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Sökning: WFRF:(Byrnes A)

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1.
  • Romagnoni, A, et al. (författare)
  • Comparative performances of machine learning methods for classifying Crohn Disease patients using genome-wide genotyping data
  • 2019
  • Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 10351-
  • Tidskriftsartikel (refereegranskat)abstract
    • Crohn Disease (CD) is a complex genetic disorder for which more than 140 genes have been identified using genome wide association studies (GWAS). However, the genetic architecture of the trait remains largely unknown. The recent development of machine learning (ML) approaches incited us to apply them to classify healthy and diseased people according to their genomic information. The Immunochip dataset containing 18,227 CD patients and 34,050 healthy controls enrolled and genotyped by the international Inflammatory Bowel Disease genetic consortium (IIBDGC) has been re-analyzed using a set of ML methods: penalized logistic regression (LR), gradient boosted trees (GBT) and artificial neural networks (NN). The main score used to compare the methods was the Area Under the ROC Curve (AUC) statistics. The impact of quality control (QC), imputing and coding methods on LR results showed that QC methods and imputation of missing genotypes may artificially increase the scores. At the opposite, neither the patient/control ratio nor marker preselection or coding strategies significantly affected the results. LR methods, including Lasso, Ridge and ElasticNet provided similar results with a maximum AUC of 0.80. GBT methods like XGBoost, LightGBM and CatBoost, together with dense NN with one or more hidden layers, provided similar AUC values, suggesting limited epistatic effects in the genetic architecture of the trait. ML methods detected near all the genetic variants previously identified by GWAS among the best predictors plus additional predictors with lower effects. The robustness and complementarity of the different methods are also studied. Compared to LR, non-linear models such as GBT or NN may provide robust complementary approaches to identify and classify genetic markers.
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  • Cozen, W., et al. (författare)
  • A meta-analysis of Hodgkin lymphoma reveals 19p13.3 TCF3 as a novel susceptibility locus
  • 2014
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5, s. 3856-
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent genome-wide association studies (GWAS) of Hodgkin lymphoma (HL) have identified associations with genetic variation at both HLA and non-HLA loci; however, much of heritable HL susceptibility remains unexplained. Here we perform a meta-analysis of three HL GWAS totaling 1,816 cases and 7,877 controls followed by replication in an independent set of 1,281 cases and 3,218 controls to find novel risk loci. We identify a novel variant at 19p13.3 associated with HL (rs1860661; odds ratio (OR) = 0.81, 95% confidence interval (95% CI) = 0.76-0.86, P-combined 3.5 x 10(-10)), located in intron 2 of TCF3 (also known as E2A), a regulator of B-and T-cell lineage commitment known to be involved in HL pathogenesis. This meta-analysis also notes associations between previously published loci at 2p16, 5q31, 6p31, 8q24 and 10p14 and HL subtypes. We conclude that our data suggest a link between the 19p13.3 locus, including TCF3, and HL risk.
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  • Craddock, Nick, et al. (författare)
  • Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
  • 2010
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 713-720
  • Tidskriftsartikel (refereegranskat)abstract
    • Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed,19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated similar to 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
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  • Tsilidis, K. K., et al. (författare)
  • Oral contraceptives, reproductive history and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition
  • 2010
  • Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 103:11, s. 1755-1759
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Oral contraceptive use and reproductive factors may initiate long-term changes to the hormonal milieu and thereby, possibly influence colorectal cancer risk. METHODS: We examined the association of hormonal and reproductive factors with risk of colorectal cancer among 337 802 women in the European Prospective Investigation into Cancer and Nutrition, of whom 1878 developed colorectal cancer. RESULTS: After stratification for center and age, and adjustment for body mass index, smoking, diabetes mellitus, physical activity and alcohol consumption, ever use of oral contraceptives was marginally inversely associated with colorectal cancer risk (hazard ratio (HR), 0.92; 95% confidence interval (CI), 0.83-1.02), although this association was stronger among post-menopausal women (HR, 0.84; 95% CI: 0.74-0.95). Duration of oral contraceptive use and reproductive factors, including age at menarche, age at menopause, type of menopause, ever having an abortion, parity, age at first full-term pregnancy and breastfeeding, were not associated with colorectal cancer risk. CONCLUSION: Our findings provide limited support for a potential inverse association between oral contraceptives and colorectal cancer risk. British Journal of Cancer (2010) 103, 1755-1759. doi:10.1038/sj.bjc.6605965 www.bjcancer.com Published online 2 November 2010 (C) 2010 Cancer Research UK
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  • Moskal, A., et al. (författare)
  • Main nutrient patterns and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition study
  • 2016
  • Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 115:11, s. 1430-1440
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Much of the current literature on diet-colorectal cancer (CRC) associations focused on studies of single foods/nutrients, whereas less is known about nutrient patterns. We investigated the association between major nutrient patterns and CRC risk in participants of the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Methods: Among 477 312 participants, intakes of 23 nutrients were estimated from validated dietary questionnaires. Using results from a previous principal component (PC) analysis, four major nutrient patterns were identified. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed for the association of each of the four patterns and CRC incidence using multivariate Cox proportional hazards models with adjustment for established CRC risk factors. Results: During an average of 11 years of follow-up, 4517 incident cases of CRC were documented. A nutrient pattern characterised by high intakes of vitamins and minerals was inversely associated with CRC (HR per 1 s.d. = 0.94, 95% CI: 0.92-0.98) as was a pattern characterised by total protein, riboflavin, phosphorus and calcium (HR (1 s.d.) = 0.96, 95% CI: 0.93-0.99). The remaining two patterns were not significantly associated with CRC risk. Conclusions: Analysing nutrient patterns may improve our understanding of how groups of nutrients relate to CRC.
