BACKGROUND: The Problematic Internet use among adolescents is an increasingly discussed topic in connection with the continuous development of technologies. If it enters to the period of adolescent age factor of hematoncological disease, which requires long term tratment and isolation for a long time, the risk of growth of non-substance addictive behavior is likely to increase in this context. AIM: The main aim of the research was to find out the prevalence of Problematic Internet use in a group of adolescent patients after the intensive cancer treatment within the Department of Pediatric Hematology and Oncology of the University Hospital in Motol (KDHO). Another aim was to map specific characteristics that may be a predictor of later risk behavior and to find out possible correlation between these characteristics and problematic Internet use. METHODS: The concept of the research is based on quantitative methods of epidemiological cases and controls study. The data were collected through a screening questionnaire survey using a compilation of a short version of the Problematic Internet Use Questionnaire (PIU Q- SF 6) and Substance Use Risk Profile (SURPS) personality traits). Data were evaluated using descriptive statistics and the χ2 test. The p value p < 0,05 was determined as statistically...

En 2007, le Centre International de Recherche sur le Cancer (CIRC) a classé le “travail de nuit entrainant une perturbation du rythme circadien” comme probablement cancérogène pour l'homme (groupe 2A) sur la base de preuves suffisantes chez l’animal mais limitées chez l'Homme. A ce jour, peu d’études se sont intéressées au rôle du travail de nuit et des gènes de l’horloge dans la survenue du cancer de la prostate. Dans ce contexte, nous avons étudié le rôle du travail de nuit, des gènes circadiens ainsi que leurs interactions dans le risque de cancer de la prostate, à partir des données d’EPICAP, étude cas-témoins réalisée en population générale), incluant 819 cas et 879 témoins. Un questionnaire standardisé a permis de recueillir des informations détaillées sur le travail de nuit, qu’il soit fixe ou rotatif. La réalisation d’un prélèvement biologique a permis un génotypage de l’ADN pour l’étude des gènes de l’horloge. Globalement, nous n’avons pas mis en évidence d’association entre le travail de nuit et le cancer de la prostate quelle que soit l'agressivité du cancer de la prostate, alors que nous avons observé une augmentation du risque chez les hommes ayant un chronotype du soir. Une durée d’exposition d’au moins 20 ans au travail de nuit fixe associée au cancer de la prostate agressif et de manière plus prononcée en combinaison avec des nuits de longue durée (en moyenne de plus de 10 heures par nuit) ou avec un nombre maximal de nuits consécutives supérieur à 6. Nous avons observé une association significative avec le cancer de la prostate pour les gènes NPAS2 et PER1, alors que seul le gène RORA était significatif pour les cancers agressifs. L’analyse de l’interaction entre les gènes de l’horloge et le travail de nuit dans le risque de survenue de cancer de la prostate a révélé des interactions significatives avec les gènes RBX1, CRY1, NPAS2 et PRKAG2. Les résultats de notre étude renforcent l'hypothèse d'un lien entre le travail de nuit en tant que facteur de perturbation du rythme circadien et le risque de cancer de la prostate et fournissent également de nouvelles preuves d'un lien potentiel avec les variants des gènes de l’horloge. Ces résultats, pourraient contribuer à l’identification de nouveaux facteurs de risque modifiables pour le cancer de la prostate pouvant être accessibles à la prévention. Des recherches plus approfondies aideront à mieux cerner les mécanismes biologiques impliquant les gènes circadiens dans le développement du cancer de la prostate ainsi que leurs interactions avec le travail de nuit. / In 2007, the International Agency for Research on Cancer (IARC) classified "shift work leading to a disruption of circadian rhythm» as probably carcinogenic to humans (Group 2A) on the basis of sufficient evidence in animals but limited evidence in humans. To date, few studies have focused on the role of night work and clock genes in prostate cancer occurrence. In this context, we studied the role of night work, circadian genes and their interactions in prostate cancer risk, using data from EPICAP, a population-based case-control study, including 819 cases and 879 controls. A standardized questionnaire was used to collect detailed information on both fixed and rotating night work. Biological samples were also collected for DNA genotyping and for prostate cancer-clock genes association study. Overall, we did not find an association between night work and prostate cancer whatever the disease aggressiveness, while we observed an increased risk in men with an evening chronotype. At least 20 years of exposure to fixed night work was associated with aggressive prostate cancer and this was more stricken in combination with long nights (on average more than 10 hours per night shift) or more than 6 consecutive night shifts. We observed a significant association with prostate cancer for the clock genes NPAS2 and PER1, while only RORA was significant for aggressive cancers. We found significant interaction between clock genes and night work in the risk of prostate cancer for RBX1, CRY1, NPAS2 and PRKAG2. Our results provide support for the hypothesis that night work disrupting circadian rhythm could be associated with prostate cancer and they also provide new evidence of a potential link between clock genes variants and prostate cancer. These results may particularly contribute to the identification of new prostate cancer risk factors that could be modifiable and available for prevention. Further studies are warranted to better understand the biological mechanisms involving circadian genes in the development of prostate cancer and their interactions with night work.

