| 1. |
- Abbafati, Cristiana, et al.
(författare)
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- 2020
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Merritt, Melissa A., et al.
(författare)
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Nutrient-wide association study of 57 foods/nutrients and epithelial ovarian cancer in the European Prospective Investigation into Cancer and Nutrition study and the Netherlands Cohort Study
- 2016
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 103:1, s. 161-167
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of the role of dietary factors in epithelial ovarian cancer (EOC) development have been limited, and no specific dietary factors have been consistently associated with EOC risk.Objective: We used a nutrient-wide association study approach to systematically test the association between dietary factors and invasive EOC risk while accounting for multiple hypothesis testing by using the false discovery rate and evaluated the findings in an independent cohort.Design: We assessed dietary intake amounts of 28 foods/food groups and 29 nutrients estimated by using dietary questionnaires in the EPIC (European Prospective Investigation into Cancer and Nutrition) study (n = 1095 cases). We selected 4 foods/nutrients that were statistically significantly associated with EOC risk when comparing the extreme quartiles of intake in the EPIC study (false discovery rate = 0.43) and evaluated these factors in the NLCS (Netherlands Cohort Study; n = 383 cases). Cox regression models were used to estimate HRs and 95% CIs.Results: None of the 4 dietary factors that were associated with EOC risk in the EPIC study (cholesterol, polyunsaturated and saturated fat, and bananas) were statistically significantly associated with EOC risk in the NLCS; however, in meta-analysis of the EPIC study and the NLCS, we observed a higher risk of EOC with a high than with a low intake of saturated fat (quartile 4 compared with quartile 1; overall HR: 1.21; 95% CI: 1.04, 1.41).Conclusion: In the meta-analysis of both studies, there was a higher risk of EOC with a high than with a low intake of saturated fat.
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| 3. |
- Merritt, Melissa A., et al.
(författare)
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Investigation of Dietary Factors and Endometrial Cancer Risk Using a Nutrient-wide Association Study Approach in the EPIC and Nurses' Health Study (NHS) and NHSII
- 2015
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 24:2, s. 466-471
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Tidskriftsartikel (refereegranskat)abstract
- Data on the role of dietary factors in endometrial cancer development are limited and inconsistent. We applied a "nutrient-wide association study" approach to systematically evaluate dietary risk associations for endometrial cancer while controlling for multiple hypothesis tests using the false discovery rate (FDR) and validating the results in an independent cohort. We evaluated endometrial cancer risk associations for dietary intake of 84 foods and nutrients based on dietary questionnaires in three prospective studies, the European Prospective Investigation into Cancer and Nutrition (EPIC; N = 1,303 cases) followed by validation of nine foods/nutrients (FDR <= 0.10) in the Nurses' Health Studies (NHS/NHSII; N = 1,531 cases). Cox regression models were used to estimate HRs and 95% confidence intervals (CI). In multivariate adjusted comparisons of the extreme categories of intake at baseline, coffee was inversely associated with endometrial cancer risk (EPIC, median intake 750 g/day vs. 8.6; HR, 0.81; 95% CI, 0.68-0.97, P-trend = 0.09; NHS/NHSII, median intake 1067 g/day vs. none; HR, 0.82; 95% CI, 0.70-0.96, P-trend = 0.04). Eight other dietary factors that were associated with endometrial cancer risk in the EPIC study (total fat, monounsaturated fat, carbohydrates, phosphorus, butter, yogurt, cheese, and potatoes) were not confirmed in the NHS/NHSII. Our findings suggest that coffee intake may be inversely associated with endometrial cancer risk. Further data are needed to confirm these findings and to examine the mechanisms linking coffee intake to endometrial cancer risk to develop improved prevention strategies. (C)2015 AACR.
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| 4. |
- Papadimitriou, Nikos, et al.
