| 1. |
- Mishra, A., et al.
(författare)
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Stroke genetics informs drug discovery and risk prediction across ancestries
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 611, s. 115-123
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Tidskriftsartikel (refereegranskat)abstract
- Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
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| 2. |
- Delios, A., et al.
(författare)
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Examining the generalizability of research findings from archival data
- 2022
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:30
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Tidskriftsartikel (refereegranskat)abstract
- This initiative examined systematically the extent to which a large set of archival research findings generalizes across contexts. We repeated the key analyses for 29 original strategic management effects in the same context (direct reproduction) as well as in 52 novel time periods and geographies; 45% of the reproductions returned results matching the original reports together with 55% of tests in different spans of years and 40% of tests in novel geographies. Some original findings were associated with multiple new tests. Reproducibility was the best predictor of generalizability-for the findings that proved directly reproducible, 84% emerged in other available time periods and 57% emerged in other geographies. Overall, only limited empirical evidence emerged for context sensitivity. In a forecasting survey, independent scientists were able to anticipate which effects would find support in tests in new samples.
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| 3. |
- Duarte-Salles, T., et al.
(författare)
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Dairy products and risk of hepatocellular carcinoma: The European Prospective Investigation into Cancer and Nutrition
- 2014
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Ingår i: International Journal of Cancer. - : Wiley-Liss Inc.. - 0020-7136 .- 1097-0215. ; 135:7, s. 1662-1672
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Tidskriftsartikel (refereegranskat)abstract
- Intake of dairy products has been associated with risk of some cancers, but findings are often inconsistent and information on hepatocellular carcinoma (HCC) risk is limited, particularly from prospective settings. The aim of our study was to investigate the association between consumption of total and specific dairy products (milk/cheese/yogurt) and their components (calcium/vitamin D/fats/protein), with first incident HCC (Ncases = 191) in the European Prospective Investigation into Cancer and Nutrition cohort, including a nested case-control subset (Ncases = 122) with the assessment of hepatitis B virus/hepatitis C virus infections status, liver damage and circulating insulin-like growth factor (IGF)-I levels. For cohort analyses, multivariable-adjusted Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI). For nested case-control analyses, conditional logistic regression was used to calculate odds ratios and 95% CI. A total of 477,206 participants were followed-up for an average of 11 years (person-years follow-up = 5,415,385). In the cohort study, a significant positive HCC risk association was observed for total dairy products (highest vs. lowest tertile, HR = 1.66, 95% CI: 1.13-2.43; ptrend = 0.012), milk (HR = 1.51, 95% CI: 1.02-2.24; ptrend = 0.049), and cheese (HR = 1.56, 95% CI: 1.02-2.38; ptrend = 0.101), but not yogurt (HR = 0.94, 95% CI: 0.65-1.35). Dietary calcium, vitamin D, fat and protein from dairy sources were associated with increased HCC risk, whereas the same nutrients from nondairy sources showed inverse or null associations. In the nested case-control study, similar results were observed among hepatitis-free individuals. Results from this large prospective cohort study suggest that higher consumption of dairy products, particularly milk and cheese, may be associated with increased HCC risk. Validation of these findings in other populations is necessary. Potential biologic mechanisms require further exploration. What's New? Currently, the role of dairy product intake in the development of hepatocellular carcinoma (HCC) is unclear. Using detailed data from a large multi-centric prospective cohort, this study investigated the association between consumption of total and specific dairy products with first incident HCC. The study found that higher dairy product consumption, particularly milk and cheese, was associated with increased HCC risk. Dietary calcium, vitamin D, fat and protein did not explain the observed associations. However, higher circulating IGF-I levels may play a role. © 2014 UICC.
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| 4. |
- Kilpelainen, TO, et al.
(författare)
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Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity
- 2019
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Ingår i: Nature communications. - London : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 376-
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Tidskriftsartikel (refereegranskat)abstract
- Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels.
