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1.
  • Emerging Risk Factors, Collaboration, et al. (författare)
  • The Emerging Risk Factors Collaboration: analysis of individual data on lipid, inflammatory and other markers in over 1.1 million participants in 104 prospective studies of cardiovascular diseases
  • 2007
  • Ingår i: Eur J Epidemiol. - 0393-2990. ; 22:12, s. 839-69
  • Tidskriftsartikel (refereegranskat)abstract
    • Many long-term prospective studies have reported on associations of cardiovascular diseases with circulating lipid markers and/or inflammatory markers. Studies have not, however, generally been designed to provide reliable estimates under different circumstances and to correct for within-person variability. The Emerging Risk Factors Collaboration has established a central database on over 1.1 million participants from 104 prospective population-based studies, in which subsets have information on lipid and inflammatory markers, other characteristics, as well as major cardiovascular morbidity and cause-specific mortality. Information on repeat measurements on relevant characteristics has been collected in approximately 340,000 participants to enable estimation of and correction for within-person variability. Re-analysis of individual data will yield up to approximately 69,000 incident fatal or nonfatal first ever major cardiovascular outcomes recorded during about 11.7 million person years at risk. The primary analyses will involve age-specific regression models in people without known baseline cardiovascular disease in relation to fatal or nonfatal first ever coronary heart disease outcomes. This initiative will characterize more precisely and in greater detail than has previously been possible the shape and strength of the age- and sex-specific associations of several lipid and inflammatory markers with incident coronary heart disease outcomes (and, secondarily, with other incident cardiovascular outcomes) under a wide range of circumstances. It will, therefore, help to determine to what extent such associations are independent from possible confounding factors and to what extent such markers (separately and in combination) provide incremental predictive value.
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  • Ballantyne, C., et al. (författare)
  • Collaborative meta-analysis of individual participant data from observational studies of Lp-PLA(2) and cardiovascular diseases
  • 2007
  • Ingår i: European Journal of Cardiovascular Prevention & Rehabilitation. - 1741-8275. ; 14:1, s. 41344-41344
  • Forskningsöversikt (refereegranskat)abstract
    • Background A large number of observational epidemiological studies have reported generally positive associations' between circulating mass and activity levels of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) and the risk of cardiovascular diseases. Few studies have been large enough to provide reliable estimates in different circumstances, such as in different subgroups (e.g., by age group, sex, or smoking status) or at different Lp-PLA2 levels. Moreover, most published studies have related disease risk only to baseline values of Lp-PLA(2) markers (which can lead to substantial underestimation of any risk relationships because of within-person variability over time) and have used different approaches to adjustment for possible confounding factors. Objectives By combination of data from individual participants from all relevant observational studies in a systematic,meta-analysis, with correction for regression dilution (using available data on serial measurements of Lp-PLA(2)), the Lp-PLA(2) Studies Collaboration will aim to characterize more precisely than has previously been possible the strength and shape of the age and sex-specific associations of plasma Lp-PLA(2) with coronary heart disease (and, where data are sufficient with other vascular diseases, such as ischaemic stroke). It will also help to determine to what extent such associations are independent of possible confounding factors and to explore potential sources of heterogeneity among studies, such as those related to assay methods and study design. It is anticipated that the present collaboration will serve as a framework to investigate related questions on Lp-PLA(2) and cardiovascular outcomes. Methods A central database is being established containing data on circulating Lp-PLA(2) values, sex and other potential confounding factors, age at baseline Lp-PLA(2) Measurement, age at event or at last follow-up, major vascular morbidity and cause-specific mortality. Information about any repeat measurements of Lp-PLA2 and potential confounding factors has been sought to allow adjustment for possible confounding and correction for regression dilution. The analyses will involve age-specific regression models. Synthesis of the available observational studies of Lp-PLA(2) will yield information on a total of about 15 000 cardiovascular disease endpoints.
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3.