(författare)
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A nutrient-wide association study for risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition and the Netherlands Cohort Study
- 2020
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Ingår i: European Journal of Nutrition. - : Springer Nature. - 1436-6207 .- 1436-6215. ; 59:7, s. 2929-2937
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The evidence from the literature regarding the association of dietary factors and risk of prostate cancer is inconclusive.Methods: A nutrient-wide association study was conducted to systematically and comprehensively evaluate the associations between 92 foods or nutrients and risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC). Cox proportional hazard regression models adjusted for total energy intake, smoking status, body mass index, physical activity, diabetes and education were used to estimate hazard ratios and 95% confidence intervals for standardized dietary intakes. As in genome-wide association studies, correction for multiple comparisons was applied using the false discovery rate (FDR < 5%) method and suggested results were replicated in an independent cohort, the Netherlands Cohort Study (NLCS).Results: A total of 5916 and 3842 incident cases of prostate cancer were diagnosed during a mean follow-up of 14 and 20 years in EPIC and NLCS, respectively. None of the dietary factors was associated with the risk of total prostate cancer in EPIC (minimum FDR-corrected P, 0.37). Null associations were also observed by disease stage, grade and fatality, except for positive associations observed for intake of dry cakes/biscuits with low-grade and butter with aggressive prostate cancer, respectively, out of which the intake of dry cakes/biscuits was replicated in the NLCS.Conclusions: Our findings provide little support for an association for the majority of the 92 examined dietary factors and risk of prostate cancer. The association of dry cakes/biscuits with low-grade prostate cancer warrants further replication given the scarcity in the literature.
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| 5. |
- Ebrahimi-Fakhari, Darius, et al.
(författare)
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Defining the clinical, molecular and imaging spectrum of adaptor protein complex 4-associated hereditary spastic paraplegia
- 2020
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Ingår i: Brain. - OXFORD ENGLAND : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 143:10, s. 2929-2944
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Tidskriftsartikel (refereegranskat)abstract
- Bi-allelic loss-of-function variants in genes that encode subunits of the adaptor protein complex 4 (AP-4) lead to prototypical yet poorly understood forms of childhood-onset and complex hereditary spastic paraplegia: SPG47 (AP4B1), SPG50 (AP4M1), SPG51 (AP4E1) and SPG52 (AP4S1). Here, we report a detailed cross-sectional analysis of clinical, imaging and molecular data of 156 patients from 101 families. Enrolled patients were of diverse ethnic backgrounds and covered a wide age range (1.0-49.3 years). While the mean age at symptom onset was 0.8 +/- 0.6 years [standard deviation (SD), range 0.2-5.0], the mean age at diagnosis was 10.2 +/- 8.5 years (SD, range 0.1-46.3). We define a set of core features: early-onset developmental delay with delayed motor milestones and significant speech delay (50% non-verbal); intellectual disability in the moderate to severe range; mild hypotonia in infancy followed by spastic diplegia (mean age: 8.4 +/- 5.1 years, SD) and later tetraplegia (mean age: 16.1 +/- 9.8 years, SD); postnatal microcephaly (83%); foot deformities (69%); and epilepsy (66%) that is intractable in a subset. At last follow-up, 36% ambulated with assistance (mean age: 8.9 +/- 6.4 years, SD) and 54% were wheelchair-dependent (mean age: 13.4 +/- 9.8 years, SD). Episodes of stereotypic laughing, possibly consistent with a pseudobulbar affect, were found in 56% of patients. Key features on neuroimaging include a thin corpus callosum (90%), ventriculomegaly (65%) often with colpocephaly, and periventricular white-matter signal abnormalities (68%). Iron deposition and polymicrogyria were found in a subset of patients. AP4B1-associated SPG47 and AP4M1-associated SPG50 accounted for the majority of cases. About two-thirds of patients were born to consanguineous parents, and 82% carried homozygous variants. Over 70 unique variants were present, the majority of which are frameshift or nonsense mutations. To track disease progression across the age spectrum, we defined the relationship between disease severity as measured by several rating scales and disease duration. We found that the presence of epilepsy, which manifested before the age of 3 years in the majority of patients, was associated with worse motor outcomes. Exploring genotype-phenotype correlations, we found that disease severity and major phenotypes were equally distributed among the four subtypes, establishing that SPG47, SPG50, SPG51 and SPG52 share a common phenotype, an 'AP-4 deficiency syndrome'. By delineating the core clinical, imaging, and molecular features of AP-4-associated hereditary spastic paraplegia across the age spectrum our results will facilitate early diagnosis, enable counselling and anticipatory guidance of affected families and help define endpoints for future interventional trials.
