| 181. |
- Ritte, Rebecca, et al.
(författare)
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Adiposity, hormone replacement therapy use and breast cancer risk by age and hormone receptor status : a large prospective cohort study.
- 2012
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Ingår i: Breast cancer research : BCR. - London : BioMed Central. - 1465-542X. ; 14:3, s. R76-
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: INTRODUCTION: Associations of hormone-receptor positive breast cancer with excess adiposity are reasonably well characterized; however, uncertainty remains regarding the association of body mass index (BMI) with hormone-receptor negative malignancies, and possible interactions by hormone replacement therapy (HRT) use. METHODS: Within the European EPIC cohort, Cox proportional hazards models were used to describe the relationship of BMI, waist and hip circumferences with risk of estrogen-receptor (ER) negative and progesterone-receptor (PR) negative (n = 1,021) and ER+PR+ (n = 3,586) breast tumors within five-year age bands. Among postmenopausal women, the joint effects of BMI and HRT use were analyzed. RESULTS: For risk of ER-PR- tumors, there was no association of BMI across the age bands. However, when analyses were restricted to postmenopausal HRT never users, a positive risk association with BMI (third versus first tertile HR = 1.47 (1.01 to 2.15)) was observed. BMI was inversely associated with ER+PR+ tumors among women aged ≤49 years (per 5 kg/m2 increase, HR = 0.79 (95%CI 0.68 to 0.91)), and positively associated with risk among women ≥65 years (HR = 1.25 (1.16 to 1.34)). Adjusting for BMI, waist and hip circumferences showed no further associations with risks of breast cancer subtypes. Current use of HRT was significantly associated with an increased risk of receptor-negative (HRT current use compared to HRT never use HR: 1.30 (1.05 to 1.62)) and positive tumors (HR: 1.74 (1.56 to 1.95)), although this risk increase was weaker for ER-PR- disease (Phet = 0.035). The association of HRT was significantly stronger in the leaner women (BMI ≤22.5 kg/m2) than for more overweight women (BMI ≥25.9 kg/m2) for, both, ER-PR- (HR: 1.74 (1.15 to 2.63)) and ER+PR+ (HR: 2.33 (1.84 to 2.92)) breast cancer and was not restricted to any particular HRT regime. CONCLUSIONS: An elevated BMI may be positively associated with risk of ER-PR- tumors among postmenopausal women who never used HRT. Furthermore, postmenopausal HRT users were at an increased risk of ER-PR- as well as ER+PR+ tumors, especially among leaner women. For hormone-receptor positive tumors, but not for hormone-receptor negative tumors, our study confirms an inverse association of risk with BMI among young women of premenopausal age. Our data provide evidence for a possible role of sex hormones in the etiology of hormone-receptor negative tumors.
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| 182. |
- Rohrmann, S., et al.
(författare)
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Smoking and the risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition
- 2013
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 108:3, s. 708-714
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Tidskriftsartikel (refereegranskat)abstract
- Background: Smoking is not associated with prostate cancer incidence in most studies, but associations between smoking and fatal prostate cancer have been reported. Methods: During 1992 and 2000, lifestyle information was assessed via questionnaires and personal interview in a cohort of 145112 European men. Until 2009, 4623 incident cases of prostate cancer were identified, including 1517 cases of low-grade, 396 cases of high grade, 1516 cases of localised, 808 cases of advanced disease, and 432 fatal cases. Multivariable Cox proportional hazards regression models were used to examine the association of smoking status, smoking intensity, and smoking duration with the risk of incident and fatal prostate cancer. Results: Compared with never smokers, current smokers had a reduced risk of prostate cancer (RR = 0.90, 95% CI: 0.83-0.97), which was statistically significant for localised and low-grade disease, but not for advanced or high-grade disease. In contrast, heavy smokers (25+ cigarettes per day) and men who had smoked for a long time (40+ years) had a higher risk of prostate cancer death (RR = 1.81, 95% CI: 1.11-2.93; RR = 1.38, 95% CI: 1.01-1.87, respectively). Conclusion: The observation of an increased prostate cancer mortality among heavy smokers confirms the results of previous prospective studies.
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| 183. |
- Ros, Martine M., et al.
