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Sökning: WFRF:(Spencer Elizabeth A)

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1.
  • Bellenguez, Celine, et al. (författare)
  • Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke
  • 2012
  • Ingår i: Nature Genetics. - Nature Publishing Group. - 1061-4036. ; 44:3, s. 328-U141
  • Tidskriftsartikel (refereegranskat)abstract
    • Genetic factors have been implicated in stroke risk, but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) for ischemic stroke and its subtypes in 3,548 affected individuals and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 affected individuals and 6,281 controls. We replicated previous associations for cardioembolic stroke near PITX2 and ZFHX3 and for large vessel stroke at a 9p21 locus. We identified a new association for large vessel stroke within HDAC9 (encoding histone deacetylase 9) on chromosome 7p21.1 (including further replication in an additional 735 affected individuals and 28,583 controls) (rs11984041; combined P = 1.87 x 10(-11); odds ratio (OR) = 1.42, 95% confidence interval (CI) = 1.28-1.57). All four loci exhibited evidence for heterogeneity of effect across the stroke subtypes, with some and possibly all affecting risk for only one subtype. This suggests distinct genetic architectures for different stroke subtypes.
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2.
  • Beecham, Ashley H., et al. (författare)
  • Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis
  • 2013
  • Ingår i: Nature Genetics. - NATURE PUBLISHING GROUP, 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA. - 1061-4036. ; 45:11, s. 1353-
  • Tidskriftsartikel (refereegranskat)abstract
    • Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P andlt; 1.0 x 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P andlt; 5.0 x 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
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4.
  • Linseisen, Jakob, et al. (författare)
  • Dietary intake of different types and characteristics of processed meat which might be associated with cancer risk--results from the 24-hour diet recalls in the European Prospective Investigation into Cancer and Nutrition (EPIC).
  • 2006
  • Ingår i: Public Health Nutr. - 1368-9800. ; 9:4, s. 449-64
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: There is increasing evidence for a significant effect of processed meat (PM) intake on cancer risk. However, refined knowledge on how components of this heterogeneous food group are associated with cancer risk is still missing. Here, actual data on the intake of PM subcategories is given; within a food-based approach we considered preservation methods, cooking methods and nutrient content for stratification, in order to address most of the aetiologically relevant hypotheses. Design and setting: Standardised computerised 24-hour diet recall interviews were collected within the framework of the European Prospective Investigation into Cancer and Nutrition (EPIC), a prospective cohort study in 27 centres across 10 European countries. Subjects: Subjects were 22 924 women and 13 031 men aged 35 - 74 years. Results: Except for the so-called 'health-conscious' cohort in the UK, energy-adjusted total PM intake ranged between 11.1 and 47.9 g day(-1) in women and 18.8 and 88.5 g day(-1) in men. Ham, salami-type sausages and heated sausages contributed most to the overall PM intake. The intake of cured (addition of nitrate/nitrite) PM was highest in the German, Dutch and northern European EPIC centres, with up to 68.8 g day(-1) in men. The same was true for smoked PM (up to 51.8 g day(-1)). However, due to the different manufacturing practice, the highest average intake of NaNO2 through PM consumption was found for the Spanish centres (5.4 mg day(-1) in men) as compared with German and British centres. Spanish centres also showed the highest intake of NaCl-rich types of PM; most cholesterol- and iron-rich PM was consumed in central and northern European centres. Possibly hazardous cooking methods were more often used for PM preparation in central and northern European centres. Conclusions: We applied a food-based categorisation of PM that addresses aetiologically relevant mechanisms for cancer development and found distinct differences in dietary intake of these categories of PM across European cohorts. This predisposes EPIC to further investigate the role of PM in cancer aetiology.
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5.
  • May, Anne M., et al. (författare)
  • Determinants of non- response to a second assessment of lifestyle factors and body weight in the EPIC-PANACEA study
  • 2012
  • Ingår i: BMC Medical Research Methodology. - BioMed Central. - 1471-2288. ; 12:148
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: This paper discusses whether baseline demographic, socio-economic, health variables, length of follow-up and method of contacting the participants predict non-response to the invitation for a second assessment of lifestyle factors and body weight in the European multi-center EPIC-PANACEA study. Methods: Over 500.000 participants from several centers in ten European countries recruited between 1992 and 2000 were contacted 2-11 years later to update data on lifestyle and body weight. Length of follow-up as well as the method of approaching differed between the collaborating study centers. Non-responders were compared with responders using multivariate logistic regression analyses. Results: Overall response for the second assessment was high (81.6%). Compared to postal surveys, centers where the participants completed the questionnaire by phone attained a higher response. Response was also high in centers with a short follow-up period. Non-response was higher in participants who were male (odds ratio 1.09 (confidence interval 1.07; 1.11), aged under 40 years (1.96 (1.90; 2.02), living alone (1.40 (1.37; 1.43), less educated (1.35 (1.12; 1.19), of poorer health (1.33 (1.27; 1.39), reporting an unhealthy lifestyle and who had either a low (<18.5 kg/m2, 1.16 (1.09; 1.23)) or a high BMI (>25, 1.08 (1.06; 1.10); especially >= 30 kg/m2, 1.26 (1.23; 1.29)). Conclusions: Cohort studies may enhance cohort maintenance by paying particular attention to the subgroups that are most unlikely to respond and by an active recruitment strategy using telephone interviews.