  • Ballantyne, C., et al. (författare)
  • Collaborative meta-analysis of individual participant data from observational studies of Lp-PLA2 and cardiovascular diseases
  • 2007
  • Ingår i: European Journal of Cardiovascular Prevention & Rehabilitation. - : Oxford University Press (OUP). - 1741-8267 .- 1741-8275 .- 2047-4873. ; 14:1, s. 3-11
  • Forskningsöversikt (refereegranskat)abstract
    • BACKGROUND: A large number of observational epidemiological studies have reported generally positive associations between circulating mass and activity levels of lipoprotein-associated phospholipase A2 (Lp-PLA2) and the risk of cardiovascular diseases. Few studies have been large enough to provide reliable estimates in different circumstances, such as in different subgroups (e.g., by age group, sex, or smoking status) or at different Lp-PLA2 levels. Moreover, most published studies have related disease risk only to baseline values of Lp-PLA2 markers (which can lead to substantial underestimation of any risk relationships because of within-person variability over time) and have used different approaches to adjustment for possible confounding factors. OBJECTIVES: By combination of data from individual participants from all relevant observational studies in a systematic 'meta-analysis', with correction for regression dilution (using available data on serial measurements of Lp-PLA2), the Lp-PLA2 Studies Collaboration will aim to characterize more precisely than has previously been possible the strength and shape of the age and sex-specific associations of plasma Lp-PLA2 with coronary heart disease (and, where data are sufficient, with other vascular diseases, such as ischaemic stroke). It will also help to determine to what extent such associations are independent of possible confounding factors and to explore potential sources of heterogeneity among studies, such as those related to assay methods and study design. It is anticipated that the present collaboration will serve as a framework to investigate related questions on Lp-PLA2 and cardiovascular outcomes. METHODS: A central database is being established containing data on circulating Lp-PLA2 values, sex and other potential confounding factors, age at baseline Lp-PLA2 measurement, age at event or at last follow-up, major vascular morbidity and cause-specific mortality. Information about any repeat measurements of Lp-PLA2 and potential confounding factors has been sought to allow adjustment for possible confounding and correction for regression dilution. The analyses will involve age-specific regression models. Synthesis of the available observational studies of Lp-PLA2 will yield information on a total of about 15 000 cardiovascular disease endpoints.
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  • Lumbreras, B., et al. (författare)
  • Meat intake and bladder cancer in a prospective study: a role for heterocyclic aromatic amines?
  • 2008
  • Ingår i: Cancer Causes and Control. - : Springer Science and Business Media LLC. - 1573-7225 .- 0957-5243. ; 19:6, s. 649-656
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective The suspect carcinogens, heterocyclic amines (HAAs), found in well-done meat require host-mediated metabolic activation before inducing DNA mutations. The role of SULT1A1 and of NAT2 on the activation of HAAs suggests that NAT2 rapid acetylator genotype and SULT1A1 allele variants can have an effect on HAA carcinogenicity. Methods Data were collected as part of a case-control study nested within the EPIC cohort, the Gen Air investigation. EPIC is a prospective study designed to investigate the relationship between nutrition and cancer. Information was collected through a non-dietary questionnaire on lifestyle variables and through a dietary questionnaire. The subjects were restricted to non-smokers. We calculated the matched odds ratio for bladder cancer risk using logistic regression, controlling for potential confounders. Results There were 227 bladder cases and 612 controls matched 1:3. Meat intake and NAT2 genotype were not independently associated with bladder cancer risk. A significant relationship was observed between bladder cancer risk and consumption of meat only among subjects with the rapid NAT2 genotype (odds ratios [OR] 2.9, 95% CI 1.0-7.9 for the 2nd quartile of meat intake; 3.6, 95% CI 1.3-9.7 for the 3rd quartile; and 3.5, 95% CI 1.2-9.7 for the 4th quartile), and was not present among subjects with the slow genotype. An interaction between NAT2 and meat intake was found in logistic regression (P = 0.034). No association was observed for SULT1A *1/2 genotype (1.0; 95% CI 0.7-1.5) and for SULT1A1 *2/2 genotype (0.9; 95% CI 0.5-1.7). Conclusions These results are suggestive of a role of meat intake and NAT2 on bladder cancer risk. They support the hypothesis that among subjects with the rapid NAT2 acetylation genotype higher levels of HAAs exposure are a bladder cancer risk factor. We did not observe an effect of SULT1A1 allele variants on this cancer. The present study adds new information on the possible long-term adverse effects of diets with high meat intake.
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6.
  • Orfanos, P, 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. - 1475-2727 .- 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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  • Allen, N. E., et al. (författare)
  • Animal foods, protein, calcium and prostate cancer risk: the European Prospective Investigation into Cancer and Nutrition
  • 2008
  • Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 98:9, s. 1574-1581
  • Tidskriftsartikel (refereegranskat)abstract
    • We examined consumption of animal foods, protein and calcium in relation to risk of prostate cancer among 142 251 men in the European Prospective Investigation into Cancer and Nutrition. Associations were examined using Cox regression, stratified by recruitment centre and adjusted for height, weight, education, marital status and energy intake. After an average of 8.7 years of follow-up, there were 2727 incident cases of prostate cancer, of which 1131 were known to be localised and 541 advanced-stage disease. A high intake of dairy protein was associated with an increased risk, with a hazard ratio for the top versus the bottom fifth of intake of 1.22 (95% confidence interval (CI): 1.07-1.41, P-trend = 0.02). After calibration to allow for measurement error, we estimated that a 35-g day(-1) increase in consumption of dairy protein was associated with an increase in the risk of prostate cancer of 32% (95% CI: 1-72%, P-trend = 0.04). Calcium from dairy products was also positively associated with risk, but not calcium from other foods. The results support the hypothesis that a high intake of protein or calcium from dairy products may increase the risk for prostate cancer.
