consistent with those of several previous studies and suggest a direct or indirect protective effect of smoking with respect to HCL although based on small numbers. The negative relationship between alcohol consumption and Hodgkin's and NHL, also previously reported, needs further investigations.

Response to comment on "Indoor terrestrial gamma dose rate mapping in France: A case study using two different geostatistical models" by Warnery et al.

Elements to answer the points raised in the Letter in question are proposed, notably about exposure metrics and their influence on the results and statistical power of epidemiological studies.

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.

UDP-glucuronosyltransferase UGT1A7 genetic polymorphisms in hepatocellular carcinoma: a differential impact according to seropositivity of HBV or HCV markers?

BACKGROUND: We conducted a case-control study to evaluate the role of UDP-glucuronosyltransferase 1A7 (UGT1A7) polymorphisms in the onset of hepatocellular carcinoma (HCC). METHODS: The study included 165 patients with HCC, 134 with cirrhosis and 142 controls without liver disease, matched for age and hospital. All were men younger than 75 years. HCC and cirrhosis patients were stratified according to time since cirrhosis diagnosis. RESULTS: We found a positive association between the UGT1A7*3/*3 genotype and HCC when the comparison was restricted to patients whose disease was of viral origin [OR = 3.4 (0.3-45)] but a negative association when it included only alcoholic patients [OR = 0.1 (0.02-0.6), p = 0.01]. CONCLUSION: Our study shows that UGT1A7 may play a role in hepatocellular carcinogenesis and that this role may differ according to the primary cause of the cirrhosis.

Survival in France after childhood acute leukaemia and non-Hodgkin's lymphoma (1990-2000).

This article describes the survival after childhood acute leukaemia (AL) and non-Hodgkin's lymphoma (NHL) of French population aged less than 15 years. The French National Registry of Childhood Leukaemia and Lymphoma recorded 3995 cases of acute lymphoblastic leukaemia (ALL), 812 of acute myeloid leukaemia (AML) and 1137 of NHL over the period from 1990 to 2000. Overall survival rates at 5 years were 82% (95% CI 80-83), 58% (95% CI 54-61) and 87% (95% CI 85-89) for ALL, AML and NHL, respectively. Survival after AL increased from 77% (95% CI 75-80) in 1990-1992 to 85% (95% CI 83-87) in 1997-2000 for ALL and from 47% (95% CI 41-54) to 61% (95% CI 55-67) for AML. Among AL cases, children aged 1-4 years had the most favourable prognosis. Down's syndrome was associated with poor survival after ALL. No gender-related variations in survival were in evidence. The results reported herein are similar to those reported by other European registries and clinical trials.

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.

Household exposure to pesticides and risk of childhood acute leukaemia.

OBJECTIVES: To investigate the relation between childhood acute leukaemia and household exposure to pesticides. METHODS: The study included 280 incident cases of acute leukaemia and 288 controls frequency matched on gender, age, hospital, and ethnic origin. The data were obtained from standardised face to face interviews of the mothers with detailed questions on parental occupational history, home and garden insecticide use, and insecticidal treatment of pediculosis. Odds ratios were estimated using unconditional regression models including the stratification variables parental socioeconomic status and housing characteristics. RESULTS: Acute leukaemia was observed to be significantly associated with maternal home insecticide use during pregnancy (OR = 1.8, 95% CI 1.2 to 2.8) and during childhood (OR = 1.7, 95% CI 1.1 to 2.4), with garden insecticide use (OR = 2.4, 95% CI 1.3 to 4.3), and fungicide use (OR = 2.5, 95% CI 1.0 to 6.2) during childhood. Insecticidal shampoo treatment of pediculosis was also associated with childhood acute leukaemia (OR = 1.9, 95% CI 1.2 to 3.3). CONCLUSION: The results reported herein support the hypothesis that various types of insecticide exposure may be a risk factor for childhood acute leukaemia. The observed association with insecticidal shampoo treatment of pediculosis, which has never been investigated before, requires further study.

Ecological association between indoor radon concentration and childhood leukaemia incidence in France, 1990-1998.

