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International audience; 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.

International audience; The increase in the thyroid cancer incidence in France observed over the last 20 years has raised public concern about its association with the 1986 nuclear power plant accident at Chernobyl. At the request of French authorities, a first study sought to quantify the possible risk of thyroid cancer associated with the Chernobyl fallout in France. This study suffered from two limitations. The first involved the lack of knowledge of spontaneous thyroid cancer incidence rates (in the absence of exposure), which was especially necessary to take their trends into account for projections over time; the second was the failure to consider the uncertainties. The aim of this article is to enhance the initial thyroid cancer risk assessment for the period 1991-2007 in the area of France most exposed to the fallout (i.e., eastern France) and thereby mitigate these limitations. We consider the changes over time in the incidence of spontaneous thyroid cancer and conduct both uncertainty and sensitivity analyses. The number of spontaneous thyroid cancers was estimated from French cancer registries on the basis of two scenarios: one with a constant incidence, the other using the trend observed. Thyroid doses were estimated from all available data about contamination in France from Chernobyl fallout. Results from a 1995 pooled analysis published by Ron et al. were used to determine the dose-response relation. Depending on the scenario, the number of spontaneous thyroid cancer cases ranges from 894 (90% CI: 869-920) to 1,716 (90% CI: 1,691-1,741). The number of excess thyroid cancer cases predicted ranges from 5 (90% UI: 1-15) to 63 (90% UI: 12-180). All of the assumptions underlying the thyroid cancer risk assessment are discussed.

International audience; INTRODUCTION: We investigated the role of maternal alcohol and coffee drinking and parental smoking on the risk of childhood acute leukemia in a multicenter case-control study. METHODS: The study included 280 incident cases and 288 hospitalized controls, frequency matched with the cases by age, gender and center. Data collection was completed by face-to-face standardized interviews of the case and control mothers. RESULTS: An association with maternal alcohol consumption during pregnancy was observed with acute lymphoid leukemia (ALL) (OR=2.0 [1.4-3.0]) and acute non-lymphoid leukemia (ANLL) (OR=2.6 [1.2-5.8]). Maternal coffee consumption during pregnancy was associated with childhood acute leukemia, ORs increasing in ALL with coffee consumption (OR=1.1 [0.7-1.8], OR=2.4 [1.3-4.7] and OR=3.1 [1.0-9.5], respectively, for < or =3, 4-8 and >8 cups/day). No association with maternal smoking during pregnancy or parental smoking before or after the index child's birth was observed. DISCUSSION: Our results suggest an association with maternal alcohol and coffee drinking during pregnancy and call for further investigations. Besides, the present study does not support the hypothesis of an increase in the risk of childhood leukemia related to parental smoking.

The objective of the present study was to investigate the role of early common infections and perinatal characteristics in the aetiology of childhood common leukaemia. A case-control study was conducted from 1995 to 1998 in France, and included 473 incident cases of acute leukaemia (AL) (408 acute lymphoblastic leukaemia (ALL), 65 acute myeloid leukaemia (AML) age-, sex- and region-matched with 567 population-based controls. Data on the medical history of the child and his/her environment were collected using self-administered questionnaires. Analyses were conducted using nonconditional logistic regression. A slight negative association with early infections was observed (OR=0.8; 95% CI (0.6-1.0)). The association was stronger for early gastrointestinal infections. Early day-care was found to be associated with a decreased risk of AL (OR=0.6; 95% CI (0.4-0.8) and OR=0.8; 95% CI (0.5-1.2) for day-care starting before age 3 months and between 3 and 6 months, respectively). No association with breast-feeding was observed, irrespective of its duration. A birth order of 4 or more was associated with a significantly increased risk of AL (OR=2.0; 95% CI (1.1-3.7) with ALL). A history of asthma was associated with a decreased risk of ALL (OR 0.5; 95% CI (0.3-0.90). Although the results regarding birth order and breast-feeding do not fit with Greaves' hypothesis, the study supports the hypothesis that early common infections may play a protective role in the aetiology of childhood leukaemia, although this effect was not more marked for common ALL.

La leucémie est un cancer qui atteint les cellules souches sanguines. La fréquence des leucémies est relativement faible mais, chez l’enfant, c’est le type de cancer le plus fréquent. Le développement de la maladie est multi-étapes ; depuis vingt ans, les preuves d’une initiation prénatale des leucémies aiguës de l’enfant se sont accumulées. Les facteurs qui induisent la formation d’une cellule leucémique sont vraisemblablement multiples : facteurs génétiques et/ou environnementaux. Très peu d’entre eux sont établis comme facteurs de risque certains. La découverte récente des polymorphismes liés au risque de leucémies aiguës de l’enfant modifie profondément le champ de la recherche sur les causes de ces maladies. Certains des facteurs de risque environnementaux suspectés pourraient modifier l'effet de ces gènes, et inversement, ces gènes pourraient influer sur l'effet de ces facteurs environnementaux au niveau de l'organisme.

Au cours du mois de juillet 2006, une vague de chaleur a touché une grande partie de la Francemétropolitaine durant 18 jours entre le 11 et le 28 juillet. Selon Météo-France, elle se situe au deuxième rangdes vagues de chaleur les plus sévères observées en France depuis 1950, après la vague d’août 2003. Lacanicule de 2006 dépasse en durée celle de 2003, mais est en revanche moins intense et moins étenduegéographiquement.A la suite de la vague de chaleur d’août 2003, des mesures de prévention des risques liés aux chaleurs estivalesexcessives et un système de surveillance et d’alerte des vagues de chaleur par l’Institut de Veille Sanitaire encollaboration avec Météo-France ont été mis en place depuis l’été 2004 afin de réduire la vulnérabilité de lapopulation aux températures extrêmes en été.Dans ce contexte, le présent rapport a pour objet :- de vérifier si le lien entre chaleur et mortalité observé de 1975 à 2003 rendait également bien compte desobservations sur la période 2004-2006, en comparant les nombres quotidiens de décès observés pendant lesétés 2004 à 2006 et les estimations des nombres attendus de décès élaborées à partir de la modélisation desobservations 1975-2003,- de quantifier plus spécifiquement la surmortalité que l’on aurait pu observer en juillet 2006, si le lien entre latempérature et la mortalité avait été identique à celui observé sur la période 1975-2003 et de comparer cettesurmortalité attendue à la surmortalité effectivement observée.Un modèle mettant en relation les fluctuations quotidiennes de la mortalité et celles des températures surles quatre mois d’été de juin à septembre, a été établi sur une période de 28 ans de 1975 à 2002. Il permetde fournir une mesure quantitative du nombre de décès attendu un jour donné, compte tenu des températuresobservées ce jour et les 10 jours précédents. Le niveau moyen de la mortalité de chaque été est ajusté sur celuides mois qui précèdent l’été et dont la mortalité est stable d’une année sur l’autre. Ce modèle permet de prédirele ratio de mortalité un jour donné à partir des températures observées ce jour et les 10 précédents avec unecorrélation linéaire r = + 0,88 avec les ratios quotidiens de décès observés. Il explique 76% de la variabilité extrapoissonniennedes taux de mortalité quotidiens observés au cours des 28 étés de 1975 à 2002 et permet deprédire de façon satisfaisante les observations de l’été 2003 (...)