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  • Buchner, F. L., et al. (författare)
  • Fruits and vegetables consumption and the risk of histological subtypes of lung cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)
  • 2010
  • Ingår i: Cancer Causes and Control. - : Springer Science and Business Media LLC. - 1573-7225 .- 0957-5243. ; 21:3, s. 357-371
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To examine the association between fruit and vegetable consumption and risk of different histological subtypes of lung cancer among participants of the European Prospective Investigation into Cancer and Nutrition study. Methods Multivariable Cox proportional hazard models were used to analyze the data. A calibration study in a subsample was used to reduce dietary measurement errors. Results During a mean follow-up of 8.7 years, 1,830 incident cases of lung cancer (574 adenocarcinoma, 286 small cell, 137 large cell, 363 squamous cell, 470 other histologies) were identified. In line with our previous conclusions, we found that after calibration a 100 g/day increase in fruit and vegetables consumption was associated with a reduced lung cancer risk (HR 0.94; 95% CI 0.89-0.99). This was also seen among current smokers (HR 0.93; 95% CI 0.90-0.97). Risks of squamous cell carcinomas in current smokers were reduced for an increase of 100 g/day of fruit and vegetables combined (HR 0.85; 95% CI 0.76-0.94), while no clear effects were seen for the other histological subtypes. Conclusion We observed inverse associations between the consumption of vegetables and fruits and risk of lung cancer without a clear effect on specific histological subtypes of lung cancer. In current smokers, consumption of vegetables and fruits may reduce lung cancer risk, in particular the risk of squamous cell carcinomas.
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  • Carr, S.B., et al. (författare)
  • Factors associated with clinical progression to severe COVID-19 in people with cystic fibrosis: A global observational study
  • 2022
  • Ingår i: Journal of Cystic Fibrosis. - : Elsevier BV. - 1569-1993. ; 21:4, s. E221-E231
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: This international study aimed to characterise the impact of acute SARS-CoV-2 infection in people with cystic fibrosis and investigate factors associated with severe outcomes. Methods Data from 22 countries prior to 13th December 2020 and the introduction of vaccines were included. It was de-identified and included patient demographics, clinical characteristics, treatments, outcomes and sequalae following SARS-CoV-2 infection. Multivariable logistic regression was used to investigate factors associated with clinical progression to severe COVID-19, using the primary outcome of hospitalisation with supplemental oxygen. Results: SARS-CoV-2 was reported in 1555 people with CF, 1452 were included in the analysis. One third were aged <18 years, and 9.4% were solid-organ transplant recipients. 74.5% were symptomatic and 22% were admitted to hospital. In the non-transplanted cohort, 39.5% of patients with ppFEV1<40% were hospitalised with oxygen verses 3.2% with ppFEV >70%: a 17-fold increase in odds. Worse outcomes were independently associated with older age, non-white race, underweight body mass index, and CF-related diabetes. Prescription of highly effective CFTR modulator therapies was associated with a significantly reduced odds of being hospitalised with oxygen (AOR 0.43 95%CI 0.31-0.60 p<0.001). Transplanted patients were hospitalised with supplemental oxygen therapy (21.9%) more often than non-transplanted (8.8%) and was independently associated with the primary outcome (Adjusted OR 2.45 95%CI 1.27-4.71 p=0.007). Conclusions: This is the first study to show that there is a protective effect from the use of CFTR modulator therapy and that people with CF from an ethnic minority are at more risk of severe infection with SARS-CoV-2. © 2022
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  • O'Connor, M. I., et al. (författare)
  • A general biodiversity-function relationship is mediated by trophic level
  • 2017
  • Ingår i: Oikos. - : Wiley. - 0030-1299. ; 126:1, s. 18-31
  • Tidskriftsartikel (refereegranskat)abstract
    • Species diversity affects the functioning of ecosystems, including the efficiency by which communities capture limited resources, produce biomass, recycle and retain biologically essential nutrients. These ecological functions ultimately support the ecosystem services upon which humanity depends. Despite hundreds of experimental tests of the effect of biodiversity on ecosystem function (BEF), it remains unclear whether diversity effects are sufficiently general that we can use a single relationship to quantitatively predict how changes in species richness alter an ecosystem function across trophic levels, ecosystems and ecological conditions. Our objective here is to determine whether a general relationship exists between biodiversity and standing biomass. We used hierarchical mixed effects models, based on a power function between species richness and biomass production (Y = a x S-b), and a database of 374 published experiments to estimate the BEF relationship (the change in biomass with the addition of species), and its associated uncertainty, in the context of environmental factors. We found that the mean relationship (b = 0.26, 95% CI: 0.16, 0.37) characterized the vast majority of observations, was robust to differences in experimental design, and was independent of the range of species richness levels considered. However, the richness-biomass relationship varied by trophic level and among ecosystems; in aquatic systems b was nearly twice as large for consumers (herbivores and detritivores) compared to primary producers; in terrestrial ecosystems, b for detritivores was negative but depended on few studies. We estimated changes in biomass expected for a range of changes in species richness, highlighting that species loss has greater implications than species gains, skewing a distribution of biomass change relative to observed species richness change. When biomass provides a good proxy for processes that underpin ecosystem services, this relationship could be used as a step in modeling the production of ecosystem services and their dependence on biodiversity.