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| 5. |
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| 6. |
- Bamia, C., et al.
(författare)
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Fruit and vegetable consumption in relation to hepatocellular carcinoma in a multi-centre, European cohort study
- 2015
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 112:7, s. 1273-1282
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Tidskriftsartikel (refereegranskat)abstract
- Background:Vegetable and/or fruit intakes in association with hepatocellular carcinoma (HCC) risk have been investigated in case-control studies conducted in specific European countries and cohort studies conducted in Asia, with inconclusive results. No multi-centre European cohort has investigated the indicated associations. Methods: In 486 799 men/women from the European Prospective Investigation into Cancer and nutrition, we identified 201 HCC cases after 11 years median follow-up. We calculated adjusted hazard ratios (HRs) for HCC incidence for sex-specific quintiles and per 100 g d(-1) increments of vegetable/fruit intakes. Results: Higher vegetable intake was associated with a statistically significant, monotonic reduction of HCC risk: HR (100 g d(-1) increment): 0.83; 95% CI: 0.71-0.98. This association was consistent in sensitivity analyses with no apparent heterogeneity across strata of HCC risk factors. Fruit intake was not associated with HCC incidence: HR (100 g d(-1) increment): 1.01; 95% CI: 0.92-1.11. Conclusions: Vegetable, but not fruit, intake is associated with lower HCC risk with no evidence for heterogeneity of this association in strata of important HCC risk factors. Mechanistic studies should clarify pathways underlying this association. Given that HCC prognosis is poor and that vegetables are practically universally accessible, our results may be important, especially for those at high risk for the disease.
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| 7. |
- Crowe, F. L., et al.
(författare)
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Dietary fibre intake and ischaemic heart disease mortality : the European Prospective Investigation into Cancer and Nutrition-Heart study
- 2012
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Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 0954-3007 .- 1476-5640. ; 66:8, s. 950-956
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/OBJECTIVES: Evidence from prospective studies is consistent in showing an inverse association between dietary fibre intake and risk of ischaemic heart disease (IHD), but whether dietary fibre from various food sources differ in their effect on IHD risk is less clear. The objective of this study was to assess the associations of total and food sources of dietary fibre with IHD mortality in the European Prospective Investigation into Cancer and Nutrition-Heart study. SUBJECTS/METHODS: Participants were 306 331 men and women from eight European countries. Dietary fibre intake was assessed using centre or country-specific diet questionnaires and calibrated using a 24-h diet recall. RESULTS: After an average follow-up of 11.5 years, there were 2381 IHD deaths among participants without cardiovascular disease at baseline. The calibrated intake of dietary fibre was inversely related with IHD mortality; each 10 g/day was associated with a 15% lower risk (relative risk (RR) 0.85; 95% confidence interval (CI): 0.73-0.99, P = 0.031). There was no difference in the associations of the individual food sources of dietary fibre with the risk of IHD mortality; RR for each 5 g/day higher cereal fibre intake was 0.91 (CI: 0.82-1.01), RR for each 2.5 g/day fruit fibre intake was 0.94 (CI: 0.88-1.01) and RR for each 2.5 g/day vegetable fibre intake was 0.90 (95% CI: 0.76-1.07). CONCLUSION: A higher consumption of dietary fibre is associated with a lower risk of fatal IHD with no clear difference in the association with IHD for fibre from cereals, fruits or vegetables.
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| 8. |
- Di Angelantonio, E., et al.