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| 6. |
- Kodama, Keiichi, et al.
(författare)
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Ethnic Differences in the Relationship Between Insulin Sensitivity and Insulin Response A systematic review and meta-analysis
- 2013
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 36:6, s. 1789-1796
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE-Human blood glucose levels have likely evolved toward their current point of stability over hundreds of thousands of years. The robust population stability of this trait is called canalization. It has been represented by a hyperbolic function of two variables: insulin sensitivity and insulin response. Environmental changes due to global migration may have pushed some human subpopulations to different points of stability. We hypothesized that there may be ethnic differences in the optimal states in the relationship between insulin sensitivity and insulin response. RESEARCH DESIGN AND METHODS-We identified studies that measured the insulin sensitivity index (S-I) and acute insulin response to glucose (AIR(g)) in three major ethnic groups: Africans, Caucasians, and East Asians. We identified 74 study cohorts comprising 3,813 individuals (19 African cohorts, 31 Caucasian, and 24 East Asian). We calculated the hyperbolic relationship using the mean values of SI and AIRg in the healthy cohorts with normal glucose tolerance. RESULTS-We found that Caucasian subpopulations were located around the middle point of the hyperbola, while African and East Asian subpopulations are located around unstable extreme points, where a small change in one variable is associated with a large nonlinear change in the other variable. CONCLUSIONS-Our findings suggest that the genetic background of Africans and East Asians makes them more and differentially susceptible to diabetes than Caucasians. This ethnic stratification could be implicated in the different natural courses of diabetes onset.
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| 7. |
- Axfors, Cathrine, et al.
(författare)
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Published registry-based pharmacoepidemiologic associations show limited concordance with agnostic medication-wide analyses
- 2023
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Ingår i: Journal of Clinical Epidemiology. - : Elsevier BV. - 0895-4356 .- 1878-5921. ; 160, s. 33-45
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To assess how the results of published national registry-based pharmacoepidemiology studies (where select associations are of interest) compare with an agnostic medication-wide approach (where all possible drug associations are tested).Study Design and Setting: We systematically searched for publications that reported drug associations with any, breast, colon/colorectal, or prostate cancer in the Swedish Prescribed Drug Registry. Results were compared against a previously performed agnostic medication-wide study on the same registry. Protocol: https://osf.io/kqj8n.Results: Most published studies (25/32) investigated previously reported associations. 421/913 (46%) associations had statistically significant results. 134 of the 162 unique drug-cancer associations could be paired with 70 associations in the agnostic study (corresponding drug categories and cancer types). Published studies reported smaller effect sizes and absolute effect sizes than the agnostic study, and generally used more adjustments. Agnostic analyses were less likely to report statistically significant protective associations (based on a multiplicity-corrected threshold) than their paired associations in published studies (McNemar odds ratio 0.13, P = 0.0022). Among 162 published associations, 36 (22%) showed increased risk signal and 25 (15%) protective signal at P < 0.05, while for agnostic associations, 237 (11%) showed increased risk signal and 108 (5%) protective signal at a multiplicity-corrected threshold. Associations belonging to drug categories targeted by individual published studies vs. nontargeted had smaller average effect sizes; smaller P values; and more frequent risk signals.Conclusion: Published pharmacoepidemiology studies using a national registry addressed mostly previously proposed associations, were mostly “negative”, and showed only modest concordance with their respective agnostic analyses in the same registry.
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| 8. |
- Patel, Chirag J., et al.