International audience; 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.

Background Case reports and epidemiological studies have suggested a relationship between congenital anomalies and childhood cancer, but some potential associations remain inconsistent. In this study, we investigated the association between congenital anomalies and neuroblastoma. Procedure We used data of a case-control study on neuroblastoma conducted from 1992 to 1994, including 538 children aged 0–19 years with newly diagnosed, histologically confirmed neuroblastoma and 504 controls identified by telephone random-digit dialing and matched to cases on date of birth. Information on congenital anomalies and potential confounding factors was collected through maternal telephone interviews using a structured questionnaire. We estimated odds ratios (OR) and 95% confidence intervals (CI), adjusted for reference age at diagnosis, mother's educational level, mother's race, and household income at birth. Results An association between the maternal report of any congenital anomalies and neuroblastoma (OR = 2.58; CI = 1.57–4.25) was observed. Neuroblastoma risk increased with increasing number of anomalies per child (OR = 3.90, CI = 1.27–11.9 for two anomalies or more), and when we restricted analyses to major anomalies (OR = 7.53, CI = 2.23–25.5). Genitourinary anomalies (OR = 5.84, CI = 1.67–20.4) and cardiac anomalies (OR = 4.27, CI = 1.22–15.0) had an elevated, but imprecise neuroblastoma risk. Conclusions Our findings support the hypothesis of an association between neuroblastoma and congenital, especially urogenital and cardiac, anomalies. © 2004 Wiley-Liss, Inc.

International audience; Exceptionally high incidence rates of thyroid cancer have been reported for Melanesian women in New Caledonia (South Pacific). To investigate the occurrence of thyroid cancer in that country and to clarify the role of goiter and hormonal factors in that disease in women, a countrywide population-based case-control study was conducted in 1993-1999. The study included 293 cases, identified through pathology registers and whose thyroid cancer was verified histologically, and 354 population controls. Thyroid cancer was associated with goiter, age at menarche, irregular menstruation, and hysterectomy. There was a dose-response trend with number of full-term pregnancies (p = 0.01), with an odds ratio of 2.2 (95% confidence interval: 1.1, 4.3) for women with eight or more pregnancies. Miscarriage, particularly as an outcome of the first pregnancy, was also indicated as a risk factor. The association between voluntary abortion and thyroid microcarcinoma could be explained by enhanced medical surveillance and improved cancer detection in women undergoing abortion. Oral contraceptives and hormone replacement therapy were unrelated to thyroid cancer. The very high birth rate among Melanesian women in New Caledonia, as well as late age at menarche, may explain, in part, their elevated incidence of thyroid cancer.

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.

International audience; OBJECTIVE: Uveal melanoma is a rare disease with poor prognosis and largely unknown etiology. We studied potential occupational risk factors. METHODS: A population based case-control study was undertaken during 1995-1997 in nine European countries using population and colon cancer controls with personal interviews. Occupational exposure to sunlight and artificial UV radiation was assessed with a job exposure matrix. In total, 320 uveal melanoma cases were eligible at pathology review, and 292 cases were interviewed, participation 91%. Out of 3357 population controls, 2062 were interviewed, 61%, and out of 1272 cancer controls 1094 were interviewed, 86%. RESULTS: Using population controls, occupational exposure to sunlight was not associated with an increased risk (RR=1.24, 95% CI=0.88-1.74), while an excess risk found with use of colon cancer controls was attributed to confounding factors. An excess risk in welders was restricted to the French part of the data. Cooks, RR=2.40; cleaners, RR 2.15; and laundry workers, RR=3.14, were at increased risk of uveal melanoma. CONCLUSION: Our study does overall not support an association between occupational sunlight exposure and risk of uveal melanoma. The finding of an excess risk of eye melanoma in cooks in several European countries is intriguing.

International audience; Metabolic polymorphisms may influence the risk of childhood leukaemia related to maternal tobacco, coffee or alcohol consumption. The data were extracted from a case-control study including 280 cases of acute leukaemia and 288 controls. Blood sampling was obtained for a representative subset of 219 cases and 105 controls. Gene-environment interactions were estimated using both case-control and case-only analyses. The polymorphisms of CYP1A1, GSTM1, GSTP1, GSTT1 and NQO1 were not associated with the risk of leukaemia. The slow EPHX1 allele was negatively associated with childhood leukaemia while an inverse non-significant association was observed with the fast EPHX1 allele. Maternal smoking during pregnancy was not related to leukaemia, but an interaction was observed in the case-only analysis with CYP1A1*2A variant allele (odds ratio (OR) 2.2 [1.0-4.9]) and with GSTM1 deletion (OR 2.3 [1.2-4.4]). Conversely, coffee drinking interacted negatively with NQO1 polymorphism in the case-only analysis (OR 0.6 [0.3-1.2] and 0.4 [0.1-1.0] for light and heavy coffee consumptions, respectively). This study suggests that maternal smoking may be a risk factor for leukaemia in children who carry CYP1A1 or GSTM1 genotypes, which might increase reactive metabolites of polycyclic aromatic hydrocarbons.

Background: Several toxicologic and epidemiologic studies have produced evidence that occupational exposure to polycyclic aromatic hydrocarbons (PAH) is a risk factor for ischemic heart disease (IHD). However, a clear exposure-response relation has not been demonstrated. Methods: We studied a relation between exposure to PAH and mortality from IHD (418 cases) in a cohort of 12,367 male asphalt workers from Denmark, Finland, France, Germany, Israel, The Netherlands and Norway. The earliest follow up (country-specific) started in 1953 and the latest ended in 2000, averaging 17 years. Exposures to benzo(a)pyrene were assessed quantitatively using measurement-driven exposure models. Exposure to coal tar was assessed in a semiquantitative manner on the basis of information supplied by company representatives. We carried out sensitivity analyses to assess potential confounding by tobacco smoking. Results: Both cumulative and average exposure indices for benzo(a)pyrene were positively associated with mortality from IHD. The highest relative risk for fatal IHD was observed for average benzo(a)pyrene exposures of 273 ng/m 3 or higher, for which the relative risk was 1.64 (95% confidence interval = 1.13-2.38). Similar results were obtained for coal tar exposure. Sensitivity analysis indicated that even in a realistic scenario of confounding by smoking, we would observe approximately 20% to 40% excess risk in IHD in the highest PAH-exposure categories. Conclusions: Our results lend support to the hypothesis that occupational PAH exposure causes fatal IHD and demonstrate a consistent exposure-response relation for this association. Copyright © 2005 by Lippincott Williams & Wilkins.