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  • Barack, Leor, et al. (författare)
  • Black holes, gravitational waves and fundamental physics : a roadmap
  • 2019
  • Ingår i: Classical and quantum gravity. - : IOP Publishing. - 0264-9381 .- 1361-6382. ; 36:14
  • Forskningsöversikt (refereegranskat)abstract
    • The grand challenges of contemporary fundamental physics dark matter, dark energy, vacuum energy, inflation and early universe cosmology, singularities and the hierarchy problem all involve gravity as a key component. And of all gravitational phenomena, black holes stand out in their elegant simplicity, while harbouring some of the most remarkable predictions of General Relativity: event horizons, singularities and ergoregions. The hitherto invisible landscape of the gravitational Universe is being unveiled before our eyes: the historical direct detection of gravitational waves by the LIGO-Virgo collaboration marks the dawn of a new era of scientific exploration. Gravitational-wave astronomy will allow us to test models of black hole formation, growth and evolution, as well as models of gravitational-wave generation and propagation. It will provide evidence for event horizons and ergoregions, test the theory of General Relativity itself, and may reveal the existence of new fundamental fields. The synthesis of these results has the potential to radically reshape our understanding of the cosmos and of the laws of Nature. The purpose of this work is to present a concise, yet comprehensive overview of the state of the art in the relevant fields of research, summarize important open problems, and lay out a roadmap for future progress. This write-up is an initiative taken within the framework of the European Action on 'Black holes, Gravitational waves and Fundamental Physics'.
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  • Chajes, Veronique, et al. (författare)
  • Ecological-Level Associations Between Highly Processed Food Intakes and Plasma Phospholipid Elaidic Acid Concentrations: Results From a Cross-Sectional Study Within the European Prospective Investigation Into Cancer and Nutrition (EPIC)
  • 2011
  • Ingår i: Nutrition and Cancer. - : Informa UK Limited. - 1532-7914 .- 0163-5581. ; 63:8, s. 1235-1250
  • Tidskriftsartikel (refereegranskat)abstract
    • Elaidic acid is the main unnatural trans fatty acid isomer occurring during partial hydrogenation of vegetable oils used as ingredients for the formulation of processed foods. The main objective is to assess associations between processed food intakes and plasma phospholipid elaidic acid concentrations within the European Prospective Investigation into Cancer and Nutrition study. A cross-sectional study was used to determine fatty acid profiles in 3,003 subjects from 16 centers. Single 24-h dietary recalls (24-HDR) were collected using a standardized computerized interview program. Food intakes were computed according to their degree of processing (moderately/nonprocessed foods, processed staple foods, highly processed foods). Adjusted ecological and individual correlations were calculated between processed food intakes and plasma elaidic acid levels. At the population level, mean intakes of highly processed foods were strongly correlated with mean levels of plasma elaidic acid in men (P = 0.0016) and in women (P = 0.0012). At the individual level, these associations remained but at a much lower level in men (r = 0.08, P = 0.006) and in women (r = 0.09, P = 0.0001). The use of an averaged 24-HDR measure of highly processed food intakes is adequate for predicting mean levels of plasma elaidic acid among European populations.
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  • Hooper, D. U., et al. (författare)
  • A global synthesis reveals biodiversity loss as a major driver of ecosystem change
  • 2012
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 486:7401, s. 105-
  • Tidskriftsartikel (refereegranskat)abstract
    • Evidence is mounting that extinctions are altering key processes important to the productivity and sustainability of Earth's ecosystems(1-4). Further species loss will accelerate change in ecosystem processes(5-8), but it is unclear how these effects compare to the direct effects of other forms of environmental change that are both driving diversity loss and altering ecosystem function. Here we use a suite of meta-analyses of published data to show that the effects of species loss on productivity and decomposition-two processes important in all ecosystems-are of comparable magnitude to the effects of many other global environmental changes. In experiments, intermediate levels of species loss (21-40%) reduced plant production by 5-10%, comparable to previously documented effects of ultraviolet radiation and climate warming. Higher levels of extinction (41-60%) had effects rivalling those of ozone, acidification, elevated CO2 and nutrient pollution. At intermediate levels, species loss generally had equal or greater effects on decomposition than did elevated CO2 and nitrogen addition. The identity of species lost also had a large effect on changes in productivity and decomposition, generating a wide range of plausible outcomes for extinction. Despite the need for more studies on interactive effects of diversity loss and environmental changes, our analyses clearly show that the ecosystem consequences of local species loss are as quantitatively significant as the direct effects of several global change stressors that have mobilized major international concern and remediation efforts(9).