The study area for this dissertation is Hamilton, Ontario, Canada. / The general theme of this dissertation is understanding and enabling safe walking routes to school for children. We restrict our focus to safety issues related to the motorized-transportation environment, thereby defining safety as a function of factors that determine whether or not a child will be struck by a motor-vehicle on their journey to or from school. Our analysis is unique because it is at a small geographical scale but is representative of an entire urban environment. Working at a small geographic scale allows us to evaluate the variability in safe routes for children within our study area and apply our findings to develop a decision support tool that could be used to plan individualized routes for children in other similar urban environments. Our study area for this dissertation is Hamilton, Ontario, Canada. The findings in this dissertation contribute ideas about how features of the local road environment may and may not influence risk of collisions between child pedestrians and motor-vehicles. It also offers methodological insight for future research on pedestrian safety at small geographic scales. This dissertation demonstrates the potential reduction in the risk of child pedestrian injuries by planning safer routes to school and also introduces methods that can be used to plan safer routes for children. Our results are a reminder of the importance of understanding the interaction between environment and behaviour in research on traffic safety and offer some caution to the notion of a universal 'safe route' to school. Whether or not a particular route to school is safe will very likely be dependent both on the environment and the child's behaviour in that environment. / Dissertation / Doctor of Social Science

Thèse en cotutelle internationale (Université Paris-Saclay) / Thesis completed under international cotutelle (Université Paris-Saclay) / CONTEXTE : Des résultats issus d'études sur les migrants suggèrent que les facteurs de risque environnementaux peuvent jouer un rôle dans la pathogenèse du cancer du sein, de l'ovaire et du poumon. Néanmoins, le rôle de ces facteurs dans l’étiologie de ces cancers reste mal connu. Les facteurs de risque professionnels chez les femmes ont été relativement peu étudiés malgré la proportion importante de la main-d'œuvre féminine à travers le monde. Peu d'études ont en effet examiné les professions fréquentes chez les femmes et les risques professionnels liés aux cancers féminins. OBJECTIFS : Etudier les associations entre 1) la profession, les expositions professionnelles et le cancer de l'ovaire, 2) les expositions professionnelles et le cancer du sein, et 3) la profession, les expositions professionnelles et le cancer du poumon. METHODES : Les données de trois études cas-témoins réalisées en population générale chez des femmes au Canada et en France qui disposaient d’informations sur l'historique professionnel ont été utilisées : l'étude PROVAQ sur le cancer de l'ovaire (491 cas, 897 témoins), l'étude CECILE sur le cancer du sein (1 206 cas, 1 294 témoins) et l'étude WELCA sur le cancer du poumon (731 cas, 751 témoins). Dans ces trois études, un hygiéniste industriel a codé la profession de chaque emploi de chaque participante. Les codes de profession ont été croisés avec une matrice emplois-expositions canadienne afin d’estimer les expositions professionnelles aux agents les plus répandus. La relation entre l'exposition à chacun des agents et le risque de cancer a été évaluée : 29 agents pour le cancer de l'ovaire, 49 agents pour le cancer du sein et 41 agents pour le cancer du poumon. Pour les cancers de l'ovaire et du poumon, les risques associés aux professions les plus fréquemment rencontrées ont également été étudiés. Les associations avec le risque de cancer pour les professions et les expositions professionnelles ont été estimées par régression logistique et en ajustant pour des facteurs de confusion, identifiés à l'aide de graphes acycliques dirigés. RESULTATS : Des risques accrus de cancer de l'ovaire ont été suggérés pour les professions dans le domaine de la comptabilité, de la vente, de la coiffure et de la couture, ainsi que pour les expositions aux agents chimiques utilisés dans les métiers de la coiffure. Pour le cancer du sein, les expositions professionnelles aux poussières de fibres textiles, aux solvants organiques, aux hydrocarbures aromatiques polycycliques, aux poussières de plastique et aux fumées de pyrolyse, étaient associées à des augmentations du risque. Les odds ratios différaient selon les sous-types de cancer du sein et en fonction du statut ménopausique pour certains agents. Pour le cancer du poumon, des odds