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- Tsilidis, Konstantinos K., et al.
(författare)
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Genetically predicted circulating concentrations of micronutrients and risk of colorectal cancer among individuals of European descent : a Mendelian randomization study
- 2021
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Ingår i: American Journal of Clinical Nutrition. - : Oxford University Press. - 0002-9165 .- 1938-3207. ; 113:6, s. 1490-1502
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The literature on associations of circulating concentrations of minerals and vitamins with risk of colorectal cancer is limited and inconsistent. Evidence from randomized controlled trials (RCTs) to support the efficacy of dietary modification or nutrient supplementation for colorectal cancer prevention is also limited.OBJECTIVES: To complement observational and RCT findings, we investigated associations of genetically predicted concentrations of 11 micronutrients (β-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B-6, vitamin B-12, and zinc) with colorectal cancer risk using Mendelian randomization (MR). METHODS: Two-sample MR was conducted using 58,221 individuals with colorectal cancer and 67,694 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry. Inverse variance-weighted MR analyses were performed with sensitivity analyses to assess the impact of potential violations of MR assumptions.RESULTS: Nominally significant associations were noted for genetically predicted iron concentration and higher risk of colon cancer [ORs per SD (ORSD): 1.08; 95% CI: 1.00, 1.17; P value = 0.05] and similarly for proximal colon cancer, and for vitamin B-12 concentration and higher risk of colorectal cancer (ORSD: 1.12; 95% CI: 1.03, 1.21; P value = 0.01) and similarly for colon cancer. A nominally significant association was also noted for genetically predicted selenium concentration and lower risk of colon cancer (ORSD: 0.98; 95% CI: 0.96, 1.00; P value = 0.05) and similarly for distal colon cancer. These associations were robust to sensitivity analyses. Nominally significant inverse associations were observed for zinc and risk of colorectal and distal colon cancers, but sensitivity analyses could not be performed. None of these findings survived correction for multiple testing. Genetically predicted concentrations of β-carotene, calcium, copper, folate, magnesium, phosphorus, and vitamin B-6 were not associated with disease risk.CONCLUSIONS: These results suggest possible causal associations of circulating iron and vitamin B-12 (positively) and selenium (inversely) with risk of colon cancer.
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- Haycock, Philip C, et al.
(författare)
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The association between genetically elevated polyunsaturated fatty acids and risk of cancer.
- 2023
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 91
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The causal relevance of polyunsaturated fatty acids (PUFAs) for risk of site-specific cancers remains uncertain.METHODS: Using a Mendelian randomization (MR) framework, we assessed the causal relevance of PUFAs for risk of cancer in European and East Asian ancestry individuals. We defined the primary exposure as PUFA desaturase activity, proxied by rs174546 at the FADS locus. Secondary exposures were defined as omega 3 and omega 6 PUFAs that could be proxied by genetic polymorphisms outside the FADS region. Our study used summary genetic data on 10 PUFAs and 67 cancers, corresponding to 562,871 cases and 1,619,465 controls, collected by the Fatty Acids in Cancer Mendelian Randomization Collaboration. We estimated odds ratios (ORs) for cancer per standard deviation increase in genetically proxied PUFA exposures.FINDINGS: Genetically elevated PUFA desaturase activity was associated (P < 0.0007) with higher risk (OR [95% confidence interval]) of colorectal cancer (1.09 [1.07-1.11]), esophageal squamous cell carcinoma (1.16 [1.06-1.26]), lung cancer (1.06 [1.03-1.08]) and basal cell carcinoma (1.05 [1.02-1.07]). There was little evidence for associations with reproductive cancers (OR = 1.00 [95% CI: 0.99-1.01]; Pheterogeneity = 0.25), urinary system cancers (1.03 [0.99-1.06], Pheterogeneity = 0.51), nervous system cancers (0.99 [0.95-1.03], Pheterogeneity = 0.92) or blood cancers (1.01 [0.98-1.04], Pheterogeneity = 0.09). Findings for colorectal cancer and esophageal squamous cell carcinoma remained compatible with causality in sensitivity analyses for violations of assumptions. Secondary MR analyses highlighted higher omega 6 PUFAs (arachidonic acid, gamma-linolenic acid and dihomo-gamma-linolenic acid) as potential mediators. PUFA biosynthesis is known to interact with aspirin, which increases risk of bleeding and inflammatory bowel disease. In a phenome-wide MR study of non-neoplastic diseases, we found that genetic lowering of PUFA desaturase activity, mimicking a hypothetical intervention to reduce cancer risk, was associated (P < 0.0006) with increased risk of inflammatory bowel disease but not bleeding.INTERPRETATION: The PUFA biosynthesis pathway may be an intervention target for prevention of colorectal cancer and esophageal squamous cell carcinoma but with potential for increased risk of inflammatory bowel disease.
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- Taylor, Rachael M., et al.
