50 research outputs found

    Adult weight change and premenopausal breast cancer risk: A prospective pooled analysis of data from 628,463 women.

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    Early-adulthood body size is strongly inversely associated with risk of premenopausal breast cancer. It is unclear whether subsequent changes in weight affect risk. We pooled individual-level data from 17 prospective studies to investigate the association of weight change with premenopausal breast cancer risk, considering strata of initial weight, timing of weight change, other breast cancer risk factors and breast cancer subtype. Hazard ratios (HR) and 95% confidence intervals (CI) were obtained using Cox regression. Among 628,463 women, 10,886 were diagnosed with breast cancer before menopause. Models adjusted for initial weight at ages 18-24 years and other breast cancer risk factors showed that weight gain from ages 18-24 to 35-44 or to 45-54 years was inversely associated with breast cancer overall (e.g., HR per 5 kg to ages 45-54: 0.96, 95% CI: 0.95-0.98) and with oestrogen-receptor(ER)-positive breast cancer (HR per 5 kg to ages 45-54: 0.96, 95% CI: 0.94-0.98). Weight gain from ages 25-34 was inversely associated with ER-positive breast cancer only and weight gain from ages 35-44 was not associated with risk. None of these weight gains were associated with ER-negative breast cancer. Weight loss was not consistently associated with overall or ER-specific risk after adjusting for initial weight. Weight increase from early-adulthood to ages 45-54 years is associated with a reduced premenopausal breast cancer risk independently of early-adulthood weight. Biological explanations are needed to account for these two separate factors

    JMIR Res Protoc

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    Background: Breast cancer is the most frequent cancer in women in industrialized countries. Lifestyle and environmental factors, particularly endocrine-disrupting pollutants, have been suggested to play a role in breast cancer risk. Current epidemiological studies, although not fully consistent, suggest a positive association of breast cancer risk with exposure to several International Agency for Research on Cancer Group 1 air-pollutant carcinogens, such as particulate matter, polychlorinated biphenyls (PCB), dioxins, Benzo[a]pyrene (BaP), and cadmium. However, epidemiological studies remain scarce and inconsistent. It has been proposed that the menopausal status could modify the relationship between pollutants and breast cancer and that the association varies with hormone receptor status. Objective: The XENAIR project will investigate the association of breast cancer risk (overall and by hormone receptor status) with chronic exposure to selected air pollutants, including particulate matter, nitrogen dioxide (NO2), ozone (O3), BaP, dioxins, PCB-153, and cadmium. Methods: Our research is based on a case-control study nested within the French national E3N cohort of 5222 invasive breast cancer cases identified during follow-up from 1990 to 2011, and 5222 matched controls. A questionnaire was sent to all participants to collect their lifetime residential addresses and information on indoor pollution. We will assess these exposures using complementary models of land-use regression, atmospheric dispersion, and regional chemistry-transport (CHIMERE) models, via a Geographic Information System. Associations with breast cancer risk will be modeled using conditional logistic regression models. We will also study the impact of exposure on DNA methylation and interactions with genetic polymorphisms. Appropriate statistical methods, including Bayesian modeling, principal component analysis, and cluster analysis, will be used to assess the impact of multipollutant exposure. The fraction of breast cancer cases attributable to air pollution will be estimated. Results: The XENAIR project will contribute to current knowledge on the health effects of air pollution and identify and understand environmental modifiable risk factors related to breast cancer risk. Conclusions: The results will provide relevant evidence to governments and policy-makers to improve effective public health prevention strategies on air pollution. The XENAIR dataset can be used in future efforts to study the effects of exposure to air pollution associated with other chronic conditions

    Sources of Pre-Analytical Variations in Yield of DNA Extracted from Blood Samples: Analysis of 50,000 DNA Samples in EPIC

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    The European Prospective Investigation into Cancer and nutrition (EPIC) is a long-term, multi-centric prospective study in Europe investigating the relationships between cancer and nutrition. This study has served as a basis for a number of Genome-Wide Association Studies (GWAS) and other types of genetic analyses. Over a period of 5 years, 52,256 EPIC DNA samples have been extracted using an automated DNA extraction platform. Here we have evaluated the pre-analytical factors affecting DNA yield, including anthropometric, epidemiological and technical factors such as center of subject recruitment, age, gender, body-mass index, disease case or control status, tobacco consumption, number of aliquots of buffy coat used for DNA extraction, extraction machine or procedure, DNA quantification method, degree of haemolysis and variations in the timing of sample processing. We show that the largest significant variations in DNA yield were observed with degree of haemolysis and with center of subject recruitment. Age, gender, body-mass index, cancer case or control status and tobacco consumption also significantly impacted DNA yield. Feedback from laboratories which have analyzed DNA with different SNP genotyping technologies demonstrate that the vast majority of samples (approximately 88%) performed adequately in different types of assays. To our knowledge this study is the largest to date to evaluate the sources of pre-analytical variations in DNA extracted from peripheral leucocytes. The results provide a strong evidence-based rationale for standardized recommendations on blood collection and processing protocols for large-scale genetic studies