(författare)
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Fruit and vegetable consumption and risk of aggressive and non-aggressive urothelial cell carcinomas in the European Prospective Investigation into Cancer and Nutrition
- 2012
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 48:17, s. 3267-3277
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Tidskriftsartikel (refereegranskat)abstract
- Background: Many epidemiological studies have examined fruit and vegetable consumption in relation to the risk of urothelial cell carcinoma (UCC) of the bladder, but results are inconsistent. The association between fruit and vegetable consumption and UCC risk may vary by bladder tumour aggressiveness. Therefore, we examined the relation between fruit and vegetable consumption and the risk of aggressive and non-aggressive UCC in the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods: After 8.9 years of follow-up, 947 UCC were diagnosed among 468,656 EPIC participants. Of these, 421 could be classified as aggressive UCC and 433 as non-aggressive UCC cases. At recruitment, fruit and vegetable consumption was assessed by validated dietary questionnaires. Multivariable hazard ratios were estimated using Cox regression stratified by age, sex and center and adjusted for smoking status, duration and intensity of smoking, and energy intake. Results: Total consumption of fruits and vegetables was not associated with aggressive UCC nor with non-aggressive UCC. A 25 g/day increase in leafy vegetables and grapes consumption was associated with a reduced risk of non-aggressive UCC (hazard ratio (HR) 0.88; 95% confidence interval (CI) 0.78-1.00 and HR 0.87; 95% CI 0.77-0.98, respectively), while the intake of root vegetables was inversely associated with risk of aggressive UCC (HR 0.87; 95% CI 0.77-0.98). Conclusion: Our study did not confirm a protective effect of total fruit and/or vegetable consumption on aggressive or non-aggressive UCC. High consumption of certain types of vegetables and of fruits may reduce the risk of aggressive or non-aggressive UCC; however chance findings cannot be excluded. (C) 2012 Elsevier Ltd. All rights reserved.
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| 184. |
- Saaka, Yussif, et al.
(författare)
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Characterisation of the apparent aqueous solubility enhancement of testosterone analogues in micelles of dodecyl-chained surfactants with different headgroups
- 2023
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Ingår i: Journal of Molecular Liquids. - 0167-7322. ; 385
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Tidskriftsartikel (refereegranskat)abstract
- The solubilisation capacities of the micelles formed by a range of surfactants possessing a dodecyl (C12) hydrocarbon ‘tail’ and a variety of hydrophilic ‘headgroups’ have been studied for a range of hydrophobic steroids (testosterone (T) and its propionate (TP) and enanthate (TE) esters). The solubilisation studies were performed at ambient temperature, with drug concentration monitored (over 48–72 h) by UV absorbance. The various surfactant systems were characterised in terms of their physicochemical properties, including their surface tension, critical micelle concentration, viscosity, and density. Results show that while the apparent aqueous solubility of the poorly water-soluble steroids increases upon solubilisation within the surfactant micelles, the extent of this increase varies with the nature of the hydrophilic headgroup and the hydrophobicity of the drug. Specifically, changing the surfactant headgroup from non-ionic to zwitterionic, then to ionic, results in a marked increase in solubility of the two least hydrophobic steroids, testosterone and testosterone propionate, suggesting rather counter-intuitively that these steroidal drugs tend to associate to a greater extent with micelles formed by surfactants with more hydrophilic/charged head groups. The more hydrophobic steroid, TE, was solubilised to the greatest extent, being predominantly solubilised within the micelle core. In this case, the influence of surfactant head group on TE solubilisation was less obvious, with surfactants containing ionic and zwitterionic head groups exhibiting high levels of solubilisation. The physicochemical properties that had most influence on solubilisation of the testosterone analogues, as evaluated using multiple linear regression, were micelle shape for T and TP, and critical micelle concentration for TE. Through the findings of this comparative study, the essential molecular descriptors of optimal solubilisation for improved drug delivery and the loci of solubilisation of the testosterone analogues have been identified.
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| 185. |
- Scown, Murray W., et al.
(författare)
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Towards a global sustainable development agenda built on social-ecological resilience
- 2023
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Ingår i: Global Sustainability. - 2059-4798. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Non-technical summary The United Nations' sustainable development goals (SDGs) articulate societal aspirations for people and our planet. Many scientists have criticised the SDGs and some have suggested that a better understanding of the complex interactions between society and the environment should underpin the next global development agenda. We further this discussion through the theory of social-ecological resilience, which emphasises the ability of systems to absorb, adapt, and transform in the face of change. We determine the strengths of the current SDGs, which should form a basis for the next agenda, and identify key gaps that should be filled. Technical summary The United Nations' sustainable development goals (SDGs) are past their halfway point and the next global development agenda will soon need to be developed. While laudable, the SDGs have received strong criticism from many, and scholars have proposed that adopting complex adaptive or social-ecological system approaches would increase the effectiveness of the agenda. Here we dive deeper into these discussions to explore how the theory of social-ecological resilience could serve as a strong foundation for the next global sustainable development agenda. We identify the strengths and weaknesses of the current SDGs by determining which of the 169 targets address each of 43 factors affecting social-ecological resilience that we have compiled from the literature. The SDGs with the strongest connections to social-ecological resilience are the environment-focus goals (SDGs 2, 6, 13, 14, 15), which are also the goals consistently under-prioritised in the implementation of the current agenda. In terms of the 43 factors affecting social-ecological resilience, the SDG strengths lie in their communication, inclusive decision making, financial support, regulatory incentives, economic diversity, and transparency in governance and law. On the contrary, ecological factors of resilience are seriously lacking in the SDGs, particularly with regards to scale, cross-scale interactions, and non-stationarity. Social media summary The post-2030 agenda should build on strengths of SDGs 2, 6, 13, 14, 15, and fill gaps in scale, variability, and feedbacks.
