Publications by authors named "Stéphane Maillard"

14 Publications

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Dietary habits during the 2 months following the Chernobyl accident and differentiated thyroid cancer risk in a population-based case-control study.

Cancer Epidemiol 2018 02 8;52:142-147. Epub 2018 Jan 8.

Inserm, Center for Research in Epidemiology and Population Health (CESP), U1018, Radiation Epidemiology Group, Villejuif, F-94805, France; Gustave Roussy, Villejuif, F-94805, France; University of Paris-Sud, Villejuif, F-94800, France. Electronic address:

Background: The Chernobyl nuclear power plant accident occurred in Ukraine on April 26th 1986. In France, the radioactive fallout and thyroid radiation doses were much lower than in highly contaminated areas. However, a number of risk projections have suggested that a small excess in differentiated thyroid cancer (DTC) might occur in eastern France due to this low-level fallout. In order to investigate this potential impact, a case-control study on DTC risk factors was started in 2005, focusing on cases who were less than 15 years old at the time of the Chernobyl accident. Here, we aim to evaluate the relationship between some specific reports of potentially contaminated food between April and June 1986 - in particular fresh dairy products and leafy vegetables - and DTC risk.

Methods: After excluding subjects who were not born before the Chernobyl accident, the study included 747 cases of DTC matched with 815 controls. Odds ratios were calculated using conditional logistic regression models and were reported for all participants, for women only, for papillary cancer only, and excluding microcarcinomas.

Results: The DTC risk was slightly higher for participants who had consumed locally produced leafy vegetables. However, this association was not stronger in the more contaminated areas than in the others. Conversely, the reported consumption of fresh dairy products was not statistically associated with DTC risk.

Conclusion: Because the increase in DTC risk associated with a higher consumption of locally produced vegetables was not more important in the most contaminated areas, our study lacked power to provide evidence for a strong association between consumption of potentially contaminated food and DTC risk.
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http://dx.doi.org/10.1016/j.canep.2017.12.015DOI Listing
February 2018

FOXE1 Polymorphism Interacts with Dietary Iodine Intake in Differentiated Thyroid Cancer Risk in the Cuban Population.

Thyroid 2016 12 27;26(12):1752-1760. Epub 2016 Oct 27.

1 Cancer and Radiations, Center for Research in Epidemiology and Population Health (CESP) - U1018, French National Institute of Health and Medical Research (INSERM), Villejuif, France .

Background: The incidence of differentiated thyroid cancer (DTC) is low in Cuba, and the contribution of dietary factors to DTC in this population has not been investigated so far. The aim of this study was to evaluate the relationship between dietary iodine intake and DTC with regard to the interaction with environmental factors or some common single nucleotide polymorphisms (SNPs), based on a case-control study carried out in Cuba.

Methods: A total of 203 cases and 212 controls from the general population were interviewed face-to-face using the dietary intake questionnaire and the photo booklet from the E3N cohort. A specific food composition table was constructed for this study. For each parameter studied, the odds ratio (OR) was stratified on age group and sex, and further adjusted for dietary energy, smoking status, ethnic group, level of education, number of pregnancies, and body surface area.

Results: The risk of DTC was significantly reduced with increasing consumption of fish (p = 0.04), but no association between total dietary iodine intake and DTC risk was evident (p = 0.7). This lack of significant association was true whatever the age, the smoking status, the dietary selenium intake, and the ethnicity (p > 0.05). DTC risk was positively and strongly associated with the number of copies in the minor allele (A) for SNP rs965513 near FOXE1 among people who consumed less iodine than the median (p = 0.005).

Conclusion: Overall, the majority of the studied population had an optimal dietary iodine intake. DTC risk was inversely associated with high fish consumption. Furthermore, DTC risk was positively associated with the number of copies in the minor allele (A) of rs965513 among people who consumed less iodine than the median. Because these findings are based on post-diagnostic measures, studies with pre-diagnostic dietary iodine are needed for confirmation.
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http://dx.doi.org/10.1089/thy.2015.0594DOI Listing
December 2016

Recreational Physical Activity and Differentiated Thyroid Cancer Risk: A Pooled Analysis of Two Case-Control Studies.