6.
  • Orfanos, Philippos, et al. (författare)
  • Eating out of home and its correlates in 10 European countries. The European Prospective Investigation into Cancer and Nutrition (EPIC) study.
  • 2007
  • Ingår i: Public Health Nutrition. - 1368-9800. ; 10:12, s. 1515-1525
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To compare the average out-of-home (OH) consumption of foods and beverages, as well as energy intake, among populations from 10 European countries and to describe the characteristics of substantial OH eaters, as defined for the purpose of the present study, in comparison to other individuals. DESIGN: Cross-sectional study. Dietary data were collected through single 24-hour dietary recalls, in which the place of consumption was recorded. For the present study, substantial OH eaters were defined as those who consumed more than 25% of total daily energy intake at locations other than the household premises. Mean dietary intakes and the proportion of substantial OH eaters are presented by food group and country. Logistic regression analyses were used to estimate the odds of being a substantial OH eater in comparison to not being one, using mutually adjusted possible non-dietary determinants. SETTING: Ten European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). SUBJECTS: The subjects were 34 270 individuals, 12 537 men and 21 733 women, aged 35-74 years. RESULTS: The fraction of energy intake during OH eating was generally higher in northern European countries than in the southern ones. Among the food and beverage groups, those selectively consumed outside the home were coffee/tea/waters and sweets and, to a lesser extent, cereals, meats, added lipids and vegetables. Substantial OH eating was positively associated with energy intake and inversely associated with age and physical activity. Substantial OH eating was less common among the less educated compared with the more educated, and more common during weekdays in central and north Europe and during the weekend in south Europe. CONCLUSIONS: Eating outside the home was associated with sedentary lifestyle and increased energy intake; it was more common among the young and concerned in particular coffee/tea/waters and sweets.
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7.
  • Steffen, Annika, et al. (författare)
  • Anthropometry and esophageal cancer risk in the European prospective investigation into cancer and nutrition
  • 2009
  • Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965. ; 18:7, s. 2079-2089
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Increasing evidence suggests that general obesity [measured by body mass index (BMI)] is positively associated with risk of esophageal adenocarcinoma (EAC). In contrast, previous studies have shown inverse relations with esophageal squamous cell carcinoma (ESCC). However, it is still unclear whether body fat distribution, particularly abdominal obesity, is associated with each type of esophageal cancer. METHODS: We applied multivariable adjusted Cox proportional hazards regression to investigate the association between anthropometric measures and risk of EAC and ESCC among 346,554 men and women participating in the European Prospective Investigation into Cancer and Nutrition. All statistical tests were two sided. RESULTS: During 8.9 years of follow-up, we documented 88 incident cases of EAC and 110 cases of ESCC. BMI, waist circumference, and waist-to-hip ratio (WHR) were positively associated with EAC risk [highest versus lowest quintile; relative risk (RR), 2.60; 95% confidence interval (95% CI), 1.23-5.51; P(trend) < 0.01; RR, 3.07; 95% CI, 1.35-6.98; P(trend) < 0.003; and RR, 2.12; 95% CI, 0.98-4.57; P(trend) < 0.004]. In contrast, BMI and waist circumference were inversely related to ESCC risk, whereas WHR showed no association with ESCC. In stratified analyses, BMI and waist circumference were significantly inversely related to ESCC only among smokers but not among nonsmokers. However, when controlled for BMI, we found positive associations for waist circumference and WHR with ESCC, and these associations were observed among smokers and nonsmokers. CONCLUSION: General and abdominal obesity were associated with higher EAC risk. Further, our study suggests that particularly an abdominal body fat distribution might also be a risk factor for ESCC.
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8.