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  • Hörnell, Agneta, et al. (författare)
  • Perspective: An extension of the STROBE statement for observational studies in nutritional epidemiology (STROBE-nut): Explanation and elaboration
  • 2017
  • Ingår i: Advances in Nutrition. - : Elsevier BV. - 2161-8313 .- 2156-5376. ; 8, s. 652-678
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2017 American Society for Nutrition. Nutritional epidemiology is an inherently complex and multifaceted research area. Dietary intake is a complex exposure and is challenging to describe and assess, and links between diet, health, and disease are difficult to ascertain. Consequently, adequate reporting is necessary to facilitate comprehension, interpretation, and generalizability of results and conclusions. The STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) statement is an international and collaborative initiative aiming to enhance the quality of reporting of observational studies. We previously presented a checklist of 24 reporting recommendations for the field of nutritional epidemiology, called "the STROBE-nut." The STROBE-nut is an extension of the general STROBE statement, intended to complement the STROBE recommendations to improve and standardize the reporting in nutritional epidemiology. The aim of the present article is to explain the rationale for, and elaborate on, the STROBE-nut recommendations to enhance the clarity and to facilitate the understanding of the guidelines. Examples from the published literature are used as illustrations, and references are provided for further reading.
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  • McKay, James D., et al. (författare)
  • A Genome-Wide Association Study of Upper Aerodigestive Tract Cancers Conducted within the INHANCE Consortium
  • 2011
  • Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 7:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p <= 5 x 10(-7)). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1 x 10(-8)) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p = 2 x 10(-8)) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5 x 10(-8); rs1229984-ADH1B, p = 7 x 10(-9); and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.
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  • Saadatian-Elahi, Mitra, et al. (författare)
  • Plasma phospholipid fatty acid profiles and their association with food intakes: results from a cross-sectional study within the European Prospective Investigation into Cancer and Nutrition
  • 2009
  • Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 1938-3207 .- 0002-9165. ; 89:1, s. 331-346
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Plasma phospholipid fatty acids have been correlated with food intakes in populations with homogeneous dietary patterns. However, few data are available on populations with heterogeneous dietary patterns. Objective: The objective was to investigate whether plasma phospholipid fatty acids are suitable biomarkers of dietary intakes across populations involved in a large European multicenter study. Design: A cross-sectional study design nested to the European Prospective Investigation into Cancer and Nutrition (EPIC) was conducted to determine plasma fatty acid profiles in > 3000 subjects from 16 centers, who had also completed 24-h dietary recalls and dietary questionnaires. Plasma fatty acids were assessed by capillary gas chromatography. Ecological and individual correlations were calculated between fatty acids and select food groups. Results: The most important determinant of plasma fatty acids was region, which suggests that the variations across regions are largely due to different food intakes. Strong ecological correlations were observed between fish intake and long-chain n-3 polyunsaturated fatty acids (r = 0.78, P < 0.01), olive oil and oleic acid (r = 0.73, P < 0.01), and margarine and elaidic acid (r = 0.76, P < 0.01). Individual correlations varied across the regions, particularly between olive oil and oleic acid and between alcohol and the saturation index, as an indicator of stearoyl CoA desaturase activity. Conclusions: These findings indicate that specific plasma phospholipid fatty acids are suitable biomarkers of some food intakes in the EPIC Study. Moreover, these findings suggest complex interactions between alcohol intake and fatty acid metabolism, which warrants further attention in epidemiologic studies relating dietary fatty acids to alcohol-related cancers and other chronic diseases. Am J Clin Nutr 2009; 89: 331-46.
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  • Zamora-Ros, Raul, et al. (författare)
  • Coffee and tea drinking in relation to the risk of differentiated thyroid carcinoma : results from the European Prospective Investigation into Cancer and Nutrition (EPIC) study
  • 2019
  • Ingår i: European Journal of Nutrition. - : Springer Berlin/Heidelberg. - 1436-6207 .- 1436-6215. ; 58:8, s. 3303-3312
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Coffee and tea constituents have shown several anti-carcinogenic activities in cellular and animal studies, including against thyroid cancer (TC). However, epidemiological evidence is still limited and inconsistent. Therefore, we aimed to investigate this association in a large prospective study.Methods: The study was conducted in the EPIC (European Prospective Investigation into Cancer and Nutrition) cohort, which included 476,108 adult men and women. Coffee and tea intakes were assessed through validated country-specific dietary questionnaires.Results: During a mean follow-up of 14 years, 748 first incident differentiated TC cases (including 601 papillary and 109 follicular TC) were identified. Coffee consumption (per 100 mL/day) was not associated either with total differentiated TC risk (HRcalibrated 1.00, 95% CI 0.97–1.04) or with the risk of TC subtypes. Tea consumption (per 100 mL/day) was not associated with the risk of total differentiated TC (HRcalibrated 0.98, 95% CI 0.95–1.02) and papillary tumor (HRcalibrated 0.99, 95% CI 0.95–1.03), whereas an inverse association was found with follicular tumor risk (HRcalibrated 0.90, 95% CI 0.81–0.99), but this association was based on a sub-analysis with a small number of cancer cases.Conclusions: In this large prospective study, coffee and tea consumptions were not associated with TC risk.
