| 1. |
- Ljungberg, Johan, et al.
(författare)
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Lipoprotein(a) and the Apolipoprotein B/A1 Ratio Independently Associate With Surgery for Aortic Stenosis Only in Patients With Concomitant Coronary Artery Disease
- 2017
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Ingår i: Journal of the American Heart Association. - : John Wiley & Sons. - 2047-9980. ; 6:12
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Aortic stenosis (AS) has different clinical phenotypes, including AS with or without concomitant coronary artery disease (CAD). It is unknown whether these phenotypes share the same risk factors. In particular, lipoprotein(a) [Lp(a)] and apolipoproteins (Apo) are associated with AS, but it is unknown whether these associations differ among phenotypes. In this prospective analysis we examined the impact of Lp(a) and Apo in subgroups of patients with AS.METHODS AND RESULTS: We identified 336 patients (mean age at survey 56.7 years, 48% female) who underwent surgery for AS after a median 10.9 years (interquartile range 9.3 years), participants in 1 of 3 large population surveys. For each patient, 2 matched referents were allocated. Lp(a) and Apo were analyzed in the baseline samples. Uni- and multivariable logistic regression analyses were used to estimate risks related to a 1 (ln) standard deviation increase in Lp(a) and the ratio of Apo B to Apo A1 (Apo B/A1 ratio). High levels of Lp(a) predicted surgery for AS in 203 patients with concomitant CAD (odds ratio [95% confidence intervals]) (1.29 [1.07-1.55]), but not in 132 patients without CAD (1.04 [0.83-1.29]) in the fully adjusted model. Similarly, a high Apo B/A1 ratio predicted surgery in patients with concomitant CAD (1.43 [1.16-1.76]) but not in those without CAD (0.87 [0.69-1.10]).CONCLUSIONS: High levels of Lp(a) and a high Apo B/A1 ratio were associated with surgery for AS in patients with concomitant CAD but not in those with isolated AS. This finding may lead to a new avenue of research for targeted risk factor interventions in this population.
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| 2. |
- Ljungberg, Johan, et al.
(författare)
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Mild impairment of renal function (shrunken pore syndrome) is associated with increased risk for future surgery for aortic stenosis
- 2019
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Taylor & Francis. - 0036-5513 .- 1502-7686. ; 79:7, s. 524-530
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Tidskriftsartikel (refereegranskat)abstract
- Recently, a new approach was proposed to detect mild impairment in renal function: a reduced ratio between estimated glomerular filtration rate (eGFR) calculated by cystatin C and eGFR calculated by creatinine. We aimed to evaluate if this ratio is associated with aortic stenosis (AS) requiring surgery. We identified 336 patients that first participated in population surveys and later underwent surgery for AS (median age [interquartile range] 59.8 [10.3] years at survey and 68.3 [12.7] at surgery, 48% females). For each patient, two matched referents were allocated. Cystatin C and creatinine were determined in stored plasma. eGFR(cystatin C) and eGFR(creatinine) and their ratio were estimated. Conditional logistic regression analyses were used to estimate the risk (odds ratio (OR) with [95% confidence interval (CI)]) related to one (ln) standard deviation increase in the ratio between eGFR(cystatin C) and eGFR(creatinine). A high ratio was associated with lower risk for AS requiring surgery (OR [95% CI]) (OR 0.84 [0.73-0.97]), especially in women (0.74 [0.60-0.92] vs. 0.93 [0.76-1.13] in men). After further stratification for coronary artery disease (CAD), the association remained in women with CAD but not in women without CAD (0.60 [0.44-0.83] and 0.89 [0.65-1.23], respectively). In conclusion, a high ratio between eGFR(cystatin C) and eGFR(creatinine) was associated with lower risk for surgery for AS, especially in women. Mild impairment of renal function is thus associated with future risk for AS requiring surgery.
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| 3. |
- Ljungberg, Johan, et al.
(författare)
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Proteomic Biomarkers for Incident Aortic Stenosis Requiring Valvular Replacement
- 2018
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Ingår i: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 0009-7322 .- 1524-4539. ; 138:6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Aortic valve stenosis (AS) is the most common indication for cardiac valve surgery; untreated AS is linked to high mortality. The etiological background of AS is unknown. Previous human studies were typically based on case-control studies. Biomarkers identified in prospective studies could lead to novel mechanistic insights. Methods: Within a large population survey with blood samples obtained at baseline, 334 patients were identified who later underwent surgery for AS (median age [interquartile range], 59.9 [10.4] years at survey and 68.3 [12.7] at surgery; 48% female). For each case, 2 matched referents were allocated. Plasma was analyzed with the multiplex proximity extension assay for screening of 92 cardiovascular candidate proteins. Conditional logistic regression models were used to assess associations between each protein and AS, with correction for multiple testing. A separate set of 106 additional cases with 212 matched referents was used in a validation study. Results: Six proteins (growth differentiation factor 15, galectin-4, von Willebrand factor, interleukin 17 receptor A, transferrin receptor protein 1, and proprotein convertase subtilisin/kexin type 9) were associated with case status in the discovery cohort; odds ratios ranged from 1.25 to 1.37 per SD increase in the protein signal. Adjusting the multivariable models for classical cardiovascular risk factors at baseline yielded similar results. Subanalyses of case-referent triplets (n=133) who showed no visible coronary artery disease at the time of surgery in the index person supported associations between AS and growth differentiation factor 15 (odds ratio, 1.40; 95% confidence interval, 1.10-1.78) and galectin-4 (odds ratio, 1.27; 95% confidence interval, 1.02-1.59), but these associations were attenuated after excluding individuals who donated blood samples within 5 years before surgery. In triplets (n=201), which included index individuals with concurrent coronary artery disease at the time of surgery, all 6 proteins were robustly associated with case status in all sensitivity analyses. In the validation study, the association of all but 1 (interleukin 17 receptor A) of these proteins were replicated in patients with AS with concurrent coronary artery disease but not in patients with AS without coronary artery disease. Conclusions: We provide evidence that 5 proteins were altered years before AS surgery and that the associations seem to be driven by concurrent atherosclerotic disease.
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| 4