Eur Thyroid J 2016 Jul 21;5(2):132-8. Epub 2016 May 21.

U1018, Centre d'Epidémiologie et de Santé des Populations (CESP), Institut National de la Santé et de la Recherche Médicale (INSERM), Villejuif, France; Institut Gustave Roussy, Villejuif, France; Université Paris-Saclay, Villejuif, France.

Purpose: Physical activity has been hypothesized to influence cancer occurrence through several mechanisms. To date, its relation with thyroid cancer risk has been examined in relatively few studies. We pooled 2 case-control studies conducted in Cuba and Eastern France to assess the relationship between self-reported practice of recreational physical activity since childhood and thyroid cancer risk.

Methods: This pooled study included 1,008 cases of differentiated thyroid cancer (DTC) matched with 1,088 controls (age range 9-35 and 17-60 years in the French and Cuban studies, respectively). Risk factors associated with the practice of recreational physical activity were estimated using OR and 95% CI. Logistic regressions were stratified by age class, country, and gender and were adjusted for ethnic group, level of education, number of pregnancies for women, height, BMI, and smoking status.

Results: Overall, the risk of thyroid cancer was slightly reduced among subjects who reported recreational physical activity (OR = 0.8; 95% CI 0.5-1.0). The weekly frequency (i.e. h/week) seems to be more relevant than the duration (years).

Conclusion: Long-term recreational physical activity, practiced since childhood, may reduce the DTC risk. However, the mechanisms whereby the DTC risk decreases are not yet entirely clear.
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http://dx.doi.org/10.1159/000445887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4949366PMC
July 2016

Anthropometric Risk Factors for Differentiated Thyroid Cancer in Young Men and Women From Eastern France: A Case-Control Study.

Am J Epidemiol 2015 Aug 30;182(3):202-14. Epub 2015 Jun 30.

The incidence of thyroid cancer has risen over the past decade, along with a rise in obesity. We studied the role of anthropometric risk factors for differentiated thyroid cancer at the time of diagnosis and at age 20 years in a case-control study conducted in eastern France between 2005 and 2010. The study included 761 adults diagnosed with differentiated thyroid cancer before 35 years of age between 2002 and 2006. They were matched with 825 controls from the general population. Odds ratios were calculated using conditional logistic regression models and were reported for all participants, those with papillary cancer only, and women only. The risk of thyroid cancer was higher for participants with a high body surface area (BSA), great height, or excess weight and for women with a high body fat percentage. Conversely, no significant association was found between body mass index and the risk of thyroid cancer. In the present study, we provide further evidence of the role of BSA and excess weight in the risk of thyroid cancer. These epidemiologic observations should be confirmed by further exploration of the biological mechanisms responsible for the associations of obesity and BSA with thyroid cancer.
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http://dx.doi.org/10.1093/aje/kwv048DOI Listing
August 2015

Thyroid volume and its relation to anthropometric measures in a healthy cuban population.

Eur Thyroid J 2015 Mar 26;4(1):55-61. Epub 2015 Feb 26.

Radiation Epidemiology Group, Unit 1018-Inserm, Villejuif, France ; The Gustave Roussy Cancer Center, Villejuif, France ; Paris-Sud University, Villejuif, France.

Objectives: The aim of this study was to describe the thyroid volume in healthy adults by ultrasound and to correlate this volume with some anthropometric measures and other differentiated thyroid cancer risk factors.

Study Design: Thyroid volume and anthropometric measures were recorded in a sample of 100 healthy adults, including 21 men and 79 women aged 18-50 years, living in a non-iodine-deficient area of Havana city.

Results: The average thyroid volume was 6.6 ± 0.26 ml; it was higher in men (7.3 ml) than in women (6.4 ml; p = 0.15). In the univariate analysis, thyroid volume was correlated with all anthropometric measures, but in the multivariate analysis, body surface area was found to be the only significant anthropometric parameter. Thyroid volume was also higher in current or former smokers and in persons with blood group AB or B.

