Éditeur(s) : HAL CCSD
Résumé : International audience
Women who drink light-to-moderately during pregnancy have been observed to have lower risk of unfavourable pregnancy outcomes than abstainers. This has been suggested to be a result of bias. In a pooled sample, including 193 747 live-born singletons from nine European cohorts, we examined the associations between light-to-moderate drinking and preterm birth, birth weight, and small-for-gestational age in term born children (term SGA). To address potential sources of bias, we compared the associations from the total sample with a sub-sample restricted to first-time pregnant women who conceived within six months of trying, and examined whether the associations varied across calendar time. In the total sample, drinking up to around six drinks per week as compared to abstaining was associated with lower risk of preterm birth, whereas no significant associations were found for birth weight or term SGA. Drinking six or more drinks per week was associated with lower birth weight and higher risk of term SGA, but no increased risk of preterm birth. The analyses restricted to women without reproductive experience revealed similar results. Before 2000 approximately half of pregnant women drank alcohol. This decreased to 39% in 2000–2004, and 14% in 2005–2011. Before 2000, every additional drink was associated with reduced mean birth weight, whereas in 2005–2011, the mean birth weight increased with increasing intake. The period-specific associations between low-to-moderate drinking and birth weight, which also were observed for term SGA, are indicative of bias. It is impossible to distinguish if the bias is attributable to unmeasured confounding, which change over time or cohort heterogeneity. © 2017, Springer Science+Business Media B.V.
ISSN: 03932990

hal-01647159
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01647159
DOI : 10.1007/s10654-017-0323-2
PUBMED : 29027084

Éditeur(s) : HAL CCSD National Institute of Environmental Health Sciences (NIEHS) National Institute of Environmental Health Sciences
Résumé : International audience
Long-term exposure to persistent pollutants with hormonal properties (endocrine-disrupting chemicals, EDCs) may contribute to the risk of prostate cancer (PCa). However, epidemiological evidence remains limited. We investigated the relationship between PCa and plasma concentrations of universally widespread pollutants, in particular p,p'-dichlorodiphenyl dichloroethene (DDE) and the non-dioxin like polychlorinated biphenyl congener 153 (PCB153). We evaluated before treatment 576 men with newly diagnosed PCa and 655 controls in Guadeloupe (French West Indies). Exposure was analyzed according to case-control status. Associations were assessed by unconditional logistic regression analysis, controlling for confounding factors. Missing data were handled by multiple imputation. We estimated a significant positive association between DDE and PCa (adjusted odds ratio [OR] 1.53; 95% CI 1.02, 2.30 for the highest versus lowest quintile of exposure; PTrend = 0.01). PCB153 was inversely associated with PCa (OR 0.30; 95% CI 0.19, 0.47 for the highest versus lowest quintile of exposure values; PTrend < 0.001). Also, PCB153 was more strongly associated to low-grade than high grade PCa. Associations of PCa with DDE and PCB153 were in opposite directions. This may reflect differences in the mechanisms of action of these EDCs, and although our findings need to be replicated in other populations, they are consistent with complex effects of EDCs on human health.
ISSN: 0091-6765

hal-01118553
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118553
DOI : 10.1289/ehp.1408407
PUBMED : 25493337

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Aims: The aims of this study were to compare short-and long-term outcomes for clinical T2N0 oesophageal cancer with analysis of (i) primary surgery (S) versus neoadjuvant therapy plus surgery (NS), (ii) squamous cell carcinoma and adenocarcinoma subsets; and (iii) neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy.Methods: Data were collected from 30 European centres from 2000 to 2010. Among 2944 included patients, 355 patients (12.1%) had cT2N0 disease; 285 (S) and 70 (NS), were compared in terms of short-and long-term outcomes. Propensity score matching analyses were used to compensate for differences in baseline characteristics.Results: No significant differences between the groups were shown in terms of in hospital morbidity and mortality. Nodal disease was observed in 50% of S-group at the time of surgery, with 20% pN2/N3. Utilisation of neoadjuvant therapy was associated with significant tumour downstaging as reflected by increases in pT0, pN0 and pTNM stage 0 disease, this effect was further enhanced with neoadjuvant chemoradiotherapy. After adjustment on propensity score and confounding factors, for all patients and subset analysis of squamous cell and adenocarcinoma, neoadjuvant therapy had no significant effect upon survival or recurrence (overall, loco-regional, distant or mixed) compared to surgery alone. There were no significant differences between neoadjuvant chemotherapy and chemoradiotherapy in short-or long-term outcomes.Conclusion: The results of this study suggest that a surgery alone treatment approach should be recommended as the primary treatment approach for cT2N0 oesophageal cancer despite 50% of patients having nodal disease at the time of surgery.
ISSN: 0959-8049