(författare)
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Glycated Hemoglobin Measurement and Prediction of Cardiovascular Disease
- 2014
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Ingår i: Jama-Journal of the American Medical Association. - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 311:12, s. 1225-1233
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE The value of measuring levels of glycated hemoglobin (HbA(1c)) for the prediction of first cardiovascular events is uncertain. OBJECTIVE To determine whether adding information on HbA(1c) values to conventional cardiovascular risk factors is associated with improvement in prediction of cardiovascular disease (CVD) risk. DESIGN, SETTING, AND PARTICIPANTS Analysis of individual-participant data available from 73 prospective studies involving 294 998 participants without a known history of diabetes mellitus or CVD at the baseline assessment. MAIN OUTCOMES AND MEASURES Measures of risk discrimination for CVD outcomes (eg, C-index) and reclassification (eg, net reclassification improvement) of participants across predicted 10-year risk categories of low (<5%), intermediate (5% to <7.5%), and high (>= 7.5%) risk. RESULTS During a median follow-up of 9.9 (interquartile range, 7.6-13.2) years, 20 840 incident fatal and nonfatal CVD outcomes (13 237 coronary heart disease and 7603 stroke outcomes) were recorded. In analyses adjusted for several conventional cardiovascular risk factors, there was an approximately J-shaped association between HbA(1c) values and CVD risk. The association between HbA(1c) values and CVD risk changed only slightly after adjustment for total cholesterol and triglyceride concentrations or estimated glomerular filtration rate, but this association attenuated somewhat after adjustment for concentrations of high-density lipoprotein cholesterol and C-reactive protein. The C-index for a CVD risk prediction model containing conventional cardiovascular risk factors alone was 0.7434 (95% CI, 0.7350 to 0.7517). The addition of information on HbA(1c) was associated with a C-index change of 0.0018 (0.0003 to 0.0033) and a net reclassification improvement of 0.42 (-0.63 to 1.48) for the categories of predicted 10-year CVD risk. The improvement provided by HbA(1c) assessment in prediction of CVD risk was equal to or better than estimated improvements for measurement of fasting, random, or postload plasma glucose levels. CONCLUSIONS AND RELEVANCE In a study of individuals without known CVD or diabetes, additional assessment of HbA(1c) values in the context of CVD risk assessment provided little incremental benefit for prediction of CVD risk.
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| 9. |
- Kriit, Hedi Katre, et al.
(författare)
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Using Distributed Lag Non-Linear Models to Estimate Exposure Lag-Response Associations between Long-Term Air Pollution Exposure and Incidence of Cardiovascular Disease
- 2022
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 19:5
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Tidskriftsartikel (refereegranskat)abstract
- Long-term air pollution exposure increases the risk for cardiovascular disease, but little is known about the temporal relationships between exposure and health outcomes. This study aims to estimate the exposure-lag response between air pollution exposure and risk for ischemic heart disease (IHD) and stroke incidence by applying distributed lag non-linear models (DLNMs). Annual mean concentrations of particles with aerodynamic diameter less than 2.5 µm (PM2.5 ) and black carbon (BC) were estimated for participants in five Swedish cohorts using dispersion models. Simultaneous estimates of exposure lags 1–10 years using DLNMs were compared with separate year specific (single lag) estimates and estimates for lag 1–5-and 6–10-years using moving average exposure. The DLNM estimated no exposure lag-response between PM2.5 total, BC, and IHD. However, for PM2.5 from local sources, a 20% risk increase per 1 µg/m3 for 1-year lag was estimated. A risk increase for stroke was suggested in relation to lags 2–4-year PM2.5 and BC, and also lags 8–9-years BC. No associations were shown in single lag models. Increased risk estimates for stroke in relation to lag 1–5-and 6–10-years BC moving averages were observed. Estimates generally supported a greater contribution to increased risk from exposure windows closer in time to incident IHD and incident stroke. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
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| 10. |
- Nilsson Sommar, Johan, et al.