Cluster investigations remain an important public health issue as the number of reported clusters and public concern increase. This study shows how statistical considerations and a simulation tool may be helpful in providing communities with proper answers to the questions usually raised in such situations: How surprising is an observed childhood cancer excess? What could be learned from a statistical test? What could be learned from a case-control study? Using real demographic and incidence-rate data together with simulations based on the hypothesis that incidence rates are homogeneous, the probabilities of observing given situations were estimated. A number of real situations have been used as examples. The results of the simulation study showed, in detail, that no reliable information on the reality of an observed excess could be obtained a posteriori from a statistical test. A cluster of the same size may or may not be surprising, depending on the spatial area and time window to which the cases are related (i.e., the expected number of cases), and depending on the size of the referential territory to which this area is associated. The lack of power of a case-control study if no particular unusual exposure is present is also addressed. The approach described in this paper can easily be reproduced and adapted to many situations. It may be of assistance to health departments conducting cluster investigations and communicating with the public.

International audience; Epidemiological studies have been consistent in showing that cigarette smoking is inversely associated with Parkinson's disease (PD), whereas pesticide use is positively associated with PD. However, the relationship between PD and cigarette smoking remains poorly understood. Our objective was to study the relationship between cigarette smoking and PD in a population characterized by a high prevalence of pesticide exposure. This case-control study was carried out among subjects enrolled in the Mutualite Sociale Agricole, the French health insurance organization for workers connected to the agricultural world. We included 247 cases and 676 controls matched on age, sex, and region of residency. Information on smoking was obtained through in-person interviews. Pesticide exposure was assessed using a case-by-case expert evaluation procedure. We found an inverse relationship between ever cigarette smoking and PD (odds ratio [OR] = 0.6; 95% confidence interval [CI] = 0.4-0.9). The strength of this association increased with the number of pack-years. This relationship was present even when smoking was considered as long as 40 years before PD onset. An inverse association was also present among subjects professionally exposed to pesticides (OR = 0.5; 95% CI = 0.3-0.8) and was independent of the duration of exposure among men. We confirm the inverse association between cigarette smoking and PD in a population characterized by a high prevalence of professional pesticide exposure. The relationship between PD and cigarette smoking was not significantly modified or confounded by exposure to pesticides.

Alternative sources such as buccal cells have already been tested for genetic studies and epidemiological investigations. Thirty-seven volunteers participated in this study to compare cytology brushes, mouthwash, and treated cards for DNA collection. Quantity and quality of DNA and cost and feasibility were assessed. The mean DNA yield at 260 nm was found to be3.5,4, and2.6μg for cytobrushes, mouthwashes, and treated cards, respectively. A second quantification technique by fluorescence showed differences in the DNA yield with1.1and5.2μg for cytobrushes and mouthwash, respectively. All buccal samples allowed isolation of DNA suitable for polymerase chain reaction. According to the procedure of sample collection, the yield and purity of collected DNA, and storage conditions, the use of cytobrush appears to be the more appropriate method for DNA collection. This protocol has been validated and is currently applied in three large-scale multicentric studies including adults or children.

Analyses réalisées et leurs limitesLes observations réalisées sur les causes des 41 458 décès qui ont eu lieu du 1er au 20 août 2003 enFrance métropolitaine mettent en évidence les catégories de causes de décès les plus affectées parl'impact de la canicule, soit en terme de nombre de décès en excès, soit en terme d'accroissementrelatif du niveau de la mortalité habituelle et d'évolution de la structure des causes médicales dedécès.Nous avons présenté ici les observations réalisées sur des grands groupes de causes médicales dedécès et tenté de cerner les influences de l'âge, du sexe et du lieu de décès (hôpital-clinique,domicile, maison de retraite) sur l'accroissement de la mortalité observé.Nous n'avons par contre pas analysé, à cette étape, les modifications de la structure habituelle de lamortalité en fonction de l'intensité de la vague de chaleur qui a présenté de fortes disparitésgéographiques, reflétées par des disparités géographiques importantes de l'élévation de la mortalitégénérale.Les observations présentées sont basées à cette étape sur la seule cause rapportée comme initialesur le certificat de décès (une cause unique par décès) et ne prennent donc pas en compte l'ensembledes informations médicales figurant dans chaque certificat de décès. Ne sont donc pas présentées icide données caractérisant les associations entre causes de décès pour un même décès (analyse encauses multiples) ; par exemple, des données intégrant les pathologies déclarées simultanément auxmentions de déshydratation, hyperthermie ou coup de chaleur. Par ailleurs on peut penser que laconfiguration exceptionnelle de la mortalité durant la canicule a modifié non seulement la structurehabituelle des causes médicales de décès mais peut-être également les conditions de la notificationde ces décès par les médecins qui ont rempli les certificats de décès. Ces médecins ont eu à rendrecompte d'un processus morbide conduisant à la mort dans des conditions souvent inhabituelles etchez des sujets dont ils connaissaient probablement moins souvent les antécédents médicaux.L'analyse de la mortalité en causes multiples devrait permettre de cerner l'impact éventuel de tellesmodifications sur la structure de la mortalité.Principales observationsAu cours de la période du 1er au 20 août 2003, 41 458 décès ont été observés en Francemétropolitaine. L'analyse de leurs causes médicales, pour la population métropolitaine dans sonensemble, par classe d'âge, chez les hommes et chez les femmes, en fonction du lieu de décès(hôpital ou clinique, domicile, maison de retraite), met en évidence les points essentiels suivants :Causes médicales des décès en fonction de l'âge, chez les hommes et chez les femmes(1) Les excès de mortalité par cause statistiquement significatifs sont rares avant 45 ans, importantsentre 45 et 74 ans et très importants à partir de 75 ans. Chez les sujets âgés de moins de 45 ans, unesurmortalité, modérée, est observée uniquement chez les hommes. A partir de 45 ans, la surmortalitéest plus marquée chez les femmes.(2) Les causes médicales de décès qui ont le plus grand poids dans l'augmentation générale de lamortalité sont les causes directement liées à la chaleur (coup de chaleur, hyperthermie etdéshydratation : (+3 306), les maladies cardiovasculaires (+3 004), les symptômes et états morbidesmal définis (+ 1741), les maladies de l'appareil respiratoire (+1 365) et du système nerveux (+1 001).(3) Chez les sujets de moins de 45 ans, seules les causes de décès directement liées à la chaleur etles états morbides mal définis ont augmenté, et uniquement chez les hommes.(4) En fonction de l'accroissement relatif de la mortalité (O/E), on peut distinguer trois groupes decauses de décès chez les sujets de 45 ans et plus :- les causes directement liées à la chaleur (coup de chaleur, hyperthermie et déshydratation) dontl'augmentation relative a été massive (nombre de décès multiplié par 20 ou plus selon l'âge et le sexe),- les autres causes pour lesquelles la surmortalité a été extrêmement marquée : maladies du systèmenerveux, troubles mentaux, maladies de l'appareil respiratoire (incluant les pneumonies), maladiesinfectieuses, maladies de l'appareil génito-urinaire, maladies endocriniennes et états morbides maldéfinis,- la quasi-totalité des autres causes médicales a progressé mais d'une manière moins prononcée.(5) A partir de 45 ans, les progressions relatives des causes de décès sont toujours plus importanteschez les femmes que chez les hommes. Cette surmortalité féminine est statistiquement significative :- entre 45 et 74 ans pour les cancers du poumon et les morts violentes,- à partir de 75 ans pour les maladies infectieuses, génito-urinaires et cardiovasculaires.Causes médicales des décès en fonction des lieux de décès(1) En dehors des causes "directes" (coup de chaleur, hyperthermie et déshydratation), des maladiescardiovasculaires et des maladies respiratoires, pour lesquelles les excès de décès (O-E) sont lesplus marqués quel que soit le lieu de survenue du décès, les excès les plus importants sont observés :pour les cancers dans les hôpitaux et cliniques et pour les états morbides mal définis pour les décès àdomicile.(2) En dehors des causes médicales de décès qui ont présenté les progressions relatives (O/E) les plusimportantes quel que soit le lieu de décès (coup de chaleur, hyperthermie et déshydratation, maladies del'appareil respiratoire, du système nerveux, maladies infectieuses, maladies de l'appareil génito-urinaire,états morbides mal définis), certains contrastes dans la progression relative des décès apparaissent selonles lieux de décès :- augmentation moins importante dans les hôpitaux et plus importante dans les maisons de retraitepour les maladies cardiovasculaires,- progression moins élevée dans les établissements hospitaliers pour les troubles mentaux et étatsmorbides mal définis,Modifications majeures de la structure habituelle des causes médicales des décèsUn phénomène très spécifique à la canicule de 2003, non retrouvé dans les épisodes de caniculeprécédents en France (par exemple, effet de la canicule de 1976) est la fréquence des cas où lemédecin certificateur a déclaré en tant que cause initiale de décès, une cause directement liée à lasurvenue de la chaleur (déshydratation, hyperthermie, coup de chaleur). Le médecin certificateur avoulu ainsi indiquer que, même si la personne était âgée et porteuse de pathologies chroniqueslourdes au moment du décès, c'est la chaleur qui a été directement à l'origine de son décès, et qu'ellene serait pas décédée à cette date sans cet effet de la canicule. Cette très fréquente déclaration decauses directes est importante à appréhender, mais rend plus complexe l'analyse du poids des autrescauses de décès dans le niveau de la surmortalité générale.Outre ces causes directes, les autres pathologies ayant eu le poids le plus important dans l'excèsglobal de décès sont les maladies cardiovasculaires qui ont contribué pour 21% à l'accroissementgénéral de la mortalité, les états morbides mal définis (12%), les maladies de l'appareil respiratoire(9%) et les maladies du système nerveux (7%). La contribution du cancer a été seulement de 6%(alors que la mortalité par cancer représente habituellement 30% de la mortalité générale).