hal-01666517
https://hal.univ-lorraine.fr/hal-01666517
DOI : 10.1016/j.ejca.2015.11.024

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Few studies have explored the consequences of environmental exposure to organochlorine pesticides for gestational hypertension (GH), preeclampsia (PE) and gestational diabetes mellitus (GDM). Chlordecone is a persistent organochlorine pesticide that was used intensively, and almost exclusively, in the French West Indies until 1993. We investigated the impact of prenatal exposure to chlordecone on the occurrence of GDM, GH and PE by studying 779 pregnant women enrolled in a prospective mother-child cohort (Timoun Study) in Guadeloupe between 2004 and 2007. Chlordecone exposure was determined by assaying maternal plasma and information about pregnancy complications was obtained from midwives, pediatricians and hospital medical records after delivery. The risks of GH (n=65), PE (n=31) and GDM (n=71) were estimated by multiple logistic regression including potential confounders. Levels of chlordecone plasma concentration in the third (OR=0.2; 95% confidence interval (CI): 0.1, 0.5) and fourth quartiles (OR=0.3; 95% CI: 0.2, 0.7) were associated with a statistically significant decrease in the risk of GH. A log10 increase in chlordecone concentration was significantly associated with lower risk of GH (OR=0.4; 95% CI: 0.2, 0.6). No significant associations were observed between the chlordecone exposure and the risk of PE or GDM. This study suggests an inverse association between chlordecone exposure during pregnancy and GH. Further studies are required to determine the underlying mechanism, or the potential unknown confounding factors, resulting in this association.
ISSN: 0160-4120

hal-01061391
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01061391
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01061391/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01061391/file/Saunders_et_al._Final_version_main_manuscript.pdf
DOI : 10.1016/j.envint.2014.03.024

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
BACKGROUND: Studies relating long-term exposure to persistent organochlorine pollutants (POPs) with endocrine activities (endocrine disrupting chemicals) on circulating levels of steroid hormones have been limited to a small number of hormones and reported conflicting results. OBJECTIVE: We examined the relationship between serum concentrations of dehydroepiandrosterone, dehydroepiandrosterone sulphate, androstenedione, androstenediol, testosterone, free and bioavailable testosterone, dihydrotestosterone, estrone, estrone sulphate, estradiol, sex-hormone binding globulin, follicle-stimulating hormone, and luteinizing hormone as a function of level of exposure to three POPs known to interfere with hormone-regulated processes in different way: dichlorodiphenyl dichloroethene (DDE), polychlorinated biphenyl (PCB) congener 153, and chlordecone. METHODS: We collected fasting, morning serum samples from 277 healthy, non obese, middle-aged men from the French West Indies. Steroid hormones were determined by gas chromatography-mass spectrometry, except for dehydroepiandrosterone sulphate, which was determined by immunological assay, as were the concentrations of sex-hormone binding globulin, follicle-stimulating hormone and luteinizing hormone. Associations were assessed by multiple linear regression analysis, controlling for confounding factors, in a backward elimination procedure, in multiple bootstrap samples. RESULTS: DDE exposure was negatively associated to dihydrotestosterone level and positively associated to luteinizing hormone level. PCB 153 was positively associated to androstenedione and estrone levels. No association was found for chlordecone. CONCLUSIONS: These results suggested that the endocrine response pattern, estimated by determining blood levels of steroid hormones, varies depending on the POPs studied, possibly reflecting differences in the modes of action generally attributed to these compounds. It remains to be investigated whether this response pattern is predictive of the subsequent occurrence of disease.
ISSN: 1932-6203

hal-00876025
https://hal.archives-ouvertes.fr/hal-00876025
https://hal.archives-ouvertes.fr/hal-00876025/document
https://hal.archives-ouvertes.fr/hal-00876025/file/Persistent_Organochlorine-accepted.pdf
DOI : 10.1371/journal.pone.0066460