(författare)
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Long-term exposure to particulate air pollution and black carbon in relation to natural and cause-specific mortality: a multicohort study in Sweden
- 2021
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Ingår i: Bmj Open. - : BMJ. - 2044-6055. ; 11:9
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To estimate concentration-response relationships for particulate matter (PM) and black carbon (BC) in relation to mortality in cohorts from three Swedish cities with comparatively low pollutant levels. Setting Cohorts from Gothenburg, Stockholm and Umea, Sweden. Design High-resolution dispersion models were used to estimate annual mean concentrations of PM with aerodynamic diameter <= 10 mu m (PM10) and <= 2.5 mu m (PM2.5), and BC, at individual addresses during each year of follow-up, 1990-2011. Moving averages were calculated for the time windows 1-5 years (lag1-5) and 6-10 years (lag6-10) preceding the outcome. Cause-specific mortality data were obtained from the national cause of death registry. Cohort-specific HRs were estimated using Cox regression models and then meta-analysed including a random effect of cohort. Participants During the study period, 7 340 cases of natural mortality, 2 755 cases of cardiovascular disease (CVD) mortality and 817 cases of respiratory and lung cancer mortality were observed among in total 68 679 individuals and 689 813 person-years of follow-up. Results Both PM10 (range: 6.3-41.9 mu g/m(3)) and BC (range: 0.2-6.8 mu g/m(3)) were associated with natural mortality showing 17% (95% CI 6% to 31%) and 9% (95% CI 0% to 18%) increased risks per 10 mu g/m(3) and 1 mu g/m(3) of lag1-5 exposure, respectively. For PM2.5 (range: 4.0-22.4 mu g/m(3)), the estimated increase was 13% per 5 mu g/m(3), but less precise (95% CI -9% to 40%). Estimates for CVD mortality appeared higher for both PM10 and PM2.5. No association was observed with respiratory mortality. Conclusion The results support an effect of long-term air pollution on natural mortality and mortality in CVD with high relative risks also at low exposure levels. These findings are relevant for future decisions concerning air quality policies.
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| 11. |
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| 12. |
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| 13. |
- Aglago, Elom K., et al.
(författare)
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Dietary intake and plasma phospholipid concentrations of saturated, monounsaturated and trans fatty acids and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort
- 2021
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 149:4, s. 865-882
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Tidskriftsartikel (refereegranskat)abstract
- Epidemiologic studies examining the association between specific fatty acids and colorectal cancer (CRC) risk are inconclusive. We investigated the association between dietary estimates and plasma levels of individual and total saturated (SFA), monounsaturated (MUFA), industrial-processed trans (iTFA), and ruminant-sourced trans (rTFA) fatty acids, and CRC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). Baseline fatty acid intakes were estimated in 450 112 participants (6162 developed CRC, median follow-up = 15 years). In a nested case-control study, plasma phospholipid fatty acids were determined by gas chromatography in 433 colon cancer cases and 433 matched controls. Multivariable-adjusted hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were computed using Cox and conditional logistic regression, respectively. Dietary total SFA (highest vs lowest quintile, HRQ5vsQ1 = 0.80; 95%CI:0.69-0.92), myristic acid (HRQ5vsQ1 = 0.83, 95%CI:0.74-0.93) and palmitic acid (HRQ5vsQ1 = 0.81, 95%CI:0.70-0.93) were inversely associated with CRC risk. Plasma myristic acid was also inversely associated with colon cancer risk (highest vs lowest quartile, ORQ4vsQ1 = 0.51; 95%CI:0.32-0.83), whereas a borderline positive association was found for plasma stearic acid (ORQ4vsQ1 = 1.63; 95%CI:1.00-2.64). Dietary total MUFA was inversely associated with colon cancer (per 1-SD increment, HR1-SD = 0.92, 95%CI: 0.85-0.98), but not rectal cancer (HR1-SD = 1.04, 95%CI:0.95-1.15, Pheterogeneity = 0.027). Dietary iTFA, and particularly elaidic acid, was positively associated with rectal cancer (HR1-SD = 1.07, 95%CI:1.02-1.13). Our results suggest that total and individual saturated fatty acids and fatty acids of industrial origin may be relevant to the aetiology of CRC. Both dietary and plasma myristic acid levels were inversely associated with colon cancer risk, which warrants further investigation.