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  • Manuguerra, M., et al. (författare)
  • Multi-factor dimensionality reduction applied to a large prospective investigation on gene-gene and gene-environment interactions
  • 2007
  • Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 28:2, s. 414-422
  • Tidskriftsartikel (refereegranskat)abstract
    • It is becoming increasingly evident that single-locus effects cannot explain complex multifactorial human diseases like cancer. We applied the multi-factor dimensionality reduction (MDR) method to a large cohort study on gene-environment and gene-gene interactions. The study (case-control nested in the EPIC cohort) was established to investigate molecular changes and genetic susceptibility in relation to air pollution and environmental tobacco smoke (ETS) in non-smokers. We have analyzed 757 controls and 409 cases with bladder cancer (n = 124), lung cancer (n = 116) and myeloid leukemia (n = 169). Thirty-six gene variants (DNA repair and metabolic genes) and three environmental exposure variables (measures of air pollution and ETS at home and at work) were analyzed. Interactions were assessed by prediction error percentage and cross-validation consistency (CVC) frequency. For lung cancer, the best model was given by a significant gene-environment association between the base excision repair (BER) XRCC1-Arg399Gln polymorphism, the double-strand break repair (DSBR) BRCA2-Asn372His polymorphism and the exposure variable 'distance from heavy traffic road', an indirect and robust indicator of air pollution (mean prediction error of 26%, P < 0.001, mean CVC of 6.60, P = 0.02). For bladder cancer, we found a significant 4-loci association between the BER APE1-Asp148Glu polymorphism, the DSBR RAD52-3'-untranslated region (3'-UTR) polymorphism and the metabolic gene polymorphisms COMT-Val158Met and MTHFR-677C > T (mean prediction error of 22%, P < 0.001, mean CVC consistency of 7.40, P < 0.037). For leukemia, a 3-loci model including RAD52-2259C > T, MnSOD-Ala9Val and CYP1A1-Ile462Val had a minimum prediction error of 31% (P < 0.001) and a maximum CVC of 4.40 (P = 0.086). The MDR method seems promising, because it provides a limited number of statistically stable interactions; however, the biological interpretation remains to be understood.
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  • van Gils, C H, et al. (författare)
  • Consumption of vegetables and fruits and risk of breast cancer
  • 2005
  • Ingår i: JAMA: The Journal of the American Medical Association. - 1538-3598. ; 293:2, s. 183-193
  • Tidskriftsartikel (refereegranskat)abstract
    • Context The intake of vegetables and fruits has been thought to protect against breast cancer. Most of the evidence comes from case-control studies, but a recent pooled analysis of the relatively few published cohort studies suggests no significantly reduced breast cancer risk is associated with vegetable and fruit consumption. Objective To examine the relation between total and specific vegetable and fruit intake and the incidence of breast cancer. Design, Setting, and Participants Prospective study of 285526 women between the ages of 25 and 70 years, participating in the European Prospective Investigation Into Cancer and Nutrition (EPIC) study, recruited from 8 of the 10 participating European countries. Participants completed a dietary questionnaire in 1992-1998 and were followed up for incidence of cancer until 2002. Main Outcome Measures Relative risks for breast cancer by total and specific vegetable and fruit intake. Analyses were stratified by age at recruitment and study center. Relative risks were adjusted for established breast cancer risk factors. Results During 1486402 person-years (median duration of follow-up, 5.4 years), 3659 invasive incident breast cancer cases were reported. No significant associations between vegetable or fruit intake and breast cancer risk were observed. Relative risks for the highest vs the lowest quintile were 0.98 (95% confidence interval [CI], 0.84-1.14) for total vegetables, 1.09 (95% Cl, 0.94-1.25) for total fruit, and 1.05 (95% Cl, 0.92-1.20) for fruit and vegetable juices. For 6 specific vegetable subgroups no associations with breast cancer risk were observed either. Conclusion Although the period of follow-up is limited for now, the results suggest that total or specific vegetable and fruit intake is not associated with risk for breast cancer.
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11.
  • Vineis, P., et al. (författare)
  • Genetic susceptibility according to three metabolic pathways in cancers of the lung and bladder and in myeloid leukemias in nonsmokers
  • 2007
  • Ingår i: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 18:7, s. 1230-1242
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: We chose a set of candidate single nucleotide polymorphisms (SNPs) to investigate gene-environment interactions in three types of cancer that have been related to air pollution (lung, bladder and myeloid leukemia). Patients and methods: The study has been conducted as a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort (409 cancer cases and 757 matched controls). We included never and ex-smokers. SNPs were in genes involved in oxidative stress, phase I metabolizing genes, phase 11 metabolizing genes and methylenetetrahydrofolate reductase (MTHFR). Results: The most notable findings are: GSTM1 deletion and bladder cancer risk [odds ratio (OR) = 1.60; 95% confidence interval 1.00-2.56]; CYP1A1 and leukemia (2.22, 1.33-3.70; heterozygotes); CYP1B1 and leukemia (0.47, 0.27-0.84; homozygotes); MnSOD and leukemia (1.91, 1.08-3.38; homozygotes) and NQO1 and lung cancer (8.03, 1.73-37.3; homozygotes). Other statistically significant associations were found in subgroups defined by smoking habits (never or ex-smokers), environmental tobacco smoke or gender, with no obvious pattern. When gene variants were organized according to the three main pathways, the emerging picture was of a strong involvement of combined phase I enzymes in leukemia, with an OR of 5 (1.63-15.4) for those having three or more variant alleles. The association was considerably stronger for leukemias arising before the age of 55.