(författare)
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Diet quality and cardiovascular outcomes : A systematic review and meta-analysis of cohort studies
- 2024
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Ingår i: Nutrition & Dietetics. - : Wiley-Blackwell Publishing Inc.. - 1446-6368 .- 1747-0080.
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Tidskriftsartikel (refereegranskat)abstract
- AimsTo evaluate relationships between diet quality and cardiovascular outcomes.MethodsSix databases were searched for studies published between January 2007 and October 2021. Eligible studies included cohort studies that assessed the relationship between a priori diet quality and cardiovascular disease mortality and morbidity in adults. The Academy of Nutrition and Dietetics Checklist was used to assess the risk of bias. Study characteristics and outcomes were extracted from eligible studies using standardised processes. Data were summarised using risk ratios for cardiovascular disease incidence and mortality with difference compared for highest versus lowest diet quality synthesised in meta-analyses using a random effects model.ResultsOf the 4780 studies identified, 159 studies (n = 6 272 676 adults) were included. Meta-analyses identified a significantly lower cardiovascular disease incidence (n = 42 studies, relative risk 0.83, 95% CI 0.82–0.84, p < 0.001) and mortality risk (n = 49 studies, relative risk 0.83, 95% CI 0.82–0.84, p < 0.001) among those with highest versus lowest diet quality. In sensitivity analyses of a high number of pooled studies (≥13 studies) the Mediterranean style diet patterns and adherence to the heart healthy diet guidelines were significantly associated with a risk reduction of 15% and 14% for cardiovascular disease incidence and 17% and 20% for cardiovascular disease mortality respectively (p < 0.05).ConclusionsHigher diet quality is associated with lower incidence and risk of mortality for cardiovascular disease however, significant study heterogeneity was identified for these relationships.
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- Duncanson, K., et al.
(författare)
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Impact of weight management nutrition interventions on dietary outcomes in children and adolescents with overweight or obesity : a systematic review with meta-analysis
- 2021
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Ingår i: Journal of human nutrition and dietetics. - : Wiley. - 0952-3871 .- 1365-277X. ; 34:1, s. 147-177
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The impact of obesity interventions on dietary intake in children and adolescents with overweight or obesity is unclear. This systematic review aimed to investigate the impact of the dietary component of weight management interventions on the change in diet in children and adolescents with overweight or obesity.METHODS: Eligible randomised controlled trials (RCTs) published between 1975 and 2020 were identified by a systematic search following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Meta-analyses of eligible study outcomes were performed using statistical software. A multilevel random effects model was used with three significant random effects fitted using restricted maximum likelihood estimation.RESULTS: This review identified 109 RCTs, including 95 that reported at least one statistically significant dietary outcome change and 14 reporting no significant dietary change. Results from the meta-analyses (n = 29 studies) indicated that, compared to control groups, intervention groups achieved significantly greater reductions in mean total energy intake at ≤6 months (-194 kcal day-1 , 95% confidence interval = -275.80 to -112.90 kcal day-1 , P < 0.001) and up to 12 months (-112 kcal day-1 95% confidence interval = -218.92 to -5.83 kcal day-1 ) P = 0.038), increases in fruit and/or vegetable intakes over 2-12 months (n = 34, range +0.6 to +1.5 servings day-1 ) and reductions in consumption of sugar-sweetened beverages (n = 28, range -0.25 to -1.5 servings day-1 ) at 4-24 months follow-up.CONCLUSIONS: Obesity interventions with a dietary component have a modest but sustained impact on reducing total energy intake and improving intakes of specific food groups in children and adolescents with overweight or obesity. High quality RCTs that are powered to detect change in diet as a primary outcome are warranted.
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- Hastoy, B., et al.
(författare)
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Electrophysiological properties of human beta-cell lines EndoC-beta H1 and -beta H2 conform with human beta-cells
- 2018
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Limited access to human islets has prompted the development of human beta cell models. The human beta cell lines EndoC-beta H1 and EndoC-beta H2 are increasingly used by the research community. However, little is known of their electrophysiological and secretory properties. Here, we monitored parameters that constitute the glucose-triggering pathway of insulin release. Both cell lines respond to glucose (6 and 20 mM) with 2- to 3-fold stimulation of insulin secretion which correlated with an elevation of [Ca2+](i), membrane depolarisation and increased action potential firing. Similar to human primary beta cells, K-ATP channel activity is low at 1mM glucose and is further reduced upon increasing glucose concentration; an effect that was mimicked by the K-ATP channel blocker tolbutamide. The upstroke of the action potentials reflects the activation of Ca2+ channels with some small contribution of TTX-sensitive Na+ channels. The repolarisation involves activation of voltage-gated Kv2.2 channels and large-conductance Ca2+-activated K+ channels. Exocytosis presented a similar kinetics to human primary beta cells. The ultrastructure of these cells shows insulin vesicles composed of an electrondense core surrounded by a thin clear halo. We conclude that the EndoC-beta H1 and -beta H2 cells share many features of primary human beta-cells and thus represent a useful experimental model.
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