    Sources of Pre-Analytical Variations in Yield of DNA Extracted from Blood Samples: Analysis of 50,000 DNA Samples in EPIC

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    The European Prospective Investigation into Cancer and nutrition (EPIC) is a long-term, multi-centric prospective study in Europe investigating the relationships between cancer and nutrition. This study has served as a basis for a number of Genome-Wide Association Studies (GWAS) and other types of genetic analyses. Over a period of 5 years, 52,256 EPIC DNA samples have been extracted using an automated DNA extraction platform. Here we have evaluated the pre-analytical factors affecting DNA yield, including anthropometric, epidemiological and technical factors such as center of subject recruitment, age, gender, body-mass index, disease case or control status, tobacco consumption, number of aliquots of buffy coat used for DNA extraction, extraction machine or procedure, DNA quantification method, degree of haemolysis and variations in the timing of sample processing. We show that the largest significant variations in DNA yield were observed with degree of haemolysis and with center of subject recruitment. Age, gender, body-mass index, cancer case or control status and tobacco consumption also significantly impacted DNA yield. Feedback from laboratories which have analyzed DNA with different SNP genotyping technologies demonstrate that the vast majority of samples (approximately 88%) performed adequately in different types of assays. To our knowledge this study is the largest to date to evaluate the sources of pre-analytical variations in DNA extracted from peripheral leucocytes. The results provide a strong evidence-based rationale for standardized recommendations on blood collection and processing protocols for large-scale genetic studies

    Breast Cancer Risk After Recent Childbirth: A Pooled Analysis of 15 Prospective Studies.

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    Background Parity is widely recognized as protective for breast cancer, but breast cancer risk may be increased shortly after childbirth. Whether this risk varies with breastfeeding, family history of breast cancer, or specific tumor subtype has rarely been evaluated.Objective To characterize breast cancer risk in relation to recent childbirth.Design Pooled analysis of individual-level data from 15 prospective cohort studies.Setting The international Premenopausal Breast Cancer Collaborative Group.Participants Women younger than 55 years.Measurements During 9.6 million person-years of follow-up, 18 826 incident cases of breast cancer were diagnosed. Hazard ratios (HRs) and 95% CIs for breast cancer were calculated using Cox proportional hazards regression.Results Compared with nulliparous women, parous women had an HR for breast cancer that peaked about 5 years after birth (HR, 1.80 [95% CI, 1.63 to 1.99]) before decreasing to 0.77 (CI, 0.67 to 0.88) after 34 years. The association crossed over from positive to negative about 24 years after birth. The overall pattern was driven by estrogen receptor (ER)-positive breast cancer; no crossover was seen for ER-negative cancer. Increases in breast cancer risk after childbirth were pronounced when combined with a family history of breast cancer and were greater for women who were older at first birth or who had more births. Breastfeeding did not modify overall risk patterns.Limitations Breast cancer diagnoses during pregnancy were not uniformly distinguishable from early postpartum diagnoses. Data on human epidermal growth factor receptor 2 (HER2) oncogene overexpression were limited.Conclusion Compared with nulliparous women, parous women have an increased risk for breast cancer for more than 20 years after childbirth. Health care providers should consider recent childbirth a risk factor for breast cancer in young women.Primary funding source The Avon Foundation, the National Institute of Environmental Health Sciences, Breast Cancer Now and the UK National Health Service, and the Institute of Cancer Research

    Association of Body Mass Index and Age With Subsequent Breast Cancer Risk in Premenopausal Women.