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  • Bamia, C, et al. (författare)
  • Dietary patterns among older Europeans: the EPIC-Elderly study
  • 2005
  • Ingår i: British Journal of Nutrition. - 1475-2662 .- 0007-1145. ; 94:1, s. 100-113
  • Tidskriftsartikel (refereegranskat)abstract
    • Overall dietary patterns have been associated with health and longevity. We used principal component (PC) and cluster analyses to identify the prevailing dietary patterns of 99 744 participants, aged 60 years or older, living in nine European countries and participating in the European Prospective Investigation into Cancer and Nutrition (EPIC-Elderly cohort) and to examine their socio-demographic and lifestyle correlates. Two PC were identified: PC1 reflects a 'vegetable-based' diet with an emphasis on foods of plant origin, rice, pasta and other grain rather than on margarine, potatoes and non-alcoholic beverages. PC2 indicates a 'sweet- and fat-dominated' diet with a preference for sweets, added fat and dairy products but not meat, alcohol, bread and eggs. PC1 was associated with a younger age, a higher level of education, physical activity, a higher BMI, a lower waist:hip ratio and never and past smoking. PC2 was associated with older age, less education, never having smoked, a lower BMI and waist:hip ratio and lower levels of physical activity. Elderly individuals in southern Europe scored positively on PC1 and about zero on PC2, whereas the elderly in northern Europe scored negatively on PC1 and variably on PC2. The results of cluster analysis were compatible with the indicated dietary patterns. 'Vegetable-based' and a 'sweet- and fat-dominated' diets are prevalent among the elderly across Europe, and there is a north-south gradient regarding their dietary choices. Our study contributes to the identification of groups of elderly who are likely to have different prospects for long-term disease occurrence and survival.
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  • Weikert, S, et al. (författare)
  • Blood Pressure and Risk of Renal Cell Carcinoma in the European Prospective Investigation into Cancer and Nutrition
  • 2008
  • Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 167:4, s. 438-446
  • Tidskriftsartikel (refereegranskat)abstract
    • Elevated blood pressure has been implicated as a risk factor for renal cell carcinoma (RCC), but prospective studies were confined to men and did not consider the effect of antihypertensive medication. The authors examined the relation among blood pressure, antihypertensive medication, and RCC in the European Prospective Investigation into Cancer and Nutrition (EPIC). Blood pressure was measured in 296,638 women and men, recruited in eight European countries during 1992-1998, 254,935 of whom provided information on antihypertensive medication. During a mean follow-up of 6.2 years, 250 cases of RCC were identified. Blood pressure was independently associated with risk of RCC. The relative risks for the highest versus the lowest category of systolic (>/=160 mmHg vs. <120 mmHg) and diastolic (>/=100 mmHg vs. <80 mmHg) blood pressures were 2.48 (95% confidence interval: 1.53, 4.02) and 2.34 (95% confidence interval: 1.54, 3.55). Risk estimates did not significantly differ according to sex or use of antihypertensive medication. Individuals taking antihypertensive drugs were not at a significantly increased risk unless blood pressure was poorly controlled. These results support the hypothesis that hypertension, rather than its medications, increases the risk of RCC in both sexes, while effective blood pressure control may lower the risk.
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  • Berglund, B, et al. (författare)
  • The Swedish Blood Pass project.
  • 2007
  • Ingår i: Scandinavian Journal of Medicine and Science in Sports. - : Wiley. - 0905-7188 .- 1600-0838. ; 17:3, s. 292-7
  • Tidskriftsartikel (refereegranskat)abstract
    • Manipulation of the blood's oxygen carrying capacity (CaO(2)) through reinfusion of red blood cells, injections of recombinant erythropoietin or by other means results in an increased maximal oxygen uptake and concomitantly enhanced endurance performance. Therefore, there is a need to establish a system--"A Blood Pass"--through which such illegal and unethical methods can be detected. Venous blood samples were taken under standardized conditions from 47 male and female Swedish national and international elite endurance athletes four times during the athletic year of the individual sport (beginning and end of the preparation period and at the beginning and during peak performance in the competition period). In these samples, different hematological values were determined. ON(hes) and OFF(hre) values were calculated according to the formula of Gore et al. A questionnaire regarding training at altitude, alcohol use and other important factors for hematological status was answered by the athletes. There were some individual variations comparing hematological values obtained at different times of the athletic year or at the same time in the athletic year but in different years. However, the median values of all individual hematological, ON(hes) and OFF(hre), values taken at the beginning and the end of the preparation or at the beginning and the end of the competition period, respectively, as well as median values for the preparation and competition periods in the respective sport, were all within the 95% confidence limit (CI) of each comparison. It must be mentioned that there was no gender difference in this respect. This study shows that even if there are some individual variations in different hematological values between different sampling times in the athletic year, median values of important hematological factors are stable over time. It must be emphasized that for each blood sample, the 95% CI in each athlete will be increasingly narrower. The conclusion is that there is a physiological basis for establishing an individual-based "Blood Pass" system, mainly for athletes competing at the international level. On indications of manipulations of hemoglobin concentration and red cell mass by deviations from established "Blood Pass" data, more specific methods can be applied.