Conclusion: Specific reference values of thyroid volume as a function of body surface area could be used for evaluating thyroid volume in clinical practice. The relation between body surface area and thyroid volume is coherent with what is known about the relation of thyroid volume to thyroid cancer risk, but the same is not true about the relation between thyroid volume and smoking habit.
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http://dx.doi.org/10.1159/000371346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4404892PMC
March 2015

Common variants at the 9q22.33, 14q13.3 and ATM loci, and risk of differentiated thyroid cancer in the Cuban population.

BMC Genet 2015 Mar 1;16:22. Epub 2015 Mar 1.

The French National Institute of Health and Medical Research (Inserm), Centre for Research in Epidemiology and Population Health (CESP), U1018, Radiation Epidemiology Group, Villejuif, 94805, France.

Background: The incidence of differentiated thyroid carcinoma (DTC) in Cuba is low and the contribution of host genetic factors to DTC in this population has not been investigated so far. Our goal was to assess the role of known risk polymorphisms in DTC cases living in Havana. We genotyped five polymorphisms located at the DTC susceptibility loci on chromosome 14q13.3 near NK2 homeobox 1 (NKX2-1), on chromosome 9q22.33 near Forkhead factor E1 (FOXE1) and within the DNA repair gene Ataxia-Telangiectasia Mutated (ATM) in 203 cases and 212 age- and sex- matched controls. Potential interactions between these polymorphisms and other DTC risk factors such as body surface area, body mass index, size, ethnicity, and, for women, the parity were also examined.

Results: Significant association with DTC risk was found for rs944289 near NKX2-1 (OR per A allele = 1.6, 95% CI: 1.2-2.1), and three polymorphisms near or within FOXE1, namely rs965513 (OR per A allele = 1.7, 95% CI: 1.2-2.3), rs1867277 in the promoter region of the gene (OR per A allele = 1.5, 95% CI: 1.1-1.9) and the poly-alanine tract expansion polymorphism rs71369530 (OR per Long Allele = 1.8, 95% CI: 1.3-2.5), only the 2 latter remaining significant when correcting for multiple tests. Overall, no association between DTC and the coding SNP D1853N (rs1801516) in ATM (OR per A Allele = 1.1, 95% CI: 0.7-1.7) was seen. Nevertheless women who had 2 or more pregnancies had a 3.5-fold increase in risk of DTC if they carried the A allele (OR 3.5, 95% CI: 3.2-9.8) as compared to 0.8 (OR 0.8, 95% CI: 0.4-1.6) in those who had fewer than 2.

Conclusions: We confirmed in the Cuban population the role of the loci previously associated with DTC susceptibility in European and Japanese populations through genome-wide association studies. Our results on ATM and the number of pregnancies raise interesting questions on the mechanisms by which oestrogens, or other hormones, alter the DNA damage response and DNA repair through the regulation of key effector proteins such as ATM. Due to the small size of our study and to multiple tests, all these results warrant further investigation.
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http://dx.doi.org/10.1186/s12863-015-0180-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4354996PMC
March 2015

Common variants at 9q22.33, 14q13.3, and ATM loci, and risk of differentiated thyroid cancer in the French Polynesian population.

PLoS One 2015 7;10(4):e0123700. Epub 2015 Apr 7.

Inserm, Centre for research in Epidemiology and Population Health (CESP), U1018, Radiation Epidemiology Group, F-94800, Villejuif, France; University Paris-Sud, UMRS 1018, F-94807, Villejuif, France; IGR, F-94800, Villejuif, France.

Background: French Polynesia has one of the highest incidence rates of thyroid cancer worldwide. Relationships with the atmospheric nuclear weapons tests and other environmental, biological, or behavioral factors have already been reported, but genetic susceptibility has yet to be investigated. We assessed the contribution of polymorphisms at the 9q22.33 and 14q13.3 loci identified by GWAS, and within the DNA repair gene ATM, to the risk of differentiated thyroid cancer (DTC) in 177 cases and 275 matched controls from the native population.