  • van Boeckel, Petra G A, et al. (författare)
  • No association between educational level and pancreatic cancer incidence in the European Prospective Investigation into Cancer and Nutrition
  • 2010
  • Ingår i: Cancer Epidemiology. - Elsevier Science Ltd. - 1877-7821. ; 34:6, s. 696-701
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Until now, studies examining the relationship between socioeconomic status and pancreatic cancer incidence have been inconclusive. Aim: To prospectively investigate to what extent pancreatic cancer incidence varies according to educational level within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Methods: In the EPIC study, socioeconomic status at baseline was measured using the highest level of education attained. Hazard ratios by educational level and a summary index, the relative indices of inequality (Rh), were estimated using Cox regression models stratified by age, gender, and center and adjusted for known risk factors. In addition, we conducted separate analyses by age, gender and geographical region. Results: Within the source population of 407, 944 individuals at baseline, 490 first incident primary pancreatic adenocarcinoma cases were identified in 9 European countries. The crude difference in risk of pancreatic cancer according to level of education was small and not statistically significant (RII = 1.14, 95% CI 0.80-1.62). Adjustment for known risk factors reduced the inequality estimates to only a small extent. In addition, no statistically significant associations were observed for age groups (adjusted RII <= (60) (years) = 0.85, 95% CI 0.44-1.64, adjusted RII> 60 years = 1.18, 95% CI 0.73-1.90), gender (adjusted RIImale = 1.20, 95% CI 0.68-2.10, adjusted RIIfemale = 0.96, 95% CI 0.56-1.62) or geographical region (adjusted RIINorthern Europe = 1.14, 95% CI 0.81-1.61, adjusted RIIMiddle (Europe) = 1.72, 95% CI 0.93-3.19, adjusted RIISouthern Europe = 0.75, 95% CI 0.32-1.80). Conclusion: Despite large educational inequalities in many risk factors within the EPIC study, we found no evidence for an association between educational level and the risk of developing pancreatic cancer in this European cohort. (C) 2010 Elsevier Ltd. All rights reserved.
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9.
  • Bamia, Christina, et al. (författare)
  • Dietary patterns and survival of older Europeans : the EPIC-Elderly Study (European Prospective Investigation into Cancer and Nutrition).
  • 2007
  • Ingår i: Public Health Nutrition. - 1368-9800. ; 10:6, s. 590-8
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To investigate the association of a posteriori dietary patterns with overall survival of older Europeans. Design and setting: This is a multi-centre cohort study. Cox regression analysis was used to investigate the association of the prevailing, a posteriori-derived, plant-based dietary pattern with all-cause mortality in a population of subjects who were 60 years or older at recruitment to the European Prospective Investigation into Cancer and Nutrition (EPIC-Elderly cohort). Analyses controlled for all known potential risk factors. Subjects: in total, 74 607 men and women, 60 years or older at enrolment and without previous coronary heart disease, stroke or cancer, with complete information about dietary intakes and potentially confounding variables, and with known survival status as of December 2003, were included in the analysis. Results: An increase in the score which measures the adherence to the plant-based diet was associated with a lower overall mortality, a one standard deviation increment corresponding to a statistically significant reduction of 14% (95% confidence interval 5-23%). In country-specific analyses the apparent association was stronger in Greece, Spain, Denmark and The Netherlands, and absent in the UK and Germany. Conclusions: Greater adherence to the plant-based diet that was defined a posteriori in this population of European elders is associated with lower all-cause mortality. This dietary score is moderately positively correlated with the Modified Mediterranean Diet Score that has been constructed a priori and was also shown to be beneficial for the Survival of the same EPIC-Elderly cohort.
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10.
  • Hoeft, Birgit, et al. (författare)
  • Polymorphisms in fatty acid metabolism-related genes are associated with colorectal cancer risk.
  • 2010
  • Ingår i: Carcinogenesis. - 0143-3334. ; 31:3, s. 466-472
  • Tidskriftsartikel (refereegranskat)abstract
    • Colorectal cancer is the third most common malignant tumor and the fourth-leading cause of cancer death worldwide. The crucial role of fatty acids for a number of important biological processes suggests a more in depth analysis of inter-individual differences in fatty acid metabolizing genes as contributing factor to colon carcinogenesis. We examined the association between genetic variability in 43 fatty acid metabolism-related genes and colorectal risk in 1225 CRC cases and 2032 controls participating in the European Prospective Investigation into Cancer and Nutrition study. 392 single nucleotide polymorphisms were selected using pairwise tagging with an r(2) cutoff of 0.8 and a minor allele frequency of >5%. Conditional logistic regression models were used to estimate odds ratios and corresponding 95% confidence intervals. Haplotype analysis was performed using a generalized linear model framework. On the genotype level, HPGD, PLA2G6, and TRPV3 were associated with higher risk for colorectal cancer, while PTGER2 was associated with lower colorectal cancer risk. A significant inverse association (p < 0.006) was found for PTGER2 GGG haplotype while HPGD AGGAG and PLA2G3 CT haplotypes were significantly (p < 0.001 and p = 0.003, respectively) associated with higher risk of colorectal cancer. Based on these data we present for the first time the association of HPGD variants with colorectal cancer risk. Our results support the key role of prostanoid signaling in colon carcinogenesis and suggest a relevance of genetic variation in fatty acid metabolism-related genes and colorectal cancer risk.
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