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  • Birney, Ewan, et al. (författare)
  • Prepublication data sharing
  • 2009
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 461:7261, s. 168-170
  • Tidskriftsartikel (refereegranskat)abstract
    • Rapid release of prepublication data has served the field of genomics well. Attendees at a workshop in Toronto recommend extending the practice to other biological data sets.
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  • Glimelius, Bengt, et al. (författare)
  • A randomized phase III multicenter trial comparing irinotecan in combination with the Nordic bolus 5-FU and folinic acid schedule or the bolus/infused de Gramont schedule (Lv5FU2) in patients with metastatic colorectal cancer
  • 2008
  • Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 19:5, s. 909-914
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: To compare irinotecan with the Nordic 5-fluorouracil (5-FU) and folinic acid (FA) bolus schedule [irinotecan 180 mg/m2 on day 1, 5-FU 500 mg/m2 and FA 60 mg/m2 on day 1 and 2 (FLIRI)] or the Lv5FU2 schedule [irinotecan 180 mg/m2 on day 1, FA 200 mg/m2, 5-FU bolus 400 mg/m2 and infused 5-FU 600 mg/m2 on day 1 and 2 (Lv5FU2-IRI)] due to uncertainties about how to administrate 5-FU with irinotecan. Patients and methods: Patients (n = 567) with metastatic colorectal cancer were randomly assigned to receive FLIRI or Lv5FU2-IRI. Primary end point was progression-free survival (PFS). Results: Patient characteristics were well balanced. PFS did not differ between groups (median 9 months, P = 0.22). Overall survival (OS) was also similar (median 19 months, P = 0.9). Fewer objective responses were seen in the FLIRI group (35% versus 49%, P = 0.001) but the metastatic resection rate did not differ (4% versus 6%, P = 0.3). Grade 3/4 neutropenia (11% versus 5%, P = 0.01) and grade 2 alopecia (18% versus 9%, P = 0.002) were more common in the FLIRI group. The 60-day mortality was 2.4% versus 2.1%. Conclusions: Irinotecan with the bolus Nordic schedule (FLIRI) is a convenient treatment with PFS and OS comparable to irinotecan with the Lv5FU2 schedule. Neutropenia and alopecia are more prevalent, but both regimens are equally well tolerated. © The Author 2008. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
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26.
  • Jenab, M, et al. (författare)
  • Plasma and dietary carotenoid, retinol and tocopherol levels and the risk of gastric adenocarcinomas in the European prospective investigation into cancer and nutrition
  • 2006
  • Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 95:3, s. 406-415
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite declining incidence rates, gastric cancer (GC) is a major cause of death worldwide. Its aetiology may involve dietary antioxidant micronutrients such as carotenoids and tocopherols. The objective of this study was to determine the association of plasma levels of seven common carotenoids, their total plasma concentration, retinol and alpha- and gamma-tocopherol, with the risk of gastric adenocarcinoma in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 countries. A secondary objective was to determine the association of total sum of carotenoids, retinol and alpha-tocopherol on GCs by anatomical subsite (cardia/noncardia) and histological subtype (diffuse/intestinal). Analytes were measured by high-performance liquid chromatography in prediagnostic plasma from 244 GC cases and 645 controls matched by age, gender, study centre and date of blood donation. Conditional logistic regression models adjusted by body mass index, total energy intake, smoking and Helicobacter pylori infection status were used to estimate relative cancer risks. After an average 3.2 years of follow-up, a negative association with GC risk was observed in the highest vs the lowest quartiles of plasma beta-cryptoxanthin (odds ratio (OR) = 0.53, 95% confidence intervals (CI) = 0.30-0.94, P(trend) = 0.006), zeaxanthin (OR = 0.39, 95% CI = 0.22-0.69, P(trend) = 0.005), retinol (OR = 0.55, 95% CI = 0.33-0.93, P(trend) = 0.005) and lipid-unadjusted alpha-tocopherol (OR = 0.59, 95% CI = 0.37-0.94, P(trend) = 0.022). For all analytes, no heterogeneity of risk estimates or significant associations were observed by anatomical subsite. In the diffuse histological subtype, an inverse association was observed with the highest vs lowest quartile of lipid-unadjusted alpha-tocopherol (OR = 0.26, 95% CI = 0.11-0.65, P(trend) = 0.003). These results show that higher plasma concentrations of some carotenoids, retinol and alpha-tocopherol are associated with reduced risk of GC.