International audience; OBJECTIVES: To determine the number of women in France at least 50 years of age with risk factors for osteoporosis likely to lead to bone mineral density measurement, an investigation reimbursed by the French national health insurance system in patients at risk for osteoporosis. The study was commissioned by the French health authorities. MATERIALS AND METHODS: Risk factors for osteoporosis were defined as recommended by the French Agency for Accreditation and Evaluation in Health (ANAES) in 2001. The study data were from nine cohort studies done in France and from the National Health Insurance Agency for the Rhone-Alpes region of France. Risk factor prevalences in France were standardized by extrapolation according to the age distribution in France. RESULTS: Overall, data were collected in 123,986 women aged 50 years or older. From these data, risk factor estimates were as follows: menopause before 40 years of age, 1.5 million women; body mass index (BMI) lower than 19 kg/m(2), nearly 700,000; history of fracture, more than 2 million; history of femoral neck fracture in the mother, more than 1 million; history of health problems potentially responsible for osteoporosis, 400,000; and history of long-term glucocorticoid therapy, 612,000. In all, 3,186,318 (30%) women were estimated to have at least one risk factor and 785,512 (7.5%) at least two risk factors. CONCLUSIONS: Although our study sample was not representative of the population residing in France, the large sample size and diversity of data sources support the validity of our estimate of the prevalence of risk factors for osteoporosis in postmenopausal women living in France.

International audience; BACKGROUND: The Saitohin gene has recently been identified in intron 9 of the Tau gene. Because an association between Parkinson's disease and Tau has been described, Saitohin represents a candidate gene for Parkinson's disease. OBJECTIVE: To test these two genes for their association with Parkinson's disease in a large community based case-control study. RESULTS: Cases (n = 208) were more often homozygotes for the Tau H1 haplotype than controls (n = 483; odds ratio (OR) = 1.71 (95% confidence interval, 1.20 to 2.43); p = 0.003), and the saitohin Q allele was in complete linkage disequilibrium with the H1 haplotype. This association was stronger among cases with Parkinson's disease onset below 65 years (< or =65 years: OR = 2.52 (1.49 to 4.25); p65 years: OR = 1.20 (0.73 to 1.98); p

International audience; We performed a case-control study of Parkinson's disease (PD) in a population characterized by a high prevalence of pesticide exposure and studied the joint effect of pesticide exposure and CYP2D6. Although they are based on a small group of subjects with the joint exposure, our findings are consistent with a gene-environment interaction disease model according to which (1) pesticides have a modest effect in subjects who are not CYP2D6 poor metabolizers, (2) pesticides' effect is increased in poor metabolizers (approximately twofold), and (3) poor metabolizers are not at increased PD risk in the absence of pesticide exposure.

International audience; Neuroblastoma is the most common cancer in infants worldwide, but little is known about its etiology. Infectious etiologies involving the immune system have been hypothesized for some childhood cancers, especially leukemia, but the role of infectious agents in neuroblastoma has not been fully investigated. The authors used data from a large case-control study conducted by the Children's Oncology Group in the United States and Canada in 1992-1994 to investigate whether there was any relation among day-care attendance, childhood infections, allergies, and neuroblastoma. They interviewed mothers of 538 case children and 504 age-matched control children by telephone about several factors, including pregnancy, medical history, lifestyle, and childhood medical conditions and exposures. The results suggested decreased risks associated with day-care attendance (odds ratio (OR) = 0.81, 95% confidence interval (CI): 0.56, 1.17), childhood infectious diseases (chickenpox, mumps, red measles, and German measles) (OR = 0.60, 95% CI: 0.39, 0.93), and allergies (OR = 0.68, 95% CI: 0.44, 1.07). The authors found reduced neuroblastoma risk associated with markers of potential childhood infections. This suggests a possible role of infectious agents in neuroblastoma etiology. Future epidemiologic studies should incorporate more direct data on infection.

Overall, 670 cases (O) of childhood leukaemia were diagnosed within 20 km of the 29 French nuclear installations between 1990 and 1998 compared to an expected number (E) of 729.09 cases (O/E=0.92, 95% confidence interval (CI)=[0.85-0.99]). Each of the four areas defined around the sites showed non significant deficits of cases (0-5 km: O=65, O/E=0.87, CI=[0.67-1.10]; 5-10 km: O=165, O/E=0.95, CI=[0.81-1.10]; 10-15 km: O=220, O/E=0.88, CI=[0.77-1.00]; 15-20 km: O=220, O/E=0.96, CI=[0.84-1.10]). There was no evidence of a trend in standardised incidence ratio with distance from the sites for all children or for any of the three age groups studied. Similar results were obtained when the start-up year of the electricity-generating nuclear sites and their electric nuclear power were taken into account. No evidence was found of a generally increased risk of childhood leukaemia around the 29 French nuclear sites under study during 1990-1998.