Éditeur(s) : HAL CCSD American College of Physicians
Résumé : International audience
BACKGROUND: Most clinical guidelines recommend that AIDS-free, HIV-infected persons with CD4 cell counts below 0.350 × 10(9) cells/L initiate combined antiretroviral therapy (cART), but the optimal CD4 cell count at which cART should be initiated remains a matter of debate. OBJECTIVE: To identify the optimal CD4 cell count at which cART should be initiated. DESIGN: Prospective observational data from the HIV-CAUSAL Collaboration and dynamic marginal structural models were used to compare cART initiation strategies for CD4 thresholds between 0.200 and 0.500 × 10(9) cells/L. SETTING: HIV clinics in Europe and the Veterans Health Administration system in the United States. PATIENTS: 20, 971 HIV-infected, therapy-naive persons with baseline CD4 cell counts at or above 0.500 × 10(9) cells/L and no previous AIDS-defining illnesses, of whom 8392 had a CD4 cell count that decreased into the range of 0.200 to 0.499 × 10(9) cells/L and were included in the analysis. MEASUREMENTS: Hazard ratios and survival proportions for all-cause mortality and a combined end point of AIDS-defining illness or death. RESULTS: Compared with initiating cART at the CD4 cell count threshold of 0.500 × 10(9) cells/L, the mortality hazard ratio was 1.01 (95% CI, 0.84 to 1.22) for the 0.350 threshold and 1.20 (CI, 0.97 to 1.48) for the 0.200 threshold. The corresponding hazard ratios were 1.38 (CI, 1.23 to 1.56) and 1.90 (CI, 1.67 to 2.15), respectively, for the combined end point of AIDS-defining illness or death. Limitations: CD4 cell count at cART initiation was not randomized. Residual confounding may exist. CONCLUSION: Initiation of cART at a threshold CD4 count of 0.500 × 10(9) cells/L increases AIDS-free survival. However, mortality did not vary substantially with the use of CD4 thresholds between 0.300 and 0.500 × 10(9) cells/L.
ISSN: 0003-4819

hal-00875307
https://hal.archives-ouvertes.fr/hal-00875307
PUBMED : 21502648
DOI : 10.7326/0003-4819-154-8-201104190-00001

Éditeur(s) : HAL CCSD John Libbey Eurotext
Résumé : International audience
Prostate cancer is the most frequent cancer affecting men in most Western countries. Certain risk factors have been identified (age, family history, ethnic origin), but the aetiology of this cancer remains largely unknown. However, a role for environmental factors is strongly suspected. Questions have been raised concerning the role of the chemical substances generated by human activities in the occurrence of this disease. Diverse studies have consistently demonstrated a higher risk of prostate cancer in agricultural populations than in the general population. The hypothesis that this higher risk is linked to the use of pesticides has been tested in a number of studies, mostly in North America and Europe. However, to date, with a few possible exceptions, it has been impossible to demonstrate a significant association between exposure to pesticides or a chemical family of pesticides and prostate cancer. In the face of these uncertainties, rigorous studies are required, with objective measurements of exposure, taking into account confounding factors and individual risk factors, making it possible to assess gene-environment interactions.
ISSN: 0007-4551

inserm-00504733
http://www.hal.inserm.fr/inserm-00504733
DOI : 10.1684/bdc.2008.0812
PUBMED : 19258224