ratios élevés ont été observés dans les métiers de l'enseignement, les professions libérales, chez les cols-blancs, la vente et les services. Des associations étaient également observées avec de nombreuses expositions professionnelles, en cohérence avec des études antérieures chez les femmes, telles que les fumées de cuisson, le formaldéhyde, les solvants organiques, les hydrocarbures aromatiques polycycliques, les métaux et les peintures/vernis. Les risques de cancer du poumon pour certains agents semblaient différer selon le statut tabagique. CONCLUSIONS : Certaines professions et expositions professionnelles peuvent être associées à des risques accrus de cancer de l'ovaire, du sein et du poumon chez les femmes. Du fait de la nature exploratoire du travail, d'autres recherches chez des femmes en population générale doivent être menées afin de confirmer ces résultats. Des études portant sur des échantillons plus importants et l’évaluation des expositions par experts, permettant d’utiliser des méthodes statiques avancées, pourraient être utiles pour identifier le rôle spécifique de certaines expositions professionnelles dans le risque de cancer. / BACKGROUND: Evidence from migrant studies suggests that environmental risk factors may play a role in the pathogenesis of breast, ovarian, and lung cancers, yet the etiology of these cancers remains poorly understood. Women account for a significant proportion of the labour force worldwide, yet research on occupational hazards of female workers is limited. Few studies have examined occupations common to women and occupational risks in relation to female cancers. OBJECTIVES: The specific objectives of the thesis were: 1) to study the association between occupation, occupational exposures and ovarian cancer, 2) to study the association between occupational exposures and breast cancer, and 3) to study the association between occupation, occupational exposures and lung cancer in women. METHODS: Data from three population-based case-control studies on women in Canada and France that collected occupational history information was used to achieve the objectives: the PROVAQ study on ovarian cancer (491 cases, 897 controls), the CECILE study on breast cancer (1,206 cases, 1,294 controls), and the WELCA study on lung cancer (731 cases, 751 controls). In all three studies, an industrial hygienist coded the occupation of each participant’s job. Job codes were linked to the Canadian job-exposure matrix, thereby generating exposure estimates for many agents. The relationship between exposure to each of the most prevalent agents and cancer risk was assessed, specifically 29 agents for ovarian cancer, 49 agents for breast cancer, and 41 agents for lung cancer. For ovarian and lung cancers, prevalent occupations were additionally examined by comparing participants employed in an occupation for <10 years and ≥10 years vs. never employed in the occupation. Associations with cancer risk for occupations and occupational exposures were estimated using logistic regression and adjusting for minimally sufficient confounder sets, identified using directed acyclic graphs. RESULTS: Excess ovarian cancer risks were suggested for accountancy, sales, hairdressing, and sewing occupations, and for occupational exposure to agents linked to hairdressing-related occupations. Interpretations of results for single agents were limited due to multiple correlated exposures. For breast cancer, occupational exposure to agents, particularly textile fibre dusts, organic solvents, polycyclic aromatic hydrocarbons, plastic dusts and pyrolysis fumes, were potentially associated with increased risks. Relative risks were suggested to differ among breast cancer subtypes and according to menopausal status for some agents. For lung cancer, elevated odds ratios were observed for teaching, professional, white-collar, sales, and service occupations, and for numerous occupational exposures, some of which were consistent with previous studies in women, such as cooking fumes, formaldehyde, organic solvents, polycyclic aromatic hydrocarbons, metals, and paints/varnishes. Lung cancer risks for some agents were suggested to differ by smoking status. CONCLUSIONS: Certain occupations and occupational exposures may be associated with excess ovarian, breast, and lung cancer risks in women. As many odds ratios observed were imprecise, further population-based research on women is warranted to replicate findings. Studies with larger sample sizes and expert assessment information that can perform more advanced statistical methods accounting for multiple exposures may be useful in disentangling the effects of correlated agents in the estimation of cancer risk.

No description available.