International audience; 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.

Aim: To analyse the association between potential environmental exposure to hydrocarbons and the risk of acute childhood leukaemia. Methods: A hospital based multicentre case control study, stratified on centre, age, and sex, with 280 leukaemia cases and 285 controls was carried out. Data were collected by a standardised interview of the mothers. Results: No clear association was seen between maternal occupational exposure to hydrocarbons during pregnancy and leukaemia, or between residential traffic density and leukaemia. There was an association between dwellings neighbouring a petrol station or a repair garage during childhood and the risk of childhood leukaemia (OR 4.0, 95% CI 1.5 to 10.3), with a duration trend. The association, which appeared particularly strong for acute non-lymphocytic leukaemia (OR 7.7, 95% CI 1.7 to 34.3), was not altered by adjustment for potential confounding factors. Conclusions: Results showed an association between acute childhood leukaemia and dwellings neighbouring auto repair garages and petrol stations, which are benzene emitting sources. These findings could be due to chance, although the strength of the association and the duration trend are arguments for a causal association.

Item does not contain fulltext The hypothesis that asphalt workers are at increased risk of mortality from industrial accidents and other external causes was tested. Mortality rates for external and violent causes of death in a cohort of asphalt industry employees from seven European countries and Israel were compared to that of the general population. There was no evidence that mortality from external causes was increased among long term employees in asphalt application and mixing. There was an increased risk for mortality due to external causes among short term workers. However, none of the fatal accidents among short term workers appear to have occurred during employment in the studied asphalt companies. Overall, no evidence was found supporting the hypothesis that asphalt workers are at increased risk of fatal industrial or road accidents. Mortality from other external causes did not increase in this population as a whole, but increased risks among short term workers deserve further attention.

La France métropolitaine a connu dans la première quinzaine d'août 2003 une vague de chaleur d'une intensité et d'une durée sans précédent dapuis le début des enregistrements météorologiques au 19ème siècle. Cette vague de chaleur s'est accompagnée d'une vague de surmortalité à court terme d'une importance également exceptionnelle : pour la seule journée du 4 août, près de 300 décès ont été observés en excès par rapport aux années précédentes ; l'excès a augmenté régulièrement et massivement jusqu'à atteindre, pour la journée du 12 août, plus de 2000 décès. A partir du 19 août et au cours de la semaine qui a suivi la mortalité quotidienne a retrouvé un niveau normal. Au total, le nombre cumulé des décès en escès par rapport aux années précédentes a été d'environ 400 le 4 août, 3900 le 8 août, 10600 le 12 août et 14800 le 20 août, soit une augmentation de 60% par rapport à la mortalité attendue. Sur la base des informations disponibles à cette étape, il est encore difficile de savoir s'il y a eu une augmentation de la mortalité des sujets de moins de 45 ans, l'estimation étant plus incertaine sur ces effectifs faibles. La surmortalité observée à partir de 45 ans est importante, croissante avec l'âge : +20% chez les sujets âgés de 45 à 54 ans, +40% chez les sujets âgés de 55 à 74 ans, +70% chez les sujets âgés de 75 à 94 ans et + 120% chez les sujets de 95 ans et plus. L'importante surmortalité observée entre le 1er au 20 août 2003 a concerné aussi bien les femmes que les hommes. Toutefois, la surmortalité observée chez les femmes (+70%) est sensebliement plus élevée que celle qui a été observée chez les hommes (+40%). La surmortalité a été particulièrement importante dans les régions Centre (+103%) et Ile-de-France (+134%), notamment dans l'agglomération parisienne : +127% à Paris, +147% dans l'Essonne, +161% dans les Hauts-de-Seine, +160% en Seine Saint-Denis et +171% dans le Val de Marne. L'analyse de la relation spatio-temporelle entre la surmortalité et le degré d'élévation de la température a permis de mettre en évidence une surmortalité du 1er au 20 août significative même dans les départements où le nombre de jours de canicule était faible. Cette surmortalité était plus élevée dans les populations des départements exposées à 2 à 5 jours de grande chaleur de ce type (+52%) et plus élevée encore dans les populations des départements exposées à 6 jours ou plus de grande chaleur(+83%). Les départements ont subi une surmortalité d'autant plus importante que le nombre de jours consécutifs avec des maximales supérieures à 35°C a été élevé. Ainsi, chez les sujets de 75 ans et plus, plus de 1200 décès ont été observés après 9 jours d'affilée dépassant 35°C. La srmortalité a ensuite décru progressivement après le retour des maximales au-dessous de 30°C. Nous avons également montré que les différents facteurs associés à la surmortalité - âge, sexe, degré d'urbanisation, durée de la canicule - agissaient de façon synergique. Les nombres de décès qui ont eu lieu à domicile et en maison de retraite ont été multipliés environ par 2 par rapport à leur valeur habituelle. Au total, 42% des décès en excès sont survenus dans des hôpitaux, 35% à domicile, 19% dans des maisons de retraite et 3% en clinique privée. L'interprétation de ces résultats doit être faite avec prudence dans la mesure où l'état de santé des sujets résidant ou transférés dans les différentes structures de soins varie et que ce facteur est déterminant pour expliquer le niveau de mortalité. Les augmentations de mortalité les plus importantes sont observées pour des causes de décès directement attribuables à la chaleur : déshydratation, hyperthermie, canicule. Viennent ensuite les maladies de l'appareil génito-urinaire et des maladies de l'appareil respiratoire. La plupart des autres causes de décès sont concernées par la surmortalité mais avec des progressions nettement moins marquées pour les tumeurs, pour les suicides et pour les accidents de la circulation. La canicule a fortement modifié la répartition habituelle de la mortalité par causes. Dans les décès en excès de 2003, les causes liées directement à la canicule représentent 28,9% du total des décès, proportion négligeable les années précédentes, alors que les tumeurs représentent 5,5% des décès, contre 30,4% dans la structure habituelle de la mortalité.

International audience; OBJECTIVE: The aryl hydrocarbon receptor repressor (AhRR) protein may dimerize with the AhR nuclear translocator (ARNT) and may compete with the aryl hydrocarbon receptor (AhR) to bind the xenobiotic responsive elements. The result is a negative feedback mechanism that involves a down regulation of all genes regulated by the AhR transcription factor which positively regulates the expression of the Cytochrome P-4501A1 gene (CYP1A1). METHODS: The structure of the AhRR gene was reconstituted, then the genetic polymorphisms of this gene including the promoter were investigated and the link between these polymorphisms, CYP1A1 inducibility and lung cancer incidence in a French population was examined. Four polymorphisms were found, two in the coding region (609G>C and 1977G>C) and two in the 5'-untranslated region (-96G>A and -869A>T). Among the four polymorphisms, only one, the 609G>C has been previously described. The 609G>C and 1977G>C are localized respectively in exon 6 and 12 and lead to Pro554Ala and Asp641His substitutions, respectively. To evaluate the frequency of these allelic variants, a DNA library of a case-control study of lung cancer (164 controls and 171 patients) was screened. These polymorphisms were detected at the same allele frequency (0.40 for 609C, 0.05 for 1977C, 0.24 for -96A and 0.17 for -869T) in both controls and patients. Statistical analysis did not show any relationship between all the mutations found and CYP1A1 inducibility and lung cancer incidence. CONCLUSION: None of the polymorphisms were found to play a key role in CYP1A1 inducibility or in the susceptibility to develop lung cancer.