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| 14. |
- Chajes, V., et al.
(författare)
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A prospective evaluation of plasma phospholipid fatty acids and breast cancer risk in the EPIC study
- 2017
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Ingår i: Annals of Oncology. - : Oxford University Press. - 0923-7534 .- 1569-8041. ; 28:11, s. 2836-2842
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Tidskriftsartikel (refereegranskat)abstract
- Background: Intakes of specific fatty acids have been postulated to impact breast cancer risk but epidemiological data based on dietary questionnaires remain conflicting.Materials and methods: We assessed the association between plasma phospholipid fatty acids and breast cancer risk in a case–control study nested within the European Prospective Investigation into Cancer and Nutrition study. Sixty fatty acids were measured by gas chromatography in pre-diagnostic plasma phospholipids from 2982 incident breast cancer cases matched to 2982 controls. Conditional logistic regression models were used to estimate relative risk of breast cancer by fatty acid level. The false discovery rate (q values) was computed to control for multiple comparisons. Subgroup analyses were carried out by estrogen receptor (ER) and progesterone receptor expression in the tumours.Results: A high level of palmitoleic acid [odds ratio (OR) for the highest quartile compared with the lowest OR (Q4–Q1) 1.37; 95% confidence interval (CI), 1.14–1.64; P for trend = 0.0001, q value = 0.004] as well as a high desaturation index (DI16) (16:1n–7/16:0) [OR (Q4–Q1), 1.28; 95% C, 1.07–1.54; P for trend = 0.002, q value = 0.037], as biomarkers of de novo lipogenesis, were significantly associated with increased risk of breast cancer. Levels of industrial trans-fatty acids were positively associated with ER-negative tumours [OR for the highest tertile compared with the lowest (T3–T1)=2.01; 95% CI, 1.03–3.90; P for trend = 0.047], whereas no association was found for ER-positive tumours (P-heterogeneity =0.01). No significant association was found between n-3 polyunsaturated fatty acids and breast cancer risk, overall or by hormonal receptor.Conclusion: These findings suggest that increased de novo lipogenesis, acting through increased synthesis of palmitoleic acid, could be a relevant metabolic pathway for breast tumourigenesis. Dietary trans-fatty acids derived from industrial processes may specifically increase ER-negative breast cancer risk.
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| 15. |
- Dahlén Gyllencreutz, Johan, et al.
(författare)
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Diagnostic agreement and interobserver concordance with teledermoscopy referrals
- 2017
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Ingår i: Journal of the European Academy of Dermatology and Venereology. - : Wiley. - 0926-9959 .- 1468-3083. ; 31:5, s. 898-903
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundMalignant melanoma and non-melanoma skin cancers are among the fastest increasing malignancies in many countries. With the help of new tools, such as teledermoscopy referrals between primary health care and dermatology clinics, the management of these patients could be made more efficient. ObjectiveTo evaluate the diagnostic agreement and interobserver concordance achieved when assessing referrals sent through a mobile teledermoscopic referral system as compared to referrals sent via the current paper-based system without images. MethodsThe referral information from 80 teledermoscopy referrals and 77 paper referrals were evaluated by six Swedish dermatologists. They were asked to answer questions about the probable diagnosis, the priority, and a management decision. ResultsTeledermoscopy generally resulted in higher diagnostic agreement, better triaging and more malignant tumours being booked directly to surgery. The largest difference between the referral methods was seen for invasive melanomas. Referrals for benign lesions were significantly more often correctly resent to primary health care with teledermoscopy. However, referrals for cases of melanoma in situ were also incorrectly resent five times. The interobserver concordance was moderate with both methods. ConclusionBy adding clinical and dermoscopic images to referrals, the triage process for both benign and dangerous skin tumours can be improved. With teledermoscopy, patients with melanoma especially can receive treatment more swiftly.