A variety of complex data has broadened in many research fields such as epidemiology, genomics, and analytical chemistry with the development of science, technologies, and design scheme over the past few decades. For example, in epidemiology, the matched case-crossover study design is used to investigate the association between the clustered binary outcomes of disease and a measurement error in covariate within a certain period by stratifying subjects' conditions. In genomics, high-correlated and high-dimensional(HCHD) data are required to identify important genes and their interaction effect over diseases. In analytical chemistry, multiple time series data are generated to recognize the complex patterns among multiple classes. Due to the great diversity, we encounter three problems in analyzing those complex data in this dissertation. We have then provided several contributions to semiparametric and nonparametric methods for dealing with the following problems: the first is to propose a method for testing the significance of a functional association under the matched study; the second is to develop a method to simultaneously identify important variables and build a network in HDHC data; the third is to propose a multi-class dynamic model for recognizing a pattern in the time-trend analysis. For the first topic, we propose a semiparametric omnibus test for testing the significance of a functional association between the clustered binary outcomes and covariates with measurement error by taking into account the effect modification of matching covariates. We develop a flexible omnibus test for testing purposes without a specific alternative form of a hypothesis. The advantages of our omnibus test are demonstrated through simulation studies and 1-4 bidirectional matched data analyses from an epidemiology study. For the second topic, we propose a joint semiparametric kernel machine network approach to provide a connection between variable selection and network estimation. Our approach is a unified and integrated method that can simultaneously identify important variables and build a network among them. We develop our approach under a semiparametric kernel machine regression framework, which can allow for the possibility that each variable might be nonlinear and is likely to interact with each other in a complicated way. We demonstrate our approach using simulation studies and real application on genetic pathway analysis. Lastly, for the third project, we propose a Bayesian focal-area detection method for a multi-class dynamic model under a Bayesian hierarchical framework. Two-step Bayesian sequential procedures are developed to estimate patterns and detect focal intervals, which can be used for gas chromatography. We demonstrate the performance of our proposed method using a simulation study and real application on gas chromatography on Fast Odor Chromatographic Sniffer (FOX) system. / Doctor of Philosophy / A variety of complex data has broadened in many research fields such as epidemiology, genomics, and analytical chemistry with the development of science, technologies, and design scheme over the past few decades. For example, in epidemiology, the matched case-crossover study design is used to investigate the association between the clustered binary outcomes of disease and a measurement error in covariate within a certain period by stratifying subjects' conditions. In genomics, high-correlated and high-dimensional(HCHD) data are required to identify important genes and their interaction effect over diseases. In analytical chemistry, multiple time series data are generated to recognize the complex patterns among multiple classes. Due to the great diversity, we encounter three problems in analyzing the following three types of data: (1) matched case-crossover data, (2) HCHD data, and (3) Time-series data. We contribute to the development of statistical methods to deal with such complex data. First, under the matched study, we discuss an idea about hypothesis testing to effectively determine the association between observed factors and risk of interested disease. Because, in practice, we do not know the specific form of the association, it might be challenging to set a specific alternative hypothesis. By reflecting the reality, we consider the possibility that some observations are measured with errors. By considering these measurement errors, we develop a testing procedure under the matched case-crossover framework. This testing procedure has the flexibility to make inferences on various hypothesis settings. Second, we consider the data where the number of variables is very large compared to the sample size, and the variables are correlated to each other. In this case, our goal is to identify important variables for outcome among a large amount of the variables and build their network. For example, identifying few genes among whole genomics associated with diabetes can be used to develop biomarkers. By our proposed approach in the second project, we can identify differentially expressed and important genes and their network structure with consideration for the outcome. Lastly, we consider the scenario of changing patterns of interest over time with application to gas chromatography. We propose an efficient detection method to effectively distinguish the patterns of multi-level subjects in time-trend analysis. We suggest that our proposed method can give precious information on efficient search for the distinguishable patterns so as to reduce the burden of examining all observations in the data.