Background A genetic component of early-onset lung cancer has been suggested. The role of metabolic gene polymorphisms has never been studied in young lung cancer cases. Phase 1 and Phase 2 gene polymorphisms are involved in tobacco carcinogens' metabolism and therefore in lung cancer risk. Methods The effect of metabolic gene polymorphisms on lung cancer at young ages was studied by pooling data from the Genetic Susceptibility to Environmental Carcinogens (GSEC) database. All primary lung cancer cases of both sexes who were Caucasian and less than or equal to45 years of age at diagnosis, and the corresponding controls were selected. We obtained 261 cases and 1452 controls. Results There was a marginally significant association between lung cancer and GST1 null genotype (OR = 1.2; 95% Cl: 1.0-1.6), and a significant association between lung cancer and the homozygous CYP1A1 Msp1 variant allele (CYP1A1*2A and *2B) genotype (OR = 4.7 95% Cl: 1.2-19.0). When data were stratified by smoking status, the association between CYP1A1 genotype and lung cancer was confined to never smokers. Conclusions These results suggest that metabolic genetic factors play a role in lung cancer developing at young ages. (Less)

International audience; We studied the relationship between Parkinson's disease (PD) and the S18Y polymorphism in the UCH-L1 gene and the effect on this relationship of age at onset, smoking, and pesticides. Patients requested free health coverage for PD to the Mutualit?ociale Agricole (MSA), the French health insurance organization for people whose work is related to agriculture. Controls requested reimbursement of health expenses to the MSA. A maximum of three controls were matched to each case. Analyses included participants with both parents born in Europe. There were no differences in S18Y genotypes between patients (n = 209; 67% SS, 32% SY, 1% YY) and controls (n = 488; 66% SS, 30% SY, 4% YY). The relationship between PD and S18Y was modified by age at onset (P = 0.03). The Y allele was inversely associated with PD for patients with onset before 61 years (odds ratio [OR] = 0.53; 95% confidence interval [CI], 0.29-0.99); there was no association for older patients (62-68 years: OR = 1.21; 95% CI, 0.67-2.20; >68 years: OR = 1.24; 95% CI, 0.67-2.31). Among patients, Y carriers had a later onset than noncarriers (P = 0.04). These findings were not modified or confounded by smoking and pesticides. In this community-based case-control study, carriers of the Y allele were at decreased risk of developing PD at a young age, independently of pesticides and smoking.

Background We compared performance of different exposure assessment approaches in a cohort study of cancer risk among European asphalt workers. Methods Three bitumen fume exposure indices (duration of exposure (years), average exposure (mg/m3) and cumulative exposure (mg/m3*years)) and two latency models (with and without a 15 year lag) were considered for an association between lung cancer mortality and bitumen fume. Results There was no association between lung cancer risk and either duration or cumulative exposure. However, there was the suggestion of an increase in lung cancer risk accompanying rise in average exposure. Only models with average bitumen fume exposure (with or without lag) improved model fit, albeit to the same extent. Conclusions Constructing quantitative indices of exposure intensity was justified because they produced the greatest improvement in fit of models that explored possible relationship between bitumen fume exposure and lung cancer risk. The identified associations require further investigation. Am. J. Ind. Med. 43:40–48, 2003. © 2003 Wiley‐Liss, Inc.

BACKGROUND: In conjunction with the European cohort study among asphalt workers coordinated by the International Agency for Research on Cancer (IARC), we studied the mortality of 15,011 French men who were followed for 17 years for a total of 175,062 persons-years. This group contained 2,506 subjects who had ever been employed as asphalt workers: they contributed 30,692 person-years of risk. A reference group was composed of 6,675 subjects (i.e., 61,856 persons-years) who had been employed only in building or ground construction. METHODS: Mortality ratios standardized for age and period were computed with their 95% confidence intervals (CI) from the age and period mortality rates of all French men for the years covered by the study (1979-1996). We also compared the mortality of exposed workers and the reference group with Poisson regression models after adjustment for age, calendar period, and either duration of employment or length of follow-up. RESULTS: Mortality from lung cancer was equivalent to the expected rate [SMR = 1.01 95% CI (0.6-1.6)], but was 40% greater than among the non-exposed reference group [RR = 1.4 95% CI (0.7-2.8)]. We also found an excess of gastrointestinal cancers, especially of the esophagus [SMR = 1.94, 95% CI (0.9-3.6)] and stomach [SMR = 2.2, 95% CI (0.8-4.7)]. Comparison with the internal reference group confirmed these findings, especially for stomach cancer [RR = 2.8, 95% CI (0.7-11.4)]. CONCLUSIONS: Although our results are not statistically significant, they suggest that road-paving workers may have a slightly higher rate of lung cancer and a moderately higher rate of stomach cancer than their non-exposed counterparts. The excess of lung cancer may be due to potential confounding factors, including the occupational risk factor of coal tar exposure and the lifestyle risk factor of smoking. A nested case-control study is under way that will make it possible to control for smoking and other potential carcinogenic exposures; this is necessary before any definitive conclusions can be drawn.

International audience; Excess of nitric oxide (NO) has been shown to exert neurotoxic impacts in the brain. Moreover, inhibition of two NO-synthesizing enzymes, neuronal NOS (nNOS) and inducible NOS (iNOS), displays neuroprotective effects in the MPTP model of Parkinson's disease (PD). These data suggest a possible involvement of NOS as factors controlling the resistance of the nigral dopaminergic neurons to environmental insults. Therefore, we investigated whether polymorphisms present in these genes could contribute to the risk of developing PD. We carried out a community-based case-control study among subjects enrolled in the Mutualit?ociale Agricole, the French health insurance organization for workers connected to agriculture. Two-hundred and nine PD patients and 488 controls of European (mostly French) ancestry and matched for age, sex and region of residency were included in this study. Associations were observed with polymorphisms present in exon 22 of iNOS (OR for AA carriers=0.50, 95% CI=0.29-0.86, P=0.01) and in exon 29 of nNOS (OR for carriers of the T allele=1.53, 95% CI=1.08-2.16, P=0.02); no association was observed with a polymorphism in exon 18 of nNOS (OR for carriers of the T allele=1.20, 95% CI=0.85-1.69, P=0.30). Moreover, a significant interaction of the nNOS polymorphisms with current and ever cigarette smoking was found (nNOS 18, P=0.05; nNOS 29, P=0.04). All together, these data favour an involvement of these two genes as new modifier genes in PD.