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| 186. |
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| 187. |
- Segal, Eran, et al.
(författare)
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Building an international consortium for tracking coronavirus health status
- 2020
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 26:8, s. 1161-1165
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- We call upon the research community to standardize efforts to use daily self-reported data about COVID-19 symptoms in the response to the pandemic and to form a collaborative consortium to maximize global gain while protecting participant privacy.
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| 188. |
- Sinilnikova, Olga M., et al.
(författare)
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Haplotype-based analysis of common variation in the acetyl-CoA carboxyiase alpha gene and breast cancer risk: A case-control study nested within the European prospective investigation into cancer and nutrition
- 2007
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Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755. ; 16:3, s. 409-415
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Tidskriftsartikel (refereegranskat)abstract
- A key fatty acid synthesis enzyme, acetyl-CoA carboxylase alpha(ACC-alpha), has been shown to be highly expressed in human breast cancer and other tumor types and also to specifically interact with the protein coded by one of two major breast cancer susceptibility genes BRCA1. We used a comprehensive haplotype analysis to examine the contribution of the ACC-alpha common genetic variation (allele frequency > 5%) to breast cancer in a case-control study (1,588 cases/2,600 controls) nested within the European Prospective Investigation into Cancer and Nutrition. We identified 21 haplotypetagging polymorphisms efficiently capturing common variation within 325 kb of ACC-alpha and surrounding sequences using genotype data from the HapMap project and our resequencing data. We found an effect on overall risk of breast cancer in homozygous carriers of one common haplotype [odds ratio (OR), 1.74; 95% confidence interval (95% CI), 1.03-2.94]. When the data were subdivided by menopausal status, we found statistical evidence of heterogeneity for two other common haplotypes (P value for heterogeneity = 0.016 and 0.045). In premenopausal women, the carriers of these haplotypes, compared with noncarriers, had an altered risk of breast cancer (OR, 0.70; 95% CI, 0.53-0.92 and OR, 1.35; 95% CI, 1.04-1.76). These findings were not significant after adjustment for multiple testing and therefore should be considered as preliminary and evaluated in larger independent studies. However, they suggest a possible role of the ACC-alpha common sequence variants in susceptibility to breast cancer and encourage studies of other genes involved in fatty acid synthesis.
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| 189. |
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| 190. |
- Smith, Gustav, et al.
(författare)
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The Impact of Ancestry and Common Genetic Variants on QT Interval in African Americans.
- 2012
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Ingår i: Circulation: Cardiovascular Genetics. - 1942-325X. ; 5:6, s. 647-655
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: -Ethnic differences in cardiac arrhythmia incidence have been reported, with a particularly high incidence of sudden cardiac death (SCD) and low incidence of atrial fibrillation in individuals of African ancestry. We tested the hypotheses that African ancestry and common genetic variants are associated with prolonged duration of cardiac repolarization, a central pathophysiological determinant of arrhythmia, as measured by the electrocardiographic QT interval. METHODS AND RESULTS: -First, individual estimates of African and European ancestry were inferred from genome-wide single nucleotide polymorphism (SNP) data in seven population-based cohorts of African Americans (n=12 097) and regressed on measured QT interval from electrocardiograms. Second, imputation was performed for 2.8 million SNPs and a genome-wide association (GWA) study of QT interval performed in ten cohorts (n=13 105). There was no evidence of association between genetic ancestry and QT interval (p=0.94). Genome-wide significant associations (p<2.5x10(-8)) were identified with SNPs at two loci, upstream of the genes NOS1AP (rs12143842, p=2x10(-15)) and ATP1B1 (rs1320976, p=2x10(-10)). The most significant SNP in NOS1AP was the same as the strongest SNP previously associated with QT interval in individuals of European ancestry. Low p-values (p<10(-5)) were observed for SNPs at several other loci previously identified in GWA studies in individuals of European ancestry, including KCNQ1, KCNH2, LITAF and PLN. CONCLUSIONS: -We observed no difference in duration of cardiac repolarization with global genetic indices of African ancestry. In addition, our GWA study extends the association of polymorphisms at several loci associated with repolarization in individuals of European ancestry to include African Americans.
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