Purpose: The purpose of this study is to assess risk factors associated with TB co-infection in HIV/AIDS patients taking antiretroviral therapy (ART). Methodology: An observational, analytic, case-control and quantitative study was conducted on a randomly selected 367 HIV and AIDS patients of whom 92 of them were TB co-infected. Data collection was done by using self-structured questionnaire. Result: In this study, educational status, waste disposal system, monthly income, contact history with a patient of active tuberculosis or presence of a family member with active tuberculosis, drug adherence, knowledge on tuberculosis prevention and history of exposure to substance were factors independently associated with the occurrence of active tuberculosis among HIV and Aids patients taking ART. Conclusion: The findings highlight the need for on-going educational, informational and other interventions to address the risk factors of tuberculosis in HIV and Aids patients in order to decrease the rate of TB co-infection / Health Studies / M.A. Public Health

Background: Non-disclosure of HIV positive status to a partner threatens to reverse gains made in prevention of mother-to-child transmission (PMTCT) in resource limited settings. Determining the association between non-disclosure and infant HIV acquisition is important to justify focussing on disclosure as a strategy in PMTCT programmes. Objective: To determine the association between non-disclosure of HIV positive status to a partner and mother-to-child transmission (MTCT). Methods: Using a matched case-control design, we compared 34 HIV positive infants to 146 HIV negative infants and evaluated whether the mothers had disclosed their HIV status to their partner. Results: Non-disclosure was more frequent among cases (overall, 16.7%; cases, 52.8%; controls 7.6%), p<0.001 and significantly associated with MTCT (aOR 8.9 (3.0-26.3); p<0.0001), with male partner involvement partially mediating the effect of non-disclosure on MTCT. Conclusions: There is a need for PMTCT programs to focus on strategies to improve male partner involvement and partner disclosure without compromising the woman’s safety. / Health Studies / M. (Public Health)

Le cancer du sein (CS) est la deuxième cause de décès liés au cancer parmi les femmes dans la plupart des pays industrialisés. Les personnes qui ont le CS peuvent ne pas hériter des mutations causant le cancer de leurs parents. Ainsi, certaines cellules subissent des mutations qui mènent au cancer. Dans le cas de cancer héréditaire, les cellules tumorales contiennent généralement des mutations qui ne sont pas trouvées ailleurs dans l'organisme, mais peuvent maintenir des mutations qui vont répartir dans toutes les cellules. La genèse du CS est le résultat des mutations de gènes qui assurent la régulation de la prolifération cellulaire et la réparation de l’ADN. Deux gènes semblent particulièrement concernés par les mutations. Les gènes ‘Breast Cancer 1’ (BRCA1) et ‘Breast Cancer 2’ (BRCA2), sont impliqués dans la prédisposition génétique de CS. On estime que 5-10% des cas de cancer du sein sont attribuables à une prédisposition génétique. La plupart de ces cancers sont liés à une anomalie du gène BRCA1 ou BRCA2. Plusieurs études ont été menées chez les femmes atteintes de CS sporadique et quelques études se sont concentrées sur celles qui sont porteuses de mutations de BRCA. Alors, notre recherche a été entreprise afin de vérifier l’hypothèse d’une association entre le CS, le mode vie et les habitudes alimentaires chez les Canadiennes-françaises non porteuses des 6 mutations de BRCA les plus fréquentes parmi cette population. Nous avons mené une étude cas-témoins dans cette population. Quelque 280 femmes atteintes du cancer du sein et non-porteuses de mutations de BRCA, ont été recrutées en tant que cas. Les témoins étaient recrutés parmi les membres de la famille des cas (n=15) ou à partir d'autres familles atteintes de CS (n=265). Les participantes étaient de tous âges, recrutées à partir d’une étude de cohorte qui est actuellement en cours, menée par une équipe de chercheurs au Centre Hospitalier Universitaire de Montréal (CHUM) Hôtel-Dieu à Montréal. Les apports alimentaires ont été recueillis par un questionnaire de fréquence semi-quantitatif validé et administré par une nutritionniste, qui portait sur la période avant les deux ans précédant le premier diagnostic de CS pour les cas et la période avant les deux ans précédant l’entrevue téléphonique pour les témoins. Un questionnaire de base était administré par l’infirmière de recherche aux participantes afin de colliger des renseignements sociodémographiques et sur les facteurs de risque du CS. Une association positive et significative a été détectée entre l’âge (plus de 50 ans) auquel les sujets avaient atteint leur Indice de Masse Corporel (IMC) le plus élevé et le CS rapport de cotes (OR) =2,83; intervalle de confiance à 95% (IC95%) (2,34-2,91). De plus, une association positive a été détectée entre un gain de poids de >34 lbs comparativement à un gain de poids de ≤15 lbs, dès l’âge de 20 ans OR=1,68; IC95% (1,10-2,58). Un gain de poids de >24 lbs comparativement à un gain de poids de ≤9 lbs, dès l’âge de 30 ans a aussi montré une augmentation de risque de CS OR=1,96; IC95% (1,46-3,06). Une association positive a aussi été détecté entre, un gain de poids de >12 lbs comparativement à un gain de poids de ≤1 lb, dès l’âge de 40 ans OR=1,91; IC95% (1,53-2,66). Concernant le tabagisme, nous avons observé une association positive et significative reliée à la consommation de plus de 9 paquets-années OR = 1,59; IC95% (1,57-2,87). Il fut suggéré que l’activité physique modéré confère une protection contre le CS: une pratique de > 24,8 (‘metabolic equivalent’) MET-hrs par semaine par rapport à ≤10,7 MET-hrs par semaine, diminue le risque du CS de 52% OR = 0,48 ; IC95% (0,31-0,74). L’activité physique totale (entre 16,2 et 33,2 MET-hrs par semaine), a aussi montré une réduction de risque de CS de 43% OR = 0,57 ; IC95% (0,37-0,87). Toutefois, il n'y avait aucune association entre une activité physique vigoureuse et le risque de CS. L’analyse portant sur les macro- et micro-nutriments et les groupes alimentaires a montré qu’un apport en énergie totale de plus de 2057 Kcal par jour augmentait le risque de CS de 2,5 fois OR = 2,54; IC95% (1,67-3,84). En ce qui concerne la consommation de café, les participantes qui buvaient plus