International audience; Myeloperoxidase (MPO) is an haemoprotein that metabolizes tobacco smoke procarcinogens such as benzo(a)pyrene and aromatic amines into highly reactive intermediates. A polymorphism in the MPO promoter (-463G>A), resulting in lower expression, was previously associated with a decrease in lung cancer risk. In this study, the MPO gene was analysed for new polymorphisms by denaturing high-performance liquid chromatography and sequencing on a panel of 48 subjects. Subsequently, the association between newly described polymorphisms, the -463G>A single nucleotide polymorphism (SNP) and lung cancer risk was investigated in a case-control study comprising 245 Caucasian cases and 249 Caucasian controls. Genetic polymorphisms were found in exons 2 (V53F), 6 (M251T), 7 (A332V), 11 (I642L) and 12 (I717V), with allelic frequencies of 6.0%, 1.8%, 1.8%, 0.2% and 1.8%, respectively. A new polymorphism located in the intron 11 3' splice site was found (0.4%). The known -463G>A polymorphism (24.0%) and four new polymorphisms in promoter region were also detected. No correlation between these new polymorphisms and lung cancer risk was found. For the -463G>A polymorphism, no modification of lung cancer risk was observed for either the G/A genotype [odds ratio (OR) 1.19; 95% confidence interval (CI) 0.8-1.8] or the A/A genotype (OR 0.97; 95% CI 0.4-2.6). Linkage analysis showed a strong disequilibrium between -463G>A polymorphism and exonic SNPs. However, the distribution of reconstructed haplotypes did not differ significantly between cases and controls. Further studies need to be performed to investigate the role of these polymorphisms in others diseases.

Background Inhalation of bitumen fumes is potentially carcinogenic to humans. Methods We conducted a study of 29,820 male workers exposed to bitumen in road paving, asphalt mixing and roofing, 32,245 ground and building construction workers unexposed to bitumen, and 17,757 workers not classifiable as bitumen workers, from Denmark, Finland, France, Germany, Israel, the Netherlands, Norway, and Sweden, with mortality follow‐up during 1953–2000. We calculated standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) based on national mortality rates. Poisson regression analyses compared mortality of bitumen workers to that of building or ground construction workers. Results The overall mortality was below expectation in the total cohort (SMR 0.92, 95% CI 0.90–0.94) and in each group of workers. The SMR of lung cancer was higher among bitumen workers (1.17, 95% CI 1.04–1.30) than among workers in ground and building construction (SMR 1.01, 95% CI 0.89–1.15). In the internal comparison, the relative risk (RR) of lung cancer mortality among bitumen workers was 1.09 (95% CI 0.89–1.34). The results of cancer of the head and neck were similar to those of lung cancer, based on a smaller number of deaths. There was no suggestion of an association between employment in bitumen jobs and other cancers. Conclusions European workers employed in road paving, asphalt mixing and other jobs entailing exposure to bitumen fume might have experienced a small increase in lung cancer mortality risk, compared to workers in ground and building construction. However, exposure assessment was limited and confounding from exposure to carcinogens in other industries, tobacco smoking, and other lifestyle factors cannot be ruled out. Am. J. Ind. Med. 43:18–27, 2003. © 2003 Wiley‐Liss, Inc.

Background An increased risk of lung cancers among asphalt workers has been suggested in epidemiological studies based on large scale statistical analyses. Methods In a multi‐country study of 29,820 male workers employed in road paving, asphalt mixing and roofing, 32,245 ground and building construction workers and 17,757 other workers from Denmark, Finland, France, Germany, Israel, the Netherlands, Norway, and Sweden, with mortality that was documented from 1953–2000. Exposures to bitumen fume, coal tar, 4–6 ring polycyclic aromatic hydrocarbons, organic vapor, diesel exhaust, asbestos, and silica dust were assessed via a job‐exposure matrix. Standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) based on national mortality rates, as well as relative risks (RRs) based on Poisson regression models were calculated. Results The SMR of lung cancer among workers exposed to bitumen fume (1.08, 95% CI 0.99–1.18) was comparable to that of non‐exposed workers (SMR 1.05, 95% CI 0.92–1.19). In a sub‐cohort of bitumen‐exposed workers without exposure to coal tar, the SMR of lung cancer was 1.23 (95% CI 1.02–1.48). The analysis based on the semi‐quantitative, matrix‐based exposures in the whole cohort did not suggest an increased lung cancer risk following exposure to bitumen fume. However, in an analysis restricted to road pavers, based on quantitative estimate of bitumen fume exposure, a dose‐response was suggested for average level of exposure, applying a 15‐year lag, which was marginally reduced after adjustment for co‐exposure to coal tar. The results for cancer of the head and neck were similar to those of lung cancer, although they were based on a smaller number of deaths. There was no clear suggestion of an association with bitumen fume for any other neoplasm. Conclusions The results of the analysis by bitumen fume exposure do not allow us to conclude on the presence or absence of a causal link between exposure to bitumen fume and risk of cancer of the lung and the head and neck. Am. J. Ind. Med. 43:28–39, 2003. © 2003 Wiley‐Liss, Inc.

Item does not contain fulltext Work in the asphalt industry has been associated with nonmalignant respiratory morbidity and mortality, but the evidence is not consistent. A historical cohort of asphalt workers included 58,862 men (911,209 person-years) first employed between 1913 and 1999 in companies applying and mixing asphalt in Denmark, Finland, France, Germany, Israel, the Netherlands, and Norway. The relations between mortality from nonmalignant respiratory diseases (including the obstructive lung diseases: chronic bronchitis, emphysema, and asthma) and specific chemical agents and mixtures were evaluated using a study-specific exposure matrix. Mortality from obstructive lung diseases was associated with the estimated cumulative and average exposures to polycyclic aromatic hydrocarbons and coal tar (p values of the test for linear trend = 0.06 and 0.01, respectively). The positive association between bitumen fume exposure and mortality from obstructive lung diseases was weak and not statistically significant; confounding by simultaneous exposure to coal tar could not be excluded. The authors lacked data on smoking and full occupational histories. In conclusion, exposures to polycyclic aromatic hydrocarbons, originating from coal tar and possibly from bitumen fume, may have contributed to mortality from obstructive lung diseases among asphalt workers, but confounding and bias cannot be ruled out as an explanation for the observed associations.

Background An exposure matrix (EM) for known and suspected carcinogens was required for a multicenter international cohort study of cancer risk and bitumen among asphalt workers. Methods Production characteristics in companies enrolled in the study were ascertained through use of a company questionnaire (CQ). Exposures to coal tar, bitumen fume, organic vapor, polycyclic aromatic hydrocarbons, diesel fume, silica, and asbestos were assessed semi‐quantitatively using information from CQs, expert judgment, and statistical models. Exposures of road paving workers to bitumen fume, organic vapor, and benzo(a)pyrene were estimated quantitatively by applying regression models, based on monitoring data, to exposure scenarios identified by the CQs. Results Exposures estimates were derived for 217 companies enrolled in the cohort, plus the Swedish asphalt paving industry in general. Most companies were engaged in road paving and asphalt mixing, but some also participated in general construction and roofing. Coal tar use was most common in Denmark and The Netherlands, but the practice is now obsolete. Quantitative estimates of exposure to bitumen fume, organic vapor, and benzo(a)pyrene for pavers, and semi‐quantitative estimates of exposure to these agents among all subjects were strongly correlated. Semi‐quantitative estimates of exposure to bitumen fume and coal tar exposures were only moderately correlated. EM assessed non‐monotonic historical decrease in exposures to all agents assessed except silica and diesel exhaust. Conclusions We produced a data‐driven EM using methodology that can be adapted for other multicenter studies. Am. J. Ind. Med. 43:3–17, 2003. © 2003 Wiley‐Liss, Inc.