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  • Zamora-Ros, Raul, et al. (författare)
  • Energy and macronutrient intake and risk of differentiated thyroid carcinoma in the European Prospective Investigation into Cancer and Nutrition study
  • 2016
  • Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 138:1, s. 65-73
  • Tidskriftsartikel (refereegranskat)abstract
    • Incidence rates of differentiated thyroid carcinoma (TC) have increased in many countries. Adiposity and dietary risk factors may play a role, but little is known on the influence of energy intake and macronutrient composition. The aim of this study was to investigate the associations between TC and the intake of energy, macronutrients, glycemic index (GI) and glycemic load in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The study included 477,274 middle-age participants (70.2% women) from ten European countries. Dietary data were collected using country-specific validated dietary questionnaires. Total carbohydrates, proteins, fats, saturated, monounsaturated and polyunsaturated fats (PUFA), starch, sugar, and fiber were computed as g/1,000 kcal. Multivariable Cox regression was used to calculate multivariable adjusted hazard ratios (HR) and 95% confidence interval (CI) by intake quartile (Q). After a mean follow-up time of 11 years, differentiated TC was diagnosed in 556 participants (90% women). Overall, we found significant associations only with total energy (HRQ4vs.Q1, 1.29; 95% CI, 1.00-1.68) and PUFA intakes (HRQ4vs.Q1, 0.74; 95% CI, 0.57-0.95). However, the associations with starch and sugar intake and GI were significantly heterogeneous across body mass index (BMI) groups, i.e., positive associations with starch and GI were found in participants with a BMI25 and with sugar intake in those with BMI<25. Moreover, inverse associations with starch and GI were observed in subjects with BMI<25. In conclusion, our results suggest that high total energy and low PUFA intakes may increase the risk of differentiated TC. Positive associations with starch intake and GI in participants with BMI25 suggest that those persons may have a greater insulin response to high starch intake and GI than lean people. What's New? The role of lifestyle factors in the growing numbers of thyroid cancer remains unclear. Here, the authors uncover associations with high total energy intake and low consumption of polyunsaturated fatty acids in a large European cohort (EPIC). They further find positive associations with starch intake and glycemic index only in people with a body mass index equal or larger than 25, possibly implicating an altered insulin response in the etiology of this cancer.
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  • Byrnes, Andrea, et al. (författare)
  • Gene expression in peripheral blood leukocytes in monozygotic twins discordant for chronic fatigue : no evidence of a biomarker
  • 2009
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 4:6, s. e5805-
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Chronic fatiguing illness remains a poorly understood syndrome of unknown pathogenesis. We attempted to identify biomarkers for chronic fatiguing illness using microarrays to query the transcriptome in peripheral blood leukocytes. METHODS: Cases were 44 individuals who were clinically evaluated and found to meet standard international criteria for chronic fatigue syndrome or idiopathic chronic fatigue, and controls were their monozygotic co-twins who were clinically evaluated and never had even one month of impairing fatigue. Biological sampling conditions were standardized and RNA stabilizing media were used. These methodological features provide rigorous control for bias resulting from case-control mismatched ancestry and experimental error. Individual gene expression profiles were assessed using Affymetrix Human Genome U133 Plus 2.0 arrays. FINDINGS: There were no significant differences in gene expression for any transcript. CONCLUSIONS: Contrary to our expectations, we were unable to identify a biomarker for chronic fatiguing illness in the transcriptome of peripheral blood leukocytes suggesting that positive findings in prior studies may have resulted from experimental bias.
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30.
  • Byrnes, Christopher, et al. (författare)
  • Generalized interpolation in H-infinity with a complexity constraint
  • 2006
  • Ingår i: Transactions of the American Mathematical Society. - 0002-9947 .- 1088-6850. ; 358:3, s. 965-987
  • Tidskriftsartikel (refereegranskat)abstract
    • In a seminal paper, Sarason generalized some classical interpolation problems for H-infinity functions on the unit disc to problems concerning lifting onto H-2 of an operator T that is defined on K=H-2 circle minus phi H-2 (phi is an inner function) and commutes with the (compressed) shift S. In particular, he showed that interpolants (i.e., f is an element of H-infinity such that f(S)=T) having norm equal to parallel to T parallel to exist, and that in certain cases such an f is unique and can be expressed as a fraction f=b/a with a, b is an element of K. In this paper, we study interpolants that are such fractions of K functions and are bounded in norm by 1 (assuming that parallel to T parallel to<1, in which case they always exist). We parameterize the collection of all such pairs (a, b)is an element of K x K and show that each interpolant of this type can be determined as the unique minimum of a convex functional. Our motivation stems from the relevance of classical interpolation to circuit theory, systems theory, and signal processing, where phi is typically a finite Blaschke product, and where the quotient representation is a physically meaningful complexity constraint.
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31.
  • Byrnes, J. E. K., et al. (författare)
  • Investigating the relationship between biodiversity and ecosystem multifunctionality: Challenges and solutions
  • 2014
  • Ingår i: Methods in Ecology and Evolution. - 2041-210X. ; 5:2, s. 111-124
  • Tidskriftsartikel (refereegranskat)abstract
    • Summary: Extensive research shows that more species-rich assemblages are generally more productive and efficient in resource use than comparable assemblages with fewer species. But the question of how diversity simultaneously affects the wide variety of ecological functions that ecosystems perform remains relatively understudied. It presents several analytical and empirical challenges that remain unresolved. In particular, researchers have developed several disparate metrics to quantify multifunctionality, each characterizing different aspects of the concept and each with pros and cons. We compare four approaches to characterizing multifunctionality and its dependence on biodiversity, quantifying (i) magnitudes of multiple individual functions separately, (ii) the extent to which different species promote different functions, (iii) the average level of a suite of functions and (iv) the number of functions that simultaneously exceeds a critical threshold. We illustrate each approach using data from the pan-European BIODEPTH experiment and the R multifunc package developed for this purpose, evaluate the strengths and weaknesses of each approach and implement several methodological improvements. We conclude that an extension of the fourth approach that systematically explores all possible threshold values provides the most comprehensive description of multifunctionality to date. We outline this method and recommend its use in future research. © 2013 British Ecological Society.