de 8 tasses de café par jour avaient un risque de CS augmenté de 40% OR = 1,40; IC95% (1,09-2,24). Les sujets ayant une consommation dépassant 9 g d’alcool (éthanol) par jour avaient également un risque élevé de 55% OR = 1,55; IC95% (1,02-2,37). De plus, une association positive et significative a été détectée entre le CS et la consommation de plus de deux bouteilles de bière par semaine OR = 1,34; IC95% (1,28-2,11), 10 onces de vin par semaine OR = 1,16; IC95% (1,08-2,58) ou 6 onces de spiritueux par semaine OR = 1,09; IC95% (1,02-2,08), respectivement. En résumé, les résultats de cette recherche supportent l’hypothèse selon laquelle le mode de vie et les habitudes alimentaires jouent un rôle important dans l’étiologie de CS chez les Canadiennes-françaises non porteuses de mutations de BRCA. Les résultats nous permettent de constater que le gain de poids et le tabagisme sont liés à des risques élevés de CS, tandis que l'activité physique modérée aide à réduire ce risque. De plus, nos résultats suggèrent qu’un apport énergétique total relativement élevé et une consommation élevée de café et d'alcool peuvent accroître le risque de ce cancer. Ce travail a permis de mettre l’accent sur une nouvelle direction de recherche, jusqu'à présent non investiguée. Les résultats de ce travail de recherche pourraient contribuer à recueillir de nouvelles informations et des conseils pouvant influencer et aider la population à modifier son mode de vie et ses habitudes alimentaires afin de diminuer le risque de cancer du sein. / Breast cancer (BC) is the second leading cause of cancer-related deaths among women in most industrialised countries. Individuals who have breast cancer may not inherit cancer-causing mutations from their parents. Instead, certain cells undergo mutations that lead to cancer. In the case of hereditary cancer, tumor cells usually contain mutations not found elsewhere in the body, but also harbor a critical mutation shared by all cells. Autosomal dominant alterations in 2 genes, ‘Breast cancer 1’ (BRCA1) and ‘Breast cancer 2’ (BRCA2), are likely to account for familial cases of early-onset BC. It is estimated that 5-10% of breast cancers are due to a genetic predisposition. Most of these cancers are linked to an abnormality in the gene BRCA1 or BRCA2. Several studies have been conducted in women with sporadic BC but few studies have focused on those who carry BRCA mutations. Our research was undertaken to test the hypothesis of an association between the BC, lifestyle and eating habits among French-Canadian women who were non carriers of 6 frequently-occurring BRCA mutations. We conducted a case-control study in a French-Canadian population. Some 280 women with breast cancer and who were non-gene carriers of mutated BRCA gene were recruited as cases. Control subjects were women from families with breast cancer (n=265), except for 15 (5.4%) who came from the same families as cases. Participants of all ages were recruited from an on-going cohort studied by researchers at Centre Hospitalier Universitaire de Montreal (CHUM) Hôtel-Dieu in Montreal. A validated semi-quantitative food frequency questionnaire was administered by a nutritionist on telephone to ascertain dietary intake covering the period prior to 2 years before the initial diagnosis of BC among cases and the period prior to 2 years before the telephone interview for the controls. A core questionnaire was administered by the research team’s nurse to gather information on socio-demographic and lifestyle risk factors. BC risk was increased among subjects who reached their maximum body mass index (BMI) at an older age (more than 50 years) (OR=2.83; 95% CI: 2.34-2.91). In addition, a direct and significant association was noted between weight gain of >34 lbs compared to weight gain of ≤15 lbs, since age 20 (OR=1.68; 95% CI: 1.10-2.58). Moreover, a weight gain of >24 lbs compared to ≤9 lbs, showed an increased risk of BC since age 30 (OR=1.96; 95% CI: 1.46-3.06) and an increased BC risk was also observed with a weight gain of >12 lbs compared to ≤1 lb, since age 40 (OR=1.91; 95% CI: 1.53-2.66). Women who smoked more than 9 pack-years of cigarettes had a higher risk (59%) of BC (OR=1.59; 95% CI: 1.57-2.87). Subjects who engaged in >24.8 metabolic equivalent (MET)-hours per week compared to ≤10.7 MET-hours per week, of moderate physical activity had a 52% decreased risk of BC (OR=0.48; 95% CI: 0.31-0.74). Moreover, total physical activity between 16.2 and 33.2 MET-hours per week showed a 43% lower risk of BC (OR=0.57 95% CI: 0.37-0.87). However, there was no association between vigorous physical activity and BC risk. Energy intakes greater than 2,057 Kcal per day were significantly and positively related to BC risk (OR=2.54; 95%CI: 1.67-3.84). Women who consumed more than 8 cups of coffee per day had a 40% increased risk of BC: OR=1.40 (95%CI: 1.09-2.24). Subjects who consumed more than 9 g of alcohol (ethanol) per day had a heightened risk (55%) of BC: OR=1.55 (95%CI: 1.02-2.37). In addition, a positive and significant association was noted between the consumption of beer, wine and spirits and BC risk. The ORs were 1.34 (95%CI: 1.28-2.11) for >2 bottles of beer per week, OR=1.16 (95%CI: 1.08-2.58) for >10 oz of wine per week and OR=1.09 (95%CI: 1.02-2.08) for >6 oz of spirits per week, respectively. In summary, we found that weight history did affect breast cancer risk. Moreover, smoking appeared to raise the risk, whereas moderate physical activity had a protective effect. Our findings also indicate that relatively high total energy intake and high coffee and alcohol consumption may increase the risk of breast cancer. This work has highlighted an as-yet-untested research focus addressing relationships between lifestyle and dietary habits and BC among non-carriers of BRCA mutations. The report provides advice and guidance on what can be done to influence and change the lifestyle choices as well as dietary habits to help people to reduce their risk of breast cancer.