Some of the glutathione S-transferases (GSTs) are polymorphic and may play a role in lung cancer susceptibility. Our previous study in a French Caucasian study population suggested GSTM1 null genotype as a moderate risk factor for lung cancer. Here we extended the study to investigate the potential role of GSTT1 and GSTP1 polymorphisms in susceptibility to lung cancer, either separately or in combination. The study population consisted of 268 controls and 251 cases. Nineteen percent of the controls and 15% of the cases had GSTT1 null genotype. The distribution of GSTP1*A/*A, *A/*B and *B/*B genotypes were 46.9, 45.5 and 7.6% in controls, and 47.8, 40.2 and 12.0% in cases, respectively. No statistically significant effects in the lung cancer risk were observed for the GSTT1 genotypes, but the GSTP1*B/*B genotype posed a 2-fold risk [odds ratio (OR) = 2.0, 95% confidence interval (CI) 1.0-4.1] of this malignancy compared with the GSTP1*A allele containing genotypes; this association was mainly attributable to small cell lung cancer (OR = 3.6, 95% CI 1.3-9.8). The most remarkable risk was seen for the small cell carcinoma among subjects with the GSTP1*B/*B genotype and concurrent lack of the GSTM1 gene (OR = 6.9, 95% CI 1.6-30.2). The deficient genotypes for GSTM1 and GSTP1 seem thus to be important risk modifiers for lung cancer, especially in combination.

We conducted a case–control study to investigate the role of early infections in the aetiology of childhood acute leukaemias. The study included 280 incident cases (240 acute lymphoblastic leukaemia and 40 acute non-lymphoblastic leukaemia) and 288 hospital controls, frequency matched by age, gender, hospital, catchment area of the hospital and ethnic origin. Data were obtained from standardised face-to-face interviews of the mothers. The interviews included questions on early common infections, day-care attendance, breast-feeding, birth order and infantile diseases. Odds ratios were estimated using an unconditional regression model including the stratification variables, parental socio-economic status and perinatal characteristics. Birth order was not associated with childhood leukaemia (acute lymphoblastic or acute non-lymphoblastic). A statistically-significant inverse association was observed between childhood leukaemia and day-care attendance (odds ratio=0.6, 95% Confidence Interval=(0.4–1.0)), repeated early common infections (⩾4 per year before age two, odds ratio=0.6 (0.4–1.0)), surgical procedures for ear–nose–throat infections before age two (odds ratio=0.5 (0.2–1.0)) and prolonged breast-feeding (⩾6 months, odds ratio=0.5 (0.2–1.0)). In the multivariate model including day-care attendance, early common infections and breast-feeding, results concerning breast-feeding remained unchanged. A statistically significant interaction between day-care attendance and repeated early common infections was observed. When the interaction was taken into account, the simple effects of day-care and early common infections disappeared (odds ratio=1.1 (0.5–2.3) and odds ratio=0.8 (0.5–1.3), respectively) while the joint effect of day-care attendance and early common infections was negatively associated with childhood leukaemia (odds ratio=0.3 (0.1–0.8)). All the above associations were observed both for acute lymphoblastic leukaemia and acute non-lymphoblastic leukaemia. Our results support Greaves' hypothesis, even though they are not specific of common leukaemia. British Journal of Cancer (2002) 86, 1064–1069. DOI: 10.1038/sj/bjc/6600091 www.bjcancer.com © 2002 Cancer Research UK

La lombalgie se définit par la présence de douleurs. Plus précisément, la lombalgie désigne toute manifestation douloureuse siégeant dans la partie basse de la colonne vertébrale, c’est-à-dire entre la charnière dorso-lombaire(D12-L1) et la charnière lombo-sacrée (L5-S1). En ce sens, la lombalgie commune n’est pas une entité pathologique : c’est un symptôme pouvant répondre à la souffrance mécanique de structures rachidiennes et péri rachidiennes diverses.(...)Dans l’affirmation « mal de dos, mal du siècle », il y a à la fois du vrai, du faux et de l’imprécis :• du vrai, en ce sens que la lombalgie est une affection très fréquente en population adulte puisque dans différentes enquêtes, environ 60 % des adultes,parfois plus, déclarent souffrir ou avoir souffert de lombalgie ;• du faux, en ce sens que la lombalgie est une affection bénigne dont l’évolution spontanée est favorable dans la majorité des cas. En effet, les enquêtes disponibles montrent que seulement une lombalgie sur cinq, en moyenne,entraîne un arrêt de travail. Parmi ces arrêts, la majorité sont des arrêts courts(55 % entre 1 et 7 jours dans l’enquête EDF-GDF) ;• de l’imprécis dans la mesure où dire : « 60 à 80 % des adultes souffrent ou ont souffert de lombalgie » signifie que 60 à 80 % des adultes répondraient ouià une question portant sur des douleurs, intenses ou légères, passagères oudurables, dans un passé lointain ou proche ou pour le présent. Avec unedéfinition beaucoup plus stricte, par exemple l’existence d’un arrêt de travailpour lombalgie dans les 12 derniers mois, on obtient une fréquence beaucoupplus faible (de l’ordre de 5 à 10 %).

International audience; The association between a familial history of autoimmune disease and childhood acute leukemia was investigated in a French case-control study that, overall, was designed to assess the role of perinatal, infectious, environmental, and genetic factors in the etiology of childhood acute leukemia. Familial histories of autoimmune disease in first- and second-degree relatives were compared in 279 incident cases, 240 cases of acute lymphocytic leukemia (ALL) and 39 cases of acute non-lymphoblastic leukemia (ANLL), and 285 controls. Recruitment was frequency matched by age, gender, hospital, and ethnic origin. Odds ratios (OR) were estimated using an unconditional regression model taking into account the stratification variables, socioeconomic status, and familial structure. A statistically significant association between a history of autoimmune disease in first- or second-degree relatives and ALL (OR, 1.7; 95% confidence interval (CI), 1.0-2.8) was found. A relationship between thyroid diseases overall and ALL (OR, 2.0; 95% CI, 1.0-3.9) was observed. This association was more pronounced for potentially autoimmune thyroid diseases (Grave's disease and/or hyperthyroidism and Hashimoto's disease and/or hypothyroidism) (OR, 3.5; 95% CI, 1.1-10.7 and OR, 5.6; 95% CI, 1.0-31.1, respectively for ALL and ANLL), whereas it was not statistically significant for the other thyroid diseases (thyroid goiter, thyroid nodule, and unspecified thyroid disorders) (OR, 1.6; 95% CI, 0.7-3.5 and OR, 1.3; 95% CI, 0.2-7.0, respectively, for ALL and ANLL). The results suggest that a familial history of autoimmune thyroid disease may be associated with childhood acute leukemia.