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  • Vaissière, Thomas, et al. (författare)
  • Quantitative analysis of DNA methylation after whole bisulfitome amplification of a minute amount of DNA from body fluids.
  • 2009
  • Ingår i: Epigenetics : official journal of the DNA Methylation Society. - 1559-2308. ; 4:4, s. 221-30
  • Tidskriftsartikel (refereegranskat)abstract
    • Cell-free circulating DNA isolated from the plasma of individuals with cancer has been shown to harbor cancer-associated changes in DNA methylation, and thus it represents an attractive target for biomarker discovery. However, the reliable detection of DNA methylation changes in body fluids has proven to be technically challenging. Here we describe a novel combination of methods that allows quantitative and sensitive detection of DNA methylation in minute amounts of DNA present in body fluids (quantitative Methylation Analysis of Minute DNA amounts after whole Bisulfitome Amplification, qMAMBA). This method involves genome-wide amplification of bisulphite-modified DNA template followed by quantitative methylation detection using pyrosequencing and allows analysis of multiple genes from a small amount of starting DNA. To validate our method we used qMAMBA assays for four genes and LINE1 repetitive sequences combined with plasma DNA samples as a model system. qMAMBA offered high efficacy in the analysis of methylation levels and patterns in plasma samples with extremely small amounts of DNA and low concentrations of methylated alleles. Therefore, qMAMBA will facilitate methylation studies aiming to discover epigenetic biomarkers, and should prove particularly valuable in profiling a large sample series of body fluids from molecular epidemiology studies as well as in tracking disease in early diagnostics.
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  • Alzari, Pedro M., et al. (författare)
  • Implementation of semi-automated cloning and prokaryotic expression screening : the impact of SPINE
  • 2006
  • Ingår i: Acta Crystallographica Section D. - 0907-4449 .- 1399-0047. ; 62, s. 1103-1113
  • Tidskriftsartikel (refereegranskat)abstract
    • The implementation of high- throughput ( HTP) cloning and expression screening in Escherichia coli by 14 laboratories in the Structural Proteomics In Europe ( SPINE) consortium is described. Cloning efficiencies of greater than 80% have been achieved for the three non- ligation- based cloning techniques used, namely Gateway, ligation- indendent cloning of PCR products ( LIC- PCR) and In- Fusion, with LIC- PCR emerging as the most cost- effective. On average, two constructs have been made for each of the approximately 1700 protein targets selected by SPINE for protein production. Overall, HTP expression screening in E. coli has yielded 32% soluble constructs, with at least one for 70% of the targets. In addition to the implementation of HTP cloning and expression screening, the development of two novel technologies is described, namely library- based screening for soluble constructs and parallel small- scale high- density fermentation.
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30.
  • Berglund, Birgitta, et al. (författare)
  • Measuring odor quality of building materials in an odor space
  • 2009
  • Ingår i: Fechner Day 2009. - Galway, Irland : International Society for Psychophysics. ; , s. 221-226
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • We can discriminate a huge number of odors. Still, the perceptual mechanisms responsible for perceived odor quality is not well understood. The research goal was to define an odor reference space that may represent indoor air quality. Two observers scaled the perceived similarity of discernable emissions of all possible pairs of 30 building materials. Combined cluster and component analyses were used for identifying 12 potential odor references enabling a preliminary definition of the odor space. This odor space was partially validated and improved by individual differences scaling (INDSCAL) of seven observers’ similarity matrices of odor qualities including 27 of the 30 building materials. Grounded in 13 odor references, a three-dimensional measurement space is provided for odor quality of building materials emissions and potentially also for the indoor air quality of non-industrial buildings.
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38.
  • Botteldooren, D, et al. (författare)
  • Experimental investigation of noise annoyance caused by high-speed trains.
  • 2005
  • Ingår i: ICSV 2005–Twelfth International Congress on Sound and Vibration. - : IIAV/CAPS-IST, Lissabon.
  • Bokkapitel (refereegranskat)abstract
    • The difference in perceived noise annoyance caused by train and highway noise at the same averaged noise level, has led to the introduction of the ’railway bonus’. This bonus has found its way to the noise legislation in many countries, leading to more relaxed restrictions on time averaged noise levels, LAeq. With the introduction of high-speed trains and train-like transportation systems based on magnetic levitation, the question has risen whether the railway bonus can still be applied. The paper reports on an experiment that was conducted to answer this question. The experiment that was performed was different from previous efforts in many ways. Most importantly, the experiment was conducted in a realistic setting, a holiday cottage, and participants were asked to engage in light daily activities such as reading a magazine during the tests. Traffic noise was reproduced in an ecologically valid way, using outdoor loudspeakers. Every ten minutes the participants were asked to judge noise annoyance. At the beginning of the experiment and after about 1.5 hours the participants were also asked to rate a set of 7 master scaling sounds. After this experiment, a more conventional listening test was conducted using 45-s excerpts. The experiment was also unique in the way that 100 participants were selected to be representative for the Dutch population. The selection procedure involved careful screening based on a survey that was administered at the doorstep of 1500 persons’ homes.