(författare)
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Systematic assessment of pharmaceutical prescriptions in association with cancer risk : a method to conduct a population-wide medication-wide longitudinal study
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- It is a public health priority to identify the adverse and non-adverse associations between pharmaceutical medications and cancer. We search for and evaluate associations between all prescribed medications and longitudinal cancer risk in participants of the Swedish Cancer Register (N = 9,014,975). We associated 552 different medications with incident cancer risk (any, breast, colon, and prostate) during 5.5 years of follow-up (7/1/2005-12/31/2010) in two types of statistical models, time-to-event and case-crossover. After multiple hypotheses correction and replication, 141 (26%) drugs were associated with any cancer in a time-to-event analysis constraining drug exposure to 1 year before first cancer diagnosis and adjusting for history of medication use. In a case-crossover analysis, 36 drugs (7%) were associated with decreased cancer risk. 12 drugs were found in common in both analyses with concordant direction of association. We found 14, 10, 7% of all drugs associated with colon, prostate, and breast cancers in time-to-event models. We only found 1, 2%, and 0% for these cancers, respectively, in case-crossover analyses. Pharmacoepidemiologic analyses of cancer risk are sensitive to modeling choices and false-positive findings are a threat. Medication-wide analyses using different analytical models may help suggest consistent signals of increased cancer risk.
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| 9. |
- Poveda, Alaitz, et al.
(författare)
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Environment-wide association study (EWAS) on cardiometabolic traits: A systematic assessment of the association of lifestyle variables on a longitudinal setting
- 2021
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The present study aims to assess the over-time association of ∼300 lifestyle exposures with nine cardiometabolic traits with the ultimate aim of identifying exposures/exposure groups that could inform lifestyle interventions aiming at controlling cardiometabolic diseases. The analyses were undertaken in a longitudinal sample comprising >31000 adults living in northern Sweden. Linear mixed models were used to assess the average associations of lifestyle exposures and linear regression models were used to test association with 10-year change of the cardiometabolic traits. ‘Physical activity’ and ‘General Health’ were the exposure categories containing the highest number of ‘tentative signals’ in analyses assessing the average association of lifestyle variables, while ‘Tobacco use’ was the top-category for the 10-year change association analyses. Thirteen modifiable variables showed a consistent average association among the majority of cardiometabolic traits. These variables belonged to four main groups: i) Smoking, ii) Diet (secoisolariciresinol intake and brewed coffee), iii) Leisure time physical activity and iv) a group of variables more specific to the Swedish lifestyle (snuff status, hunting/fishing during leisure time and boiled coffee). Interestingly, sweet drinks, fish intake and salt content, all lifestyle exposures frequently mentioned in public health recommendations were not broadly associated with the analysed cardiometabolic traits.
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| 10. |
- Poveda, Alaitz, et al.
(författare)
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Exposome-wide ranking of modifiable risk factors for cardiometabolic disease traits
- 2022
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- The present study assessed the temporal associations of ~ 300 lifestyle exposures with nine cardiometabolic traits to identify exposures/exposure groups that might inform lifestyle interventions for the reduction of cardiometabolic disease risk. The analyses were undertaken in a longitudinal sample comprising > 31,000 adults living in northern Sweden. Linear mixed models were used to assess the average associations of lifestyle exposures and linear regression models were used to test associations with 10-year change in the cardiometabolic traits. ‘Physical activity’ and ‘General Health’ were the exposure categories containing the highest number of ‘tentative signals’ in analyses assessing the average association of lifestyle variables, while ‘Tobacco use’ was the top category for the 10-year change association analyses. Eleven modifiable variables showed a consistent average association among the majority of cardiometabolic traits. These variables belonged to the domains: (i) Smoking, (ii) Beverage (filtered coffee), (iii) physical activity, (iv) alcohol intake, and (v) specific variables related to Nordic lifestyle (hunting/fishing during leisure time and boiled coffee consumption). We used an agnostic, data-driven approach to assess a wide range of established and novel risk factors for cardiometabolic disease. Our findings highlight key variables, along with their respective effect estimates, that might be prioritised for subsequent prediction models and lifestyle interventions.
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