La prééclampsie est responsable du quart des mortalités maternelles et est la deuxième cause de décès maternels associés à la grossesse au Canada et dans le monde. L’identification d’une stratégie efficace pour la prévention de la prééclampsie est une priorité et un défi primordial dans les milieux de recherche en obstétrique. Le rôle des éléments nutritifs dans le développement de la prééclampsie a récemment reçu davantage d’attention. Plusieurs études cliniques et épidémiologiques ont été menées pour déterminer les facteurs de risque alimentaires potentiels et examiner les effets d’une supplémentation nutritive dans le développement de troubles hypertensifs de la grossesse. Pour déterminer les effets de suppléments antioxydants pris pendant la grossesse sur le risque d’hypertension gestationnelle (HG) et de prééclampsie, un essai multicentrique contrôlé à double insu a été mené au Canada et au Mexique (An International Trial of Antioxidants in the Prevention of Preeclampsia – INTAPP). Les femmes, stratifiées par risque, étaient assignées au traitement expérimental quotidien (1 gramme de vitamine C et 400 UI de vitamine E) ou au placebo. En raison des effets secondaires potentiels, le recrutement pour l’essai a été arrêté avant que l’échantillon complet ait été constitué. Au total, 2640 femmes éligibles ont accepté d’être recrutées, dont 2363 (89.5%) furent incluses dans les analyses finales. Nous n’avons retrouvé aucune évidence qu’une supplémentation prénatale de vitamines C et E réduisait le risque d’HG et de ses effets secondaires (RR 0,99; IC 95% 0,78-1,26), HG (RR 1,04; IC 95% 0,89-1,22) et prééclampsie (RR 1,04; IC 95% 0,75-1,44). Toutefois, une analyse secondaire a révélé que les vitamines C et E augmentaient le risque de « perte fœtale ou de décès périnatal » (une mesure non spécifiée au préalable) ainsi qu’une rupture prématurée des membranes avant terme. Nous avons mené une étude de cohorte prospective chez les femmes enceintes recrutées dans l’INTAPP afin d’évaluer les relations entre le régime alimentaire maternel en début et fin de grossesse et le risque de prééclampsie et d’HG. Un questionnaire de fréquence alimentaire validé était administré deux fois pendant la grossesse (12-18 semaines, 32-34 semaines). Les analyses furent faites séparément pour les 1537 Canadiennes et les 799 Mexicaines en raison de l’hétérogénéité des régimes alimentaires des deux pays. Parmi les canadiennes, après ajustement pour l’indice de masse corporelle (IMC) précédant la grossesse, le groupe de traitement, le niveau de risque (élevé versus faible) et les autres facteurs de base, nous avons constaté une association significative entre un faible apport alimentaire (quartile inférieur) de potassium (OR 1,79; IC 95% 1,03-3,11) et de zinc (OR 1,90; IC 95% 1,07-3,39) et un risque augmenté de prééclampsie. Toujours chez les Canadiennes, le quartile inférieur de consommation d’acides gras polyinsaturés était associé à un risque augmenté d’HG (OR 1,49; IC 95% 1,09-2,02). Aucun des nutriments analysés n’affectait les risques d’HG ou de prééclampsie chez les Mexicaines. Nous avons entrepris une étude cas-témoins à l’intérieur de la cohorte de l’INTAPP pour établir le lien entre la concentration sérique de vitamines antioxydantes et le risque de prééclampsie. Un total de 115 cas de prééclampsie et 229 témoins ont été inclus. Les concentrations de vitamine E ont été mesurées de façon longitudinale à 12-18 semaines (avant la prise de suppléments), à 24-26 semaines et à 32-34 semaines de grossesse en utilisant la chromatographie liquide de haute performance. Lorsqu’examinée en tant que variable continue et après ajustement multivarié, une concentration de base élevée de gamma-tocophérol était associée à un risque augmenté de prééclampsie (quartile supérieur vs quartile inférieur à 24-26 semaines : OR 2,99, IC 95% 1,13-7,89; à 32-34 semaines : OR 4,37, IC 95% 1,35-14,15). Nous n’avons pas trouvé de lien entre les concentrations de alpha-tocophérol et le risque de prééclampsie. En résumé, nous n’avons pas trouvé d’effets de la supplémentation en vitamines C et E sur le risque de prééclampsie dans l’INTAPP. Nous avons toutefois trouvé, dans la cohorte canadienne, qu’une faible prise de potassium et de zinc, tel qu’estimée par les questionnaires de fréquence alimentaire, était