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| 18. |
- Iregren, A, et al.
(författare)
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Effects on the nervous system in different groups of workers exposed to aluminium
- 2001
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Ingår i: Occupational and Environmental Medicine. ; 58, s. 453-60
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE - To investigate possible neurotoxic effects in groups of aluminium pot room and foundry workers, aluminium welders, and a small group of workers exposed to aluminium in the production of flake powder.METHODS - Exposure to aluminium was evaluated with aluminium concentrations in blood and urine as well as a questionnaire. The groups exposed to aluminium were compared with a group of mild steel welders. Neurotoxic effects were studied with mood and symptom questionnaires and several psychological and neurophysiological tests.RESULTS - The pot room and foundry workers showed very low aluminium uptake as their aluminium concentrations in blood and urine were close to normal, and no effects on the nervous system were detected. The group of workers exposed to flake powder had high concentrations of aluminium in blood and urine, even higher than those of the aluminium welders. However, aluminium could not be shown to affect the functioning of the nervous system in flake powder producers. Although significant effects could not be shown in the present analysis of the data on welders, the performance of the welders exposed to high concentrations of aluminium was affected according to the analyses in the original paper from this group.CONCLUSIONS - For the pot room and foundry workers no effects related to the exposure to aluminium could be found. For the group of flake powder producers exposed for a short term no effects on the nervous systems were evident despite high levels of exposure. Due to the high concentrations of aluminium in the biological samples of this group, measures to reduce the exposure to aluminium are recommended, as effects on the central nervous system might develop after protracted exposures. However, this assumption needs to be verified in further studies.
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| 19. |
- Linseisen, Jakob, et al.
(författare)
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Red blood cell fatty acids and risk of colorectal cancer in the European Prospective investigation into cancer and nutrition (EPIC)
- 2021
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 30:5, s. 874-885
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Tidskriftsartikel (refereegranskat)abstract
- Background: A growing body of evidence suggests that alterations of dietary fatty acid (FA) profiles are associated with colorectal cancer risk. However, data from large-scale epidemiologic studies using circulating FA measurements to objectively assess individual FA and FA categories are scarce.Methods: We investigate the association between red blood cell (RBC) membrane FAs and risk of colorectal cancer in a case–control study nested within a large prospective cohort. After a median follow-up of 6.4 years, 1,069 incident colorectal cancer cases were identified and matched to 1,069 controls among participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). The FA composition of RBC phospholipids (in mol%) was analyzed by gas chromatography, and their association with risk of colorectal cancer was estimated by multivariable adjusted conditional logistic regression models.Results: After correction for multiple testing, subjects with higher concentrations of RBC stearic acid were at higher risk for colorectal cancer (OR ¼ 1.23; 95% CI ¼ 1.07–1.42, per 1 mol%). Conversely, colorectal cancer incidence decreased with increasing proportions of RBC n-3 PUFA, particularly eicosapentaenoic acid (0.75; 0.62–0.92, per 1 mol%). The findings for the n-6 PUFA arachidonic acid were inconsistent.Conclusions: The positive association between prediagnostic RBC stearic acid and colorectal cancer reflects putative differences in FA intake and metabolism between cancer cases and matched controls, which deserve further investigation. The inverse relationship between EPA and colorectal cancer is in line with the repeatedly reported protective effect of fish consumption on colorectal cancer risk.Impact: These findings add to the evidence on colorectal cancer prevention.
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| 20. |
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| 21. |
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| 23. |
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| 24. |
- Weinreich, I. D., et al.