Principal Findings: For the GWAS SNP rs965513 near FOXE1, an association was found between genotypes G/A and A/A, and risk of DTC. A multiplicative effect of allele A was even noted. An excess risk was also observed in individuals carrying two long alleles of the poly-alanine tract expansion in FOXE1, while no association was observed with rs1867277 falling in the promoter region of the gene. In contrast, the GWAS SNP rs944289 (NKX2-1) did not show any significant association. Although the missense substitution D1853N (rs1801516) in ATM was rare in the population, carriers of the minor allele (A) also showed an excess risk. The relationships between these five polymorphisms and the risk of DTC were not contingent on the body surface area, body mass index, ethnicity or dietary iodine intake. However, an interaction was evidenced between the thyroid radiation dose and rs944289.

Significance: A clear link could not be established between the high incidence in French Polynesia and the studied polymorphisms, involved in susceptibility to DTC in other populations. Important variation in allele frequencies was observed in the Polynesian population as compared to the European populations. For FOXE1 rs965513, the direction of association and the effect size was similar to that observed in other populations, whereas for ATM rs1801516, the minor allele was associated to an increased risk in the Polynesian population and with a decreased risk in the European population.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0123700PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4388539PMC
April 2016

Environmental, lifestyle, and anthropometric risk factors for differentiated thyroid cancer in cuba: a case-control study.

Eur Thyroid J 2014 Sep 28;3(3):189-96. Epub 2014 Aug 28.

Radiation Epidemiology Group, 1018 INSERM Unit, Villejuif, France ; Institut Gustave Roussy, Villejuif, France ; University Paris-Sud, Villejuif, France.

Background: The incidence of differentiated thyroid carcinoma (DTC) is low in people of African origin and higher in populations living on islands, but there is no well-established explanation for these differences. Cuba is a multiethnic nation with people of African and Spanish descent. Until now, no study on the risk factors of DTC has focused on the Cuban population. Our aim is to establish the role of environmental and lifestyle factors and to relate anthropometric measurements to the risk of developing DTC in Cuba.

Methods: We performed a case-control study of 203 DTC patients treated in two hospitals in Havana and 212 controls living in the area covered by these hospitals (i.e. parts of Havana and the municipality of Jaruco). Risk factors were analyzed using conditional logistic regression.

Results: As has been shown by other studies, we found that non-African ethnicity, never smoking, parity, and high body mass index are risk factors significantly associated with DTC, whereas a history of exposure to ionizing radiation and level of education were not significantly related with disease development. Being rhesus factor-positive, having a personal history of benign thyroid disorder, agricultural occupation, and consumption of artesian well water were also associated with a significantly increased risk of developing DTC.

Conclusions: The original findings reported here concern the risk of DTC that was associated with non-African ethnicity, positive rhesus factor, farming, and drinking water from an artesian well.
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http://dx.doi.org/10.1159/000362928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4224259PMC
September 2014

Menstrual and reproductive factors in the risk of differentiated thyroid carcinoma in young women in France: a population-based case-control study.

Am J Epidemiol 2014 Nov 30;180(10):1007-17. Epub 2014 Sep 30.

The incidence of thyroid cancer has increased in eastern Europe since the Chernobyl nuclear power plant accident. Although the radioactive fallout was much less severe and the thyroid radiation dose was much lower in France, a case-control study was initiated in eastern France. The present study included 633 young women who were diagnosed with differentiated thyroid cancer before 35 years of age between 2002 and 2006 and matched with 677 controls. Face-to-face interviews were conducted from 2005 to 2010. Odds ratios were calculated using conditional logistic regressions and were reported in the total group and by histopathological type of cancer ("only papillary" and "excluding microcarcinomas"). The risk of thyroid cancer was higher in women who had a higher number of pregnancies, used a lactation suppressant, or had early menarche. Conversely, breastfeeding, oral contraceptive use, and late age at first pregnancy were associated with a lower risk of thyroid cancer. No association was observed between thyroid cancer and having irregular menstrual cycle, undergoing treatment for menstrual cycle regularity shortly after menarche, having a cessation of menstruation, use of another contraceptive, history of miscarriage or abortion for the first pregnancy, or having had gestational diabetes. This study confirms the role of hormonal and reproductive factors in thyroid cancer, and our results support the fact that exposure to estrogens increases thyroid cancer risk.
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http://dx.doi.org/10.1093/aje/kwu220DOI Listing
November 2014

Determination of total iodine in French Polynesian foods: method validation and occurrence data.