The objective of this study was to evaluate the ecological association between indoor radon concentration and acute leukaemia incidence among children under 15 years of age in the 348 geographical units (zones d'emploi, ZE) of France between 1990 and 1998. During that period, 4015 cases were registered by the French National Registry of Childhood Leukaemia and Lymphoma. Exposure assessment was based on a campaign of 13 240 measurements covering the whole country. The arithmetic mean radon concentration was 85 Bq/m (range, 15-387 Bq/m) and the geometric mean, 59 Bq/m (range: 13-228 Bq/m). A positive ecological association, on the borderline of statistical significance (P=0.053), was observed between indoor radon concentration and childhood leukaemia incidence. The association was highly significant for acute myeloid leukaemia (AML) (P=0.004) but not for acute lymphocytic leukaemia (ALL) (P=0.49). The standardized incidence ratio (SIR) increased by 7, 3 and 24% for all acute leukaemia, ALL and AML, respectively, when radon concentration increased by 100 Bq/m. In conclusion, the present ecological study supports the hypothesis of a moderate association between indoor radon concentration and childhood acute myeloid leukaemia. It is consistent with most previous ecological studies. Since the association is moderate, this result does not appear inconsistent with the five published case-control studies, most of which found no significant association.

Relation between inducibility of CYP1A1, GSTM1 and lung cancer in a French population.

Smoking is the principal cause of lung cancer. However, not all smokers will develop this disease. Individual susceptibility to chemically induced cancer may be explained in part by genetic differences in the activation and detoxification of procarcinogens. The activation phase of polycyclic aromatic hydrocarbon (PAH) metabolism is governed by the enzyme CYP1A1, induced by PAH when it enters the body. The extent to which PAH induces CYP1A1 activity varies greatly from one subject to another. CYP1A1 inducibility has long been associated, although inconsistently, with an increased risk of lung cancer. In 1982, Kouri corroborated Kellerman's results with a new method for measuring inducibility, but few studies have reported using this method. The glutathione S-transferases (GSTs) are involved in the detoxification phase of PAH, and the allelic deletion of GSTM1 has been also associated with an increased risk of lung cancer. We conducted a case-control study to examine the risk of lung cancer related, separately and together, to CYP1A1 inducibility, GSTM1 polymorphism and cigarette smoking in a French population. The 611 subjects were 310 incident lung cancer cases and 301 hospital control subjects. We were able to constitute a DNA bank for 552 subjects (89.5%) and gather detailed information on smoking history for all of them. Inducibility could be measured for 195 cases and 183 control subjects. Results for GSTM1 polymorphism concern 247 cases and 254 control subjects. GSTM1 polymorphism and inducibility could both be assessed for 179 cases and 166 control subjects. The odds ratio related to inducibility was 1.7 [1.0-3.0] for medium and 3.1 (1.3-7.4) for hyper inducers. The association with GSTM1 was 1.6 (1.0-2.6). With a reference category of subjects who were both low inducers and GSTM1(+), we found an odds ratio for lung cancer of 8.1 (2-31) for the subjects with both risk factors [i.e. GSTM1(-) and hyper inducers]. Our data did not reveal evidence of interaction between smoking and inducibility. On the other hand, we found an interaction of 3.6 (0.6-21) between inducibility and GSTM1.

Genetic polymorphisms of cytochrome P450 2A6 in a case-control study on lung cancer in a French population.

Cytochrome P450 2A6 (CYP2A6) is involved in the C-oxidation of nicotine and in the metabolic activation of tobacco nitrosamines. Recent data have suggested that CYP2A6 genetic polymorphisms might play a role in tobacco dependence and consumption as well as in lung cancer risk. However, the previously published studies were based on a genotyping method that overestimated the frequencies of deficient alleles, leading to misclassification for the CYP2A6 genotype. In this study, we genotyped DNA from 244 lung cancer patients and from 250 control subjects for CYP2A6 (wild-type allele CYP2A6*1, and two deficient alleles: CYP2A6*2, and CYP2A6*4, the latter corresponding to a deletion of the gene) using a more specific procedure. In this Caucasian population, we found neither a relation between genetically impaired nicotine metabolism and cigarette consumption, nor any modification of lung cancer risk related to the presence of defective CYP2A6 alleles (odds ratio = 1.1, 95% confidence interval = 0.7-1.9).

Retrospective evaluation of occupational exposures in population-based case-control studies: general overview with special attention to job exposure matrices.

Different approaches may be considered in the evaluation of past occupational exposures: questionnaires only, questionnaires and experts (such as industrial hygienists or occupational physicians), questionnaires and job exposure matrices (JEM). These approaches are described in this paper and their use in the framework of population-based case-control studies is discussed. The use of experts to assess exposure from questionnaires is generally considered to be the reference method. Its major drawbacks are its cost and the shortage of experienced experts. On the other hand, JEM reduce the cost of the study and provide an objective way of evaluating exposures. The main drawback of JEM is the fact that they can produce misclassification. The development of a JEM includes the choice of the job classification system which influences the degree to which the matrix can be used in other studies, the precise definition of exposures, and the choice of entries which provide more information than the oversimplified exposed/non-exposed dichotomy. Recent results on JEM methodology (statistical methods of analysis and evaluation of JEM quality) should encourage both their development and their use in epidemiological studies.