(författare)
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Scandiatransplant Exchange Program (STEP): Development and Results From an International Kidney Exchange Program
- 2023
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Ingår i: Transplantation Direct. - 2373-8731. ; 9:11
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Tidskriftsartikel (refereegranskat)abstract
- Background. Kidney transplant candidates may be incompatible with their intended living donors because of the presence of antibodies against HLA and/or ABO. To increase the possibility of finding an acceptable kidney donor for these patients, the Scandiatransplant Exchange Program (STEP) program within Scandiatransplant was launched in 2019.Methods. This is a retrospective review of our experiences from the first 4 y of the STEP program, including details about the match runs, performed transplantations, and recipient outcomes within the program.Results. During 2019-2022, 11 match runs and 4 reruns were performed. In total, 114 pairs and 6 anonymous donors participated in these match runs. Fifty-one pairs (45%) participated in 1 match run, 31 pairs (27%) participated in 2 match runs, and 32 pairs (29%) participated in >= 3 match runs. Seventy-two individuals (63%) participated because of HLA incompatibility, 19 (17%) because of ABO incompatibility, and 7 (6%) because of both HLA and ABO incompatibility. Forty percent of the patients enrolled in the program underwent transplantation. In total, 49 transplantations have so far been performed within the program, and 46 (94%) of the recipients had a functioning kidney graft at follow-up in February 2023.Results. During 2019-2022, 11 match runs and 4 reruns were performed. In total, 114 pairs and 6 anonymous donors participated in these match runs. Fifty-one pairs (45%) participated in 1 match run, 31 pairs (27%) participated in 2 match runs, and 32 pairs (29%) participated in >= 3 match runs. Seventy-two individuals (63%) participated because of HLA incompatibility, 19 (17%) because of ABO incompatibility, and 7 (6%) because of both HLA and ABO incompatibility. Forty percent of the patients enrolled in the program underwent transplantation. In total, 49 transplantations have so far been performed within the program, and 46 (94%) of the recipients had a functioning kidney graft at follow-up in February 2023.Conclusions. The STEP program offers sensitized patients an enlarged pool of living donors and a chance of a compatible international living donor, resulting in an increased number of total transplantations. Currently, STEP is one of the largest transnational kidney exchange programs and has improved the situation for patients waiting for kidney transplantation in Scandiatransplant.
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| 25. |
- Wormser, David, et al.
(författare)
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Adult height and the risk of cause-specific death and vascular morbidity in 1 million people : individual participant meta-analysis
- 2012
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Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 41:5, s. 1419-1433
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe extent to which adult height, a biomarker of the interplay of genetic endowment and early-life experiences, is related to risk of chronic diseases in adulthood is uncertain.MethodsWe calculated hazard ratios (HRs) for height, assessed in increments of 6.5 cm, using individual-participant data on 174 374 deaths or major non-fatal vascular outcomes recorded among 1 085 949 people in 121 prospective studies.ResultsFor people born between 1900 and 1960, mean adult height increased 0.5-1 cm with each successive decade of birth. After adjustment for age, sex, smoking and year of birth, HRs per 6.5 cm greater height were 0.97 (95% confidence interval: 0.96-0.99) for death from any cause, 0.94 (0.93-0.96) for death from vascular causes, 1.04 (1.03-1.06) for death from cancer and 0.92 (0.90-0.94) for death from other causes. Height was negatively associated with death from coronary disease, stroke subtypes, heart failure, stomach and oral cancers, chronic obstructive pulmonary disease, mental disorders, liver disease and external causes. In contrast, height was positively associated with death from ruptured aortic aneurysm, pulmonary embolism, melanoma and cancers of the pancreas, endocrine and nervous systems, ovary, breast, prostate, colorectum, blood and lung. HRs per 6.5 cm greater height ranged from 1.26 (1.12-1.42) for risk of melanoma death to 0.84 (0.80-0.89) for risk of death from chronic obstructive pulmonary disease. HRs were not appreciably altered after further adjustment for adiposity, blood pressure, lipids, inflammation biomarkers, diabetes mellitus, alcohol consumption or socio-economic indicators.ConclusionAdult height has directionally opposing relationships with risk of death from several different major causes of chronic diseases.
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