Food Chem 2015 Feb 7;169:134-40. Epub 2014 Aug 7.

University of Paris-Est, Anses, Maisons-Alfort Laboratory for Food Safety, Department of Chemical Contaminants in Food, Metallic Trace Elements and Minerals Unit, Maisons-Alfort, France. Electronic address:

Pacific Island populations show some of the highest incidences of thyroid cancer in the world, and iodine deficiency is suspected to play a role. Iodine content was determined in 124 different French Polynesian food samples using inductively coupled plasma-mass spectrometry after alkaline digestion. For samples containing starch, the method was optimised by including an additional enzymatic treatment step. This analytical method was validated with an accuracy profile approach, using certified reference materials with iodine contents ranging from 0.027 to 4.95mgiodinekg(-1) dry weight. The trueness bias ranged from -5.8% to 22.4% and the highest observed intermediate precision coefficient of variation CVR was 11% in starchy materials. Tested Polynesian foods showed large variation in iodine content, with values of 0.014-0.032mgkg(-1) for fruits, 0.014-0.081mgkg(-1) for starchy samples, 0.027-1.85mgkg(-1) for green vegetables, 0.222-5.19mgkg(-1) for fish, 6.51-85.6mgkg(-1) for shellfish, and 0.004-1.39mgkg(-1) for beverages.
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http://dx.doi.org/10.1016/j.foodchem.2014.07.142DOI Listing
February 2015

Lack of association between fingernail selenium and thyroid cancer risk: a case-control study in French Polynesia.

Asian Pac J Cancer Prev 2014 ;15(13):5187-94

Radiation Epidemiology Group, Centre for Research in Epidemiology and Population Health (CESP), UMR 1018 Inserm, France E-mail

Background: Numerous studies have suggested that selenium deficiency may be associated with an increased risk for several types of cancer, but few have focused on thyroid cancer.

Materials And Methods: We examined the association between post-diagnostic fingernail selenium levels and differentiated thyroid cancer risk in a French Polynesian matched case-control study. Conditional logistic regression models were used to estimate odds ratios and 95% confidence intervals.

Results: The median selenium concentration among controls was 0.76 μg/g. Significantly, we found no association between fingernail selenium levels and thyroid cancer risk after conditioning on year of birth and sex and additionally adjusting for date of birth (highest versus lowest quartile: odds-ratio=1.12, 95% confidence interval: 0.66-1.90; p-trend=0.30). After additional adjustment for other covariates, this association remained non-significant (p-trend=0.60). When restricting the analysis to thyroid cancer of 10 mm or more, selenium in nails was non-significantly positively linked to thyroid cancer risk (p-trend=0.09). Although no significant interaction was evidenced between iodine in nails and selenium in nails effect (p=0.70), a non-significant (p-trend =0.10) positive association between selenium and thyroid cancer risk was seen in patients with less than 3 ppm of iodine in nails. The highest fingernail selenium concentration in French Polynesia was in the Marquises Islands (M=0.87 μg/g) and in the Tuamotu-Gambier Archipelago (M=0.86 μg/g).

Conclusions: Our results do not support, among individuals with sufficient levels of selenium, that greater long-term exposure to selenium may reduce thyroid cancer risk. Because these findings are based on post-diagnostic measures, studies with prediagnostic selenium are needed for corroboration.
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http://dx.doi.org/10.7314/apjcp.2014.15.13.5187DOI Listing
April 2015

Differentiated thyroid carcinoma risk factors in French Polynesia.