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39.
  • Botteldooren, D., et al. (författare)
  • Modelling the role of attention in the assessment of environmental noise annoyance
  • 2008
  • Ingår i: Proceedings of the 9th International Congress on Noise as a Public Health Problem (ICBEN), Foxwoods, CT, USA.
  • Konferensbidrag (refereegranskat)abstract
    • Community noise effects in general and noise annoyance in particular are mostly studied by relating them to exposure through blind statistical analyses of large datasets. This paper reports on a specific part of a quite different approach. using mathematical simulation of basic perception and psychophysical mechanisms for a large synthetic population. Insight is sought into the mechanisms underlying the emergence of noise effects. This is achieved by comparing–in a phenomenological way–the statistics of the data gathered from the simulated synthetic population in that of the real population. This paper focuses on modeling the role of attention. Attention could play a role in two distinct aspects of the process: firstly, attention can be drawn away from other tasks by the environmental sound or tasks requiring sustained attention can suppress the noticing of the environmental sound; secondly, attention can jump between sounds in multisource sonic environments. In modeling this dual role of attention, care must be taken to simplify existing knowledge on theses aspects of perception in such a way that the model can be used to study long exposure times and large populations. Such modeling may support the assessment of real life situation where multiple environmental sounds interfere and cause noise annoyance. Example simulations involving exposure to railway noise, road traffic noise, and natural sound produced by the individual's own activity show the influence of attention on the model outcome.
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40.
  • Botteldooren, D, et al. (författare)
  • Perceived Noise Annoyance Caused by Maglev Trains : Final Scientific Report
  • 2005
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • The underlying study aimed at quantifying the impact of sound caused by high speed magnetic levitation transport systems on perceived noise annoyance in a realistic setting. An innovative system was implemented for selecting representative participants from the Dutch population, as regards age, gender, level of education noise sensitivity reported anxiety, pre-exposure to train and road traffic noise, general quality of the living environment, and general health. It was grounded in 1500 participants’ responses to a specifically constructed questionnaire, which contained items from a nation-wide Dutch and Eurobarometer surveys. Finally 80 (+21) representative participants were selected. During the experiment, which took place in a realistic setting (living room of holiday cottage), groups of 5-7 participants were asked to be seated, relax, reading a magazine or newspaper and were served refreshments. During their stay, traffic noise was reproduced in an ecologically valid way in outdoor loudspeakers. Every 10 min, the participants were asked to assess traffic noise annoyance. At the beginning and after at least 1 hour of the experiment, participants were also asked to scale the annoyance of a set of 7 reference sounds utilized for master scaling. Based on this study, we found that there is no evidence to expect a significant difference in noise annoyance caused by Maglev and TGV trains at the same average façade exposure. Noise annoyance caused by conventional trains was not found to be significantly lower than annoyance caused by these high-speed trains at the same average façade exposure (tested up to 65 dB(A) only). The latter conclusion is in contradiction with earlier work by Vos et al. A comparison to the work of Neugebauer at al. came out inconclusive: although these authors state there is a distinct difference between the two types of trains investigated, their actual results fall within the spread of annoyance levels due to distance to the track and vehicle speed that we observed. Field surveys have shown that for the same average sound level, railway noise causes less annoyance than dense road traffic noise, at least for certain interval of levels. Although our study included several of the factors that may contribute to this effect, we could not observe it, except when the results were limited to sounds recorded at a distance of over 100 m.
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41.
  • Botteldooren, D, et al. (författare)
  • Perceived Noise Annoyance Caused by Maglev Trains. Management Summary.
  • 2005
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • The annoyance impact in realistic settings of traffic noise was assessed for one, two or four train passages, primarily high-speed trains, or continuous road traffic noise. An innovative system for selecting representative participants from the Dutch population was implemented, as regards a number of critical variables (age, gender, level of education, noise sensitivity, reported anxiety, home exposure to train and road traffic noise, general quality of living environment, and general health). In total, 1500 candidate participants responded to the specifically constructed questionnaire with items from a nation-wide Dutch survey and the Eurobarometer. Participants with typical Dutch response profile were recruited on a first come, first serve basis (in total 80 plus 21 extra persons. In the experiment, 5-7 participants were seated to be relaxed and to be reading a magazine or newspaper. The were served refreshments. Traffic noise was reproduced in outdoor loudspeakers in an ecologically valid way. Every 10 min, participants were asked to assess noise annoyance. At the beginning and at brief intervals during the experiment, participants assessed the annoyance of a set of 7 reference sounds utilized for master scaling. At the same average façade exposure, no significant annoyance difference was neither found for Maglev and TGV, nor for conventional trains and the high-speed trains (only tested up to 65 dBA). The latter result contradicts Vos et al.’s earlier findings. Neugebauer at al.’s results fall within the spread in annoyance values due to distance to the track and vehicle speed that we observed. Field surveys have shown that for the same average sound level, railway noise evokes less annoyance than dense road traffic noise, at least for a certain interval of levels. Although our experiment included several of the factors that may contribute to this effect, we were unable to observe this kind of effect, except for the case when the sounds were recorded at a distance of more than 100 m.