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32.
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33.
  • Delahaye-Sourdeix, Manon, et al. (författare)
  • The 12p13.33/RAD52 locus and genetic susceptibility to squamous cell cancers of upper aerodigestive tract
  • 2015
  • Ingår i: PLOS ONE. - : Public library science. - 1932-6203. ; 10:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Genetic variants located within the 12p13.33/RAD52 locus have been associated with lung squamous cell carcinoma (LUSC). Here, within 5,947 UADT cancers and 7,789 controls from 9 different studies, we found rs10849605, a common intronic variant in RAD52, to be also associated with upper aerodigestive tract (UADT) squamous cell carcinoma cases (OR = 1.09, 95% CI: 1.04-1.15, p = 6x10(-4)). We additionally identified rs10849605 as a RAD52 cis-eQTL inUADT(p = 1x10(-3)) and LUSC (p = 9x10(-4)) tumours, with the UADT/LUSC risk allele correlated with increased RAD52 expression levels. The 12p13.33 locus, encompassing rs10849605/RAD52, was identified as a significant somatic focal copy number amplification in UADT(n = 374, q-value = 0.075) and LUSC (n = 464, q-value = 0.007) tumors and correlated with higher RAD52 tumor expression levels (p = 6x10(-48) and p = 3x10(-29) in UADT and LUSC, respectively). In combination, these results implicate increased RAD52 expression in both genetic susceptibility and tumorigenesis of UADT and LUSC tumors.
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34.
  • Duffy, J. Emmett, et al. (författare)
  • Toward a Coordinated Global Observing System for Seagrasses and Marine Macroalgae
  • 2019
  • Ingår i: Frontiers in Marine Science. - : Frontiers Media S.A.. - 2296-7745. ; 6
  • Forskningsöversikt (refereegranskat)abstract
    • In coastal waters around the world, the dominant primary producers are benthic macrophytes, including seagrasses and macroalgae, that provide habitat structure and food for diverse and abundant biological communities and drive ecosystem processes. Seagrass meadows and macroalgal forests play key roles for coastal societies, contributing to fishery yields, storm protection, biogeochemical cycling and storage, and important cultural values. These socio-economically valuable services are threatened worldwide by human activities, with substantial areas of seagrass and macroalgal forests lost over the last half-century. Tracking the status and trends in marine macrophyte cover and quality is an emerging priority for ocean and coastal management, but doing so has been challenged by limited coordination across the numerous efforts to monitor macrophytes, which vary widely in goals, methodologies, scales, capacity, governance approaches, and data availability. Here, we present a consensus assessment and recommendations on the current state of and opportunities for advancing global marine macrophyte observations, integrating contributions from a community of researchers with broad geographic and disciplinary expertise. With the increasing scale of human impacts, the time is ripe to harmonize marine macrophyte observations by building on existing networks and identifying a core set of common metrics and approaches in sampling design, field measurements, governance, capacity building, and data management. We recommend a tiered observation system, with improvement of remote sensing and remote underwater imaging to expand capacity to capture broad-scale extent at intervals of several years, coordinated with strati fied in situ sampling annually to characterize the key variables of cover and taxonomic or functional group composition, and to provide ground-truth. A robust networked system of macrophyte observations will be facilitated by establishing best practices, including standard protocols, documentation, and sharing of resources at all stages of work flow, and secure archiving of open-access data. Because such a network is necessarily distributed, sustaining it depends on close engagement of local stakeholders and focusing on building and long-term maintenance of local capacity, particularly in the developing world. Realizing these recommendations will producemore effective, efficient, and responsive observing, a more accurate global picture of change in vegetated coastal systems, and stronger international capacity for sustaining observations.
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35.
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36.
  • Jenab, Mazda, et al. (författare)
  • Association between pre-diagnostic circulating vitamin D concentration and risk of colorectal cancer in European populations : a nested case-control study
  • 2010
  • Ingår i: BMJ. British Medical Journal. - : BMJ Publishing Group. - 0959-8146 .- 0959-535X. ; 340, s. b5500-
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To examine the association between pre-diagnostic circulating vitamin D concentration, dietary intake of vitamin D and calcium, and the risk of colorectal cancer in European populations. DESIGN: Nested case-control study. Setting The study was conducted within the EPIC study, a cohort of more than 520 000 participants from 10 western European countries. PARTICIPANTS: 1248 cases of incident colorectal cancer, which developed after enrolment into the cohort, were matched to 1248 controls MAIN OUTCOME MEASURES: Circulating vitamin D concentration (25-hydroxy-vitamin-D, 25-(OH)D) was measured by enzyme immunoassay. Dietary and lifestyle data were obtained from questionnaires. Incidence rate ratios and 95% confidence intervals for the risk of colorectal cancer by 25-(OH)D concentration and levels of dietary calcium and vitamin D intake were estimated from multivariate conditional logistic regression models, with adjustment for potential dietary and other confounders. RESULTS: 25-(OH)D concentration showed a strong inverse linear dose-response association with risk of colorectal cancer (P for trend <0.001). Compared with a pre-defined mid-level concentration of 25-(OH)D (50.0-75.0 nmol/l), lower levels were associated with higher colorectal cancer risk (<25.0 nmol/l: incidence rate ratio 1.32 (95% confidence interval 0.87 to 2.01); 25.0-49.9 nmol/l: 1.28 (1.05 to 1.56), and higher concentrations associated with lower risk (75.0-99.9 nmol/l: 0.88 (0.68 to 1.13); >or=100.0 nmol/l: 0.77 (0.56 to 1.06)). In analyses by quintile of 25-(OH)D concentration, patients in the highest quintile had a 40% lower risk of colorectal cancer than did those in the lowest quintile (P<0.001). Subgroup analyses showed a strong association for colon but not rectal cancer (P for heterogeneity=0.048). Greater dietary intake of calcium was associated with a lower colorectal cancer risk. Dietary vitamin D was not associated with disease risk. Findings did not vary by sex and were not altered by corrections for season or month of blood donation. CONCLUSIONS: The results of this large observational study indicate a strong inverse association between levels of pre-diagnostic 25-(OH)D concentration and risk of colorectal cancer in western European populations. Further randomised trials are needed to assess whether increases in circulating 25-(OH)D concentration can effectively decrease the risk of colorectal cancer.