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    Importance: The association between increasing body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) and risk of breast cancer is unique in cancer epidemiology in that a crossover effect exists, with risk reduction before and risk increase after menopause. The inverse association with premenopausal breast cancer risk is poorly characterized but might be important in the understanding of breast cancer causation. Objective: To investigate the association of BMI with premenopausal breast cancer risk, in particular by age at BMI, attained age, risk factors for breast cancer, and tumor characteristics. Design, Setting, and Participants: This multicenter analysis used pooled individual-level data from 758 592 premenopausal women from 19 prospective cohorts to estimate hazard ratios (HRs) of premenopausal breast cancer in association with BMI from ages 18 through 54 years using Cox proportional hazards regression analysis. Median follow-up was 9.3 years (interquartile range, 4.9-13.5 years) per participant, with 13 082 incident cases of breast cancer. Participants were recruited from January 1, 1963, through December 31, 2013, and data were analyzed from September 1, 2013, through December 31, 2017. Exposures: Body mass index at ages 18 to 24, 25 to 34, 35 to 44, and 45 to 54 years. Main Outcomes and Measures: Invasive or in situ premenopausal breast cancer. Results: Among the 758 592 premenopausal women (median age, 40.6 years; interquartile range, 35.2-45.5 years) included in the analysis, inverse linear associations of BMI with breast cancer risk were found that were stronger for BMI at ages 18 to 24 years (HR per 5 kg/m2 [5.0-U] difference, 0.77; 95% CI, 0.73-0.80) than for BMI at ages 45 to 54 years (HR per 5.0-U difference, 0.88; 95% CI, 0.86-0.91). The inverse associations were observed even among nonoverweight women. There was a 4.2-fold risk gradient between the highest and lowest BMI categories (BMI≥35.0 vs <17.0) at ages 18 to 24 years (HR, 0.24; 95% CI, 0.14-0.40). Hazard ratios did not appreciably vary by attained age or between strata of other breast cancer risk factors. Associations were stronger for estrogen receptor-positive and/or progesterone receptor-positive than for hormone receptor-negative breast cancer for BMI at every age group (eg, for BMI at age 18 to 24 years: HR per 5.0-U difference for estrogen receptor-positive and progesterone receptor-positive tumors, 0.76 [95% CI, 0.70-0.81] vs hormone receptor-negative tumors, 0.85 [95% CI: 0.76-0.95]); BMI at ages 25 to 54 years was not consistently associated with triple-negative or hormone receptor-negative breast cancer overall. Conclusions and Relevance: The results of this study suggest that increased adiposity is associated with a reduced risk of premenopausal breast cancer at a greater magnitude than previously shown and across the entire distribution of BMI. The strongest associations of risk were observed for BMI in early adulthood. Understanding the biological mechanisms underlying these associations could have important preventive potential

    Modeling the spread of avian influenza viruses in aquatic reservoirs : a novel hydrodynamic approach applied to the Rhone delta (southern France)

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    Wild aquatic birds represent a natural reservoir of avian influenza viruses (AIV) that can be spread to poultry. AIV epizootics were associated with huge economic impacts during the last decades and are still of major concern. Within aquatic bird populations AIV are transmitted either by direct contact or through the ingestion of water that has been contaminated by infected individuals. This second route involving environmental transmission is of utmost importance in AIV dynamics, yet it has received far less attention than direct bird-to-bird contamination. Our objective was to combine a hydrodynamic model with data on mallard abundance and AIV infection rate within the population, so as to characterize virus dissemination within a complex wetland network. We chose the VaccarSs hydrosystem as a wetland model since it represents a large part of the Camargue region, which is a major wintering site for a large diversity of aquatic birds including AIV hosts. We aimed to identify the environmental parameters that drive AIV dynamics within this system and the spatio-temporal pattern of dispersion and persistence of viruses. Our results show that in a complex hydrosystemwe can expect a great heterogeneity in AIV risk among wetlands. Our simulations underline how a simple " homogeneous box" approach could in the case of deltaic ecosystemsminimize the expected risk by diluting it in the whole system. Moreover, such undermining of the risk perception could affect the predictions relative to risk duration. We present a new approach to identify hotspots of virus concentrations within deltaic areas that could take advantage of the duck count data, AIV surveys and hydrodynamicmodels thatmay already be available in severalmajor duck wintering areas comprised of complex hydrosystems, such as the large European deltas. Our method could be of particular interest to optimize surveillance strategies in the current context of highly pathogenic AIV diffusion within wild bird populations

    An Unstructured Numerical Model to Study Wind-Driven Circulation Patterns in a Managed Coastal Mediterranean Wetland: The Vaccares Lagoon System

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    The spatiotemporal structure of wind-driven circulation patterns and associated water exchanges can drive important bio-hydrodynamic interactions in shallow lagoons. The Vaccares lagoon system is a complex shallow hydrosystem located in the central part of the Rhone Delta (France). It is internationally recognized as part of a biosphere reserve within the framework of UNESCO's Man and Biosphere Programme, and as a RAMSAR site. Due to its frequent occurrence in this area, and considering the shallowness of the Vaccares lagoon system, wind is assumed to play a major role in the hydrodynamic and biological processes. In this study, a hydrodynamic model was developed to investigate the structure of wind-driven circulations in the Vaccares lagoon system, to provide insights into their role in transport and water exchange processes. The implementation and assessment (calibration and validation) of the model is presented first. Simulations were then performed for two typical steady wind conditions and for one measured unsteady wind event. The results illustrate the influence of the complex geometry of the Vaccares lagoon system on the wind-driven circulations, and the differences observed between the different sub-lagoons in this system. The differences in wind-induced water exchanges between these sub-lagoons are also discussed
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