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Despite the dramatic reductions in children's blood lead levels (BLLs), there is considerable evidence that low-level lead exposure is associated with intellectual deficits and behavioral problems, without apparent threshold. There are limited data, however, about the contribution of residential sources of lead to contemporary children's blood lead levels. The aim of this study is to calculate the contributions of residential sources of lead to assess the potential impact of setting new standards for lead levels in residential dust, soil and water. We enrolled 484 French children aged from 6 months to 6 years, and collected data on social, housing and individual characteristics. Lead concentrations in blood and environmental samples (water, soils, and dusts) were measured using inductively coupled plasma mass spectrometry. Data were analyzed using a multivariate generalized additive model accounting for the sampling design and the sampling weights. We found that exceedingly low concentrations of lead in dust, soil and water were significant predictors of children's BLLs, after adjustment for potential confounding variables. Lead-contaminated floor dust was the main source of lead in blood. BLLs (GM: 14μg/L) increased by 65%, 13%, 25%, and 5% when lead content in floor dust, loose soil, hard soil and water increased from their 25th percentile to their 95th percentile, respectively. We also observed that the steepest increase in BLLs occurred at the lowest levels of lead-contaminated floor dust, which indicates that lead contamination should be kept as low as possible. Impact of different possible standards on children's BLLs was also tabulated and indicated that unless standards are set low, they will only benefit a small proportion of children who have the highest exposures.
ISSN: 1438-4639

inserm-00821999
http://www.hal.inserm.fr/inserm-00821999
DOI : 10.1016/j.ijheh.2013.02.007
PUBMED : 23528234

Éditeur(s) : HAL CCSD Elsevier Elsevier Masson
Résumé : International audience
Prostate cancer is the most frequent cancer affecting men in most Western countries. Certain risk factors have been identified (age, family history, ethnic origin), but the aetiology of this cancer remains largely unknown. However, a role for environmental factors is strongly suspected. Questions have been raised concerning the role of the chemical substances generated by human activities in the occurrence of this disease. Diverse studies have consistently demonstrated a higher risk of prostate cancer in agricultural populations than in the general population. The hypothesis that this higher risk is linked to the use of pesticides has been tested in a number of studies, mostly in North America and Europe. However, to date, with a few possible exceptions, it has been impossible to demonstrate a significant association between exposure to pesticides or a chemical family of pesticides and prostate cancer. Studies have also been carried out on the role of exposure to trace metals, such as cadmium, or to pollutants from industry, such as polychlorobiphenyls. However, no firm conclusions have been drawn. Finally, the effect of chemical substances with endocrine disruptor activity on the occurrence of prostate cancer remains largely unexplored in epidemiological studies. In the face of these uncertainties, rigorous studies are required, with objective measurements of exposure, taking into account confounding factors and individual risk factors, making it possible to assess gene-environment interactions.
ISSN: 1297-9589

inserm-00524579
http://www.hal.inserm.fr/inserm-00524579
DOI : 10.1016/j.gyobfe.2008.07.005
PUBMED : 18693059

Éditeur(s) : HAL CCSD
Résumé : International audience
Many emerging infectious diseases are caused by generalist pathogens that infect and transmit via multiple host species with multiple dissemination routes, thus confounding the understanding of pathogen transmission pathways from wildlife reservoirs to humans. The emergence of these pathogens in human populations has frequently been associated with global changes, such as socio-economic, climate or biodiversity modifications, by allowing generalist pathogens to invade and persist in new ecological niches, infect new host species, and thus change the nature of transmission pathways. Using the case of Buruli ulcer disease, we review how land-use changes, climatic patterns and biodiversity alterations contribute to disease emergence in many parts of the world. Here we clearly show that Mycobacterium ulcerans is an environmental pathogen characterized by multi-host transmission dynamics and that its infectious pathways to humans rely on the local effects of global environmental changes. We show that the interplay between habitat changes (for example, deforestation and agricultural land-use changes) and climatic patterns (for example, rainfall events), applied in a local context, can lead to abiotic environmental changes and functional changes in local biodiversity that favor the pathogen’s prevalence in the environment and may explain disease emergence.
ISSN: 2222-1751

Droits : http://creativecommons.org/licenses/by/
hal-01528488
http://hal.upmc.fr/hal-01528488
http://hal.upmc.fr/hal-01528488/document
http://hal.upmc.fr/hal-01528488/file/emi20177a.pdf
DOI : 10.1038/emi.2017.7