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37.
  • Kreimer, Aimée R, et al. (författare)
  • Evaluation of human papillomavirus antibodies and risk of subsequent head and neck cancer
  • 2013
  • Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 31:21, s. 2708-2715
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE:Human papillomavirus type 16 (HPV16) infection is causing an increasing number of oropharyngeal cancers in the United States and Europe. The aim of our study was to investigate whether HPV antibodies are associated with head and neck cancer risk when measured in prediagnostic sera.METHODS:We identified 638 participants with incident head and neck cancers (patients; 180 oral cancers, 135 oropharynx cancers, and 247 hypopharynx/larynx cancers) and 300 patients with esophageal cancers as well as 1,599 comparable controls from within the European Prospective Investigation Into Cancer and Nutrition cohort. Prediagnostic plasma samples from patients (collected, on average, 6 years before diagnosis) and control participants were analyzed for antibodies against multiple proteins of HPV16 as well as HPV6, HPV11, HPV18, HPV31, HPV33, HPV45, and HPV52. Odds ratios (ORs) of cancer and 95% CIs were calculated, adjusting for potential confounders. All-cause mortality was evaluated among patients using Cox proportional hazards regression.RESULTS:HPV16 E6 seropositivity was present in prediagnostic samples for 34.8% of patients with oropharyngeal cancer and 0.6% of controls (OR, 274; 95% CI, 110 to 681) but was not associated with other cancer sites. The increased risk of oropharyngeal cancer among HPV16 E6 seropositive participants was independent of time between blood collection and diagnosis and was observed more than 10 years before diagnosis. The all-cause mortality ratio among patients with oropharyngeal cancer was 0.30 (95% CI, 0.13 to 0.67), for patients who were HPV16 E6 seropositive compared with seronegative.CONCLUSION:HPV16 E6 seropositivity was present more than 10 years before diagnosis of oropharyngeal cancers.
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38.
  • Larsson, C. L., et al. (författare)
  • Strengthening the Reporting of Observational Studies in Epidemiology - nutritional epidemiology (STROBE-nut) : An extension of the STROBE statement
  • 2016
  • Ingår i: Nutrition Bulletin. - : Wiley. - 1471-9827 .- 1467-3010. ; 13:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Concerns have been raised about the quality of reporting in nutritional epidemiology. Research reporting guidelines such as the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement can improve quality of reporting in observational studies. Herein, we propose recommendations for reporting nutritional epidemiology and dietary assessment research by extending the STROBE statement into Strengthening the Reporting of Observational Studies in Epidemiology - Nutritional Epidemiology (STROBE-nut). Recommendations for the reporting of nutritional epidemiology and dietary assessment research were developed following a systematic and consultative process, co-ordinated by a multidisciplinary group of 21 experts. Consensus on reporting guidelines was reached through a three-round Delphi consultation process with 53 external experts. In total, 24 recommendations for nutritional epidemiology were added to the STROBE checklist. When used appropriately, reporting guidelines for nutritional epidemiology can contribute to improve reporting of observational studies with a focus on diet and health.
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39.
  • Lefcheck, J. S., et al. (författare)
  • Biodiversity enhances ecosystem multifunctionality across trophic levels and habitats
  • 2015
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • The importance of biodiversity for the integrated functioning of ecosystems remains unclear because most evidence comes from analyses of biodiversity's effect on individual functions. Here we show that the effects of biodiversity on ecosystem function become more important as more functions are considered. We present the first systematic investigation of biodiversity's effect on ecosystem multifunctionality across multiple taxa, trophic levels and habitats using a comprehensive database of 94 manipulations of species richness. We show that species-rich communities maintained multiple functions at higher levels than depauperate ones. These effects were stronger for herbivore biodiversity than for plant biodiversity, and were remarkably consistent across aquatic and terrestrial habitats. Despite observed tradeoffs, the overall effect of biodiversity on multifunctionality grew stronger as more functions were considered. These results indicate that prior research has underestimated the importance of biodiversity for ecosystem functioning by focusing on individual functions and taxonomic groups.
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40.
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41.