associée à un risque augmenté de prééclampsie. Aussi, une plus grande concentration sérique de gamma-tocophérol pendant la grossesse était associée à un risque augmenté de prééclampsie. / Preeclampsia (PE) accounts for about one-quarter of cases of maternal mortality, and ranks second among the causes of pregnancy-associated maternal deaths in Canada and worldwide. The identification of an effective strategy to prevent PE is a priority and fundamental challenge in obstetrics research. The role of nutritional factors in the etiology of PE has recently received increased attention. Many clinical and epidemiological studies have been conducted to investigate potential dietary risk factors for PE and to examine the effects of nutritional supplementation on the development of hypertensive disorders of pregnancy. To investigate the effects of prenatal antioxidant supplementation on the risk of gestational hypertension (GH) and PE, a double blind, multicenter trial (The International Trial of Antioxidants for the Prevention of Preeclampsia – the INTAPP trial) was conducted in Canada and in Mexico. Women were stratified by their risk status and assigned to daily experimental treatment (1 gram vitamin C and 400 IU vitamin E) or to placebo. Due to concerns about potential adverse effects, recruitment for the trial was stopped before the full sample had been achieved. A total of 2640 consenting eligible women had been recruited at that point with 2363 women (89.5%) included in the final analysis. We found no evidence that prenatal supplementation of vitamins C and E reduced the risk of GH and its adverse conditions (RR: 0.99, 95% CI 0.78-1.26), GH (RR 1.04, 95% CI 0.89-1.22), and PE (RR 1.04, 95% CI 0.75-1.44). However, in a secondary analysis, we found that vitamins C and E increased the risk of ‘fetal loss or perinatal death’ (a non-pre-specified outcome) as well as preterm premature rupture of membranes (PPROM). We conducted a prospective cohort study on pregnant women enrolled in the INTAPP trial to investigate the associations between maternal diet in early and late pregnancy and the risk of PE and GH. A validated food frequency questionnaire (FFQ) was administered twice during pregnancy (12-18 weeks, 32-34 weeks). Analyses were conducted separately for 1537 Canadian and 799 Mexican women as there were significant heterogeneities in various nutrient intakes between the two countries. Among Canadian women, after adjusting for pre-pregnancy body mass index (BMI), treatment group, risk stratum (high versus low) and other baseline risk factors, we found that the lowest quartiles of potassium (OR 1.79, 95% CI 1.03-3.11) and zinc (OR 1.90, 95% CI 1.07-3.39) intake were significantly associated with an increased risk of PE. Also in Canadian women, the lowest quartile of polyunsaturated fatty acids was associated with an increased risk of GH (OR 1.49, 95% CI 1.09-2.02). None of the nutrients analyzed were found to be associated with PE and GH risk among Mexican women. We further conducted a case control study ancillary to the INTAPP trial to assess the relationship between plasma concentration of antioxidant vitamins and the risk of PE. A total of 115 PE cases and 229 matched controls were included. Vitamin E concentrations were measured longitudinally at 12-18 weeks (prior to supplementation), 24-26 weeks, and 32-34 weeks of gestation using high-performance liquid chromatography (HPLC). When examined as a continuous variable, and after multivariate adjustment, elevated baseline gamma-tocopherol concentrations were associated with an increased risk of PE (OR 1.35, 95% CI 1.02-1.78). Analyses of repeated measurements indicated that elevated gamma-tocopherol levels were associated with an increased risk of PE (highest vs. lowest quartile at 24-26 weeks: OR 2.99, 95% CI 1.13-7.89; at 32-34 weeks: OR 4.37, 95% CI 1.35-14.15). We found no associations between alpha-tocopherol concentrations and the risk of PE. In summary, we found no effects of vitamins C and E supplementation on the risk of PE in the INTAPP trial. However, in the Canadian cohort we found that lower intakes of potassium and zinc as estimated by the FFQ were associated with an increased risk of PE. Moreover, higher plasma concentration of gamma-tocopherol during pregnancy was associated with an increased risk of PE.