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43.
  • Brådvik, Louise, et al. (författare)
  • Self-reported and observed heroin overdoses in Malmoe
  • 2007
  • Ingår i: Journal of Substance Use. - : Informa UK Limited. - 1465-9891 .- 1475-9942. ; 12:2, s. 119-126
  • Tidskriftsartikel (refereegranskat)abstract
    • Object: The aim of the present study was to investigate the pattern of non-fatal heroin overdoses for men and women in Sweden, a country with late onset of heroin use. Material: Subjects were recruited through the Syringe Programme and the Addiction Centre in Malmoe. A total of 149 subjects were interviewed, 108 men and 41 women. They were asked about their social situation, experienced and observed overdoses and circumstances around them. Results: Overdoses were very common; 74% of the subjects had experienced at least one overdose. Almost all, 96%, had observed at least one overdose in others and 32% had witnessed a fatal overdose. Actions taken were often insufficient. A combination with other drugs, mainly benzodiazepine and alcohol and/or a lowered tolerance for heroin after visits in institutions contributed to the overdose in a majority of the cases. Men and women differed in that men used concomitant drugs more often and women more often took heroin alone. Conclusion: Self-reported and observed non-fatal heroin overdoses were more common than expected. Contributing factors were found in the majority of the cases. Pure overdoses were more common in women.
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47.
  • Feigelson, HS, et al. (författare)
  • Haplotype analysis of the HSD17B1 gene and risk of breast cancer: A comprehensive approach to multicenter analyses of prospective cohort studies
  • 2006
  • Ingår i: Cancer Research. - 1538-7445. ; 66:4, s. 2468-2475
  • Tidskriftsartikel (refereegranskat)abstract
    • The 17 beta-hydroxysteroid dehydrogenase 1 gene (HSD17B1) encodes 17HSD1, which catalyzes the final step of estradiol biosynthesis. Despite the important role of HSD17B1 in hormone metabolism, few epidemiologic studies of HSD17B1 and breast cancer have been conducted. This study includes 5,370 breast cancer cases and 7,480 matched controls from five large cohorts in the Breast and Prostate Cancer Cohort Consortium. We characterized variation in HSD17B1 by resequencing and dense genotyping a multiethnic sample and identified haplotype-tagging single nucleotide polymorphisms (htSNP) that capture common variation within a 33.3-kb region around HSD17B1. Four htSNPs, including the previously studied SNP rs605059 (S312G), were genotyped to tag five common haplotypes in all cases and controls. Conditional logistic regression was used to estimate odds ratios (OR) for disease. We found no evidence of association between common HSD17B1 haplotypes or htSNPs and overall risk of breast cancer. The OR for each haplotype relative to the most common haplotype ranged from 0.98 to 1.07 (omnibus test for association: X-2 = 3.77, P = 0.58, 5 degrees of freedom). When cases were subdivided by estrogen receptor (ER) status, two common haplotypes were associated with ER-negative tumors (test for trend, Ps = 0.0009 and 0.0076; n = 353 cases). HSD17B1 variants that are common in Caucasians are not associated with overall risk of breast cancer; however, there was an association among the subset of ER-negative tumors. Although the probability that these ER-negative findings are false-positive results is high, these findings were consistent across each cohort examined and warrant further study.
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48.
  • Florez, J. C., et al. (författare)
  • Association testing of common variants in the insulin receptor substrate-1 gene (IRS1) with type 2 diabetes
  • 2007
  • Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 50:6, s. 1209-1217
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims/hypothesis Activation of the insulin receptor substrate-1 (IRS1) is a key initial step in the insulin signalling pathway. Despite several reports of association of the G972R polymorphism in its gene IRS1 with type 2 diabetes, we and others have not observed this association in well-powered samples. However, other nearby variants might account for the putative association signal. Subjects and methods We characterised the haplotype map of IRS1 and selected 20 markers designed to capture common variations in the region. We genotyped this comprehensive set of markers in several family-based and case-control samples of European descent totalling 12,129 subjects. Results In an initial sample of 2,235 North American and Polish case-control pairs, the minor allele of the rs934167 polymorphism showed nominal evidence of association with type 2 diabetes (odds ratio [OR] 1.25, 95% CI 1.03-1.51, p=0.03). This association showed a trend in the same direction in 7,659 Scandinavian samples (OR 1.16, 95% CI 0.96-1.39, p=0.059). The combined OR was 1.20 (p=0.008), but statistical correction for the number of variants examined yielded a p value of 0.086. We detected no differences across rs934167 genotypes in insulin-related quantitative traits. Conclusion/interpretation Our data do not support an association of common variants in IRS1 with type 2 diabetes in populations of European descent.
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