Asian Pac J Cancer Prev 2014 ;15(6):2675-80

Inserm, Centre for Research in Epidemiology and Population Health (CESP), U1018, Radiation Epidemiology Group, Villejuif, France E-mail :

Background: To investigate differentiated thyroid cancer risk factors in natives of French Polynesia is of interest because of the very high incidence of this cancer in the archipelago.

Materials And Methods: To assess the role of various potential risk factors of thyroid cancer in the natives of French Polynesia we performed a case-control study. The study included almost all the French Polynesians diagnosed with differentiated thyroid carcinoma between 1981 and 2003 (n=229) and 373 French Polynesian control individuals from the general population without cancer.

Results: Thyroid radiation dose received from nuclear fallout before the age of 15, a personal history of neck or/and head medical irradiation, obesity, tallness, large number of children, an artificial menopause, a familial history of thyroid cancer, a low dietary iodine intake, and having a spring as the main source of drinking water were found to be significant risk factors. No roles of smoking habits, alcohol consumption, iodine containing drugs, and exposure to pesticides were evidenced.

Conclusions: Except for smoking, differentiated thyroid carcinoma risk factors in natives of French Polynesia are similar to those in other populations. Our finding on the role of having a spring as a drinking water origin is coherent with some other studies and could be due to geological factors.
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http://dx.doi.org/10.7314/apjcp.2014.15.6.2675DOI Listing
January 2015

[Nuclear, radiological, biological, and chemical dangers and risks].

Ther Umsch 2008 Jan;65(1):43-8

Departement für Verteidigung, Bevölkerungsschutz und Sport VBS, Kompetenzzentrum ABC der Armee, ABC Zentrum, Spiez.

In contrast to military conflicts natural events, industrial disasters as well as terror attacks can surprise our society without warning. In all these events nuclear, radiological, biological or chemical dangers can be involved as well. The acute or retarded health effects on the public, first responders and society are well known. The psychological strain and disconcertion have also to be considered as well. Conditions to respond to these events with success are the early recognition and introduction of appropriate immediate measures. The early recognition is as such important because these events don't only have to start with an explosion. The early recognition should maybe base on the delayed appearance of atypical symptoms or with the increase of rare illnesses. The response to some incidence will inevitable includes drastical safety precautions such as evacuations, limitations of passenger traffic or food consumption. Precautions will only be carried out if they are understood by the public. Objective information and sensiblisation of the public and all concerned by this matter is crucial; without minimization or paranoia.
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http://dx.doi.org/10.1024/0040-5930.65.1.43DOI Listing
January 2008

Delayed transport of tissue-nonspecific alkaline phosphatase with missense mutations causing hypophosphatasia.

Eur J Med Genet 2007 Sep-Oct;50(5):367-78. Epub 2007 Jul 21.

Equipe Structure-Fonction et Génétique, EA 2493, CHU Paris Ile de France Ouest, Université de Versailles-Saint Quentin en Yvelines, France.

Hypophosphatasia is a rare genetic disease characterized by diminished bone and tooth mineralization due to deficient activity of tissue-nonspecific alkaline phosphatase (TNSALP). The disease is clinically heterogeneous due to different mutations in the TNSALP gene. In order to determine whether mutated TNSALP proteins may be sequestered, degraded, or subjected to delay in their transport to the cell membrane, we built a plasmid expressing a YFP-TNSALP fluorescent fusion protein allowing the observation of cellular localization in live cells by fluorescence confocal microscopy at different time points after transfection. We studied five mutants (c. 571G>A, c. 653T>C, c. 746G>T, c. 1363G>A and c. 1468A>T) exhibiting various levels of in vitro residual enzymatic activity. While the wild-type protein reached the membrane within the first 24h after transfection, the mutants reached the membrane with delays of 24, 48 or 72 h. For all of the tested mutations, accumulation of the mutated proteins, mainly in the Golgi apparatus, was observed. We concluded that reduced ALP activity of these TNSALP mutants results from structural disturbances and delay in membrane anchoring, and not from compromised catalytic activity.
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http://dx.doi.org/10.1016/j.ejmg.2007.06.005DOI Listing
November 2007