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42.
  • Zamora-Ros, Raul, et al. (författare)
  • Polyphenol intake and differentiated thyroid cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort
  • 2020
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 146:7, s. 1841-1850
  • Tidskriftsartikel (refereegranskat)abstract
    • Polyphenols are bioactive compounds with several anticarcinogenic activities; however, human data regarding associations with thyroid cancer (TC) is still negligible. Our aim was to evaluate the association between intakes of total, classes and subclasses of polyphenols and risk of differentiated TC and its main subtypes, papillary and follicular, in a European population. The European Prospective Investigation into Cancer and Nutrition cohort included 476,108 men and women from 10 European countries. During a mean follow-up of 14 years, there were 748 incident differentiated TC cases, including 601 papillary and 109 follicular tumors. Polyphenol intake was estimated at baseline using validated center/country-specific dietary questionnaires and the Phenol-Explorer database. In multivariable-adjusted Cox regression models, no association between total polyphenol and the risks of overall differentiated TC (HRQ4 vs. Q1 = 0.99, 95% confidence interval [CI] 0.77–1.29), papillary (HRQ4 vs. Q1 = 1.06, 95% CI 0.80–1.41) or follicular TC (HRQ4 vs. Q1 = 1.10, 95% CI 0.55–2.22) were found. No associations were observed either for flavonoids, phenolic acids or the rest of classes and subclasses of polyphenols. After stratification by body mass index (BMI), an inverse association between the intake of polyphenols (p-trend = 0.019) and phenolic acids (p-trend = 0.007) and differentiated TC risk in subjects with BMI ≥ 25 was observed. In conclusion, our study showed no associations between dietary polyphenol intake and differentiated TC risk; although further studies are warranted to investigate the potential protective associations in overweight and obese individuals.
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43.
  • Zamora-Ros, Raul, et al. (författare)
  • Reproductive and menstrual factors and risk of differentiated thyroid carcinoma: The EPIC study
  • 2015
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 136:5, s. 1218-1227
  • Tidskriftsartikel (refereegranskat)abstract
    • Differentiated thyroid carcinoma (TC) is threefold more common in women than in men and, therefore, a role of female hormones in the etiology of differentiated TC has been suggested. We assessed these hypotheses in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Among 345,157 women (mean age 51) followed for an average of 11 years, 508 differentiated TC cases were identified. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models. No significant associations were observed between differentiated TC risk and number of pregnancies, breast feeding, menopausal status, and age at menarche and at menopause. Significant associations were found with history of infertility problems (HR 1.70; 95% CI 1.12-2.60), a recent pregnancy (HR for 5 vs. >5 years before recruitment 3.87; 95% CI 1.43-10.46), menopause type (HR for surgical vs. natural menopause: 2.16; 95% CI 1.41-3.31), oral contraceptive (OC) use at recruitment (HR: 0.48; 95% CI 0.25-0.92) and duration of OC use (HR for 9 vs. 1 year: 0.66; 95% CI: 0.50-0.89). An increased risk was also found with hormone replacement therapy use at recruitment (HR=1.30, 95% CI 1.02-1.67), but this was not significant after adjustment for type of menopause (HR=1.22, 95% CI 0.95-1.57). Overall, our findings do not support a strong role of reproductive and menstrual factors, and female hormone use in the etiology of differentiated TC. The few observed associations may be real or accounted for by increased surveillance in women who had infertility problems, recent pregnancies or underwent surgical menopause.
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44.
  • Zamora-Ros, Raul, et al. (författare)
  • Sweetened beverages are associated with a higher risk of differentiated thyroid cancer in the EPIC cohort : a dietary pattern approach
  • 2023
  • Ingår i: European Journal of Nutrition. - : Springer Science and Business Media LLC. - 1436-6207 .- 1436-6215. ; 62:1, s. 105-114
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Dietary pattern analysis has gained particular interest, because it reflects the complexity of dietary intake. The aim of this study was to explore the associations between a posteriori dietary patterns, derived using a data-driven approach, and the risk of differentiated thyroid cancer (TC) in Europe. Methods: This investigation included 450,064 adults from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Dietary intake was assessed using validated country-specific dietary questionnaires. A posteriori dietary patterns were computed using principal component analyses. Cox regression was used to calculate multivariable adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Results: After a mean follow-up time of 14 years, 712 first differentiated TCs were diagnosed. In the fully adjusted model, a dietary pattern characterized by alcohol consumption (basically beer and wine) was negatively associated with differentiated TC risk (HRQ4vs.Q1 = 0.75; 95% CI:0.60–0.94, P-trend = 0.005), while a dietary pattern rich in sweetened beverages was positively associated with differentiated TC risk (HRQ4vs.Q1 = 1.26; 95% CI:0.99–1.61; P-trend = 0.07). The remaining 8 dietary patterns were not related to differentiated TC risk. The intake of sweetened beverages was positively associated with differentiated TC risk (HR100mL/d = 1.05; 95% CI:1.00–1.11), especially with papillary TC risk (HR100mL/d = 1.07; 95% CI:1.01–1.13). Similar results were observed with sugary and artificially sweetened beverages. Conclusions: The investigation of dietary patterns detected that the consumption of sweetened beverages was associated with a higher risk of differentiated thyroid cancer. Our results are in line with the general dietary recommendations of reducing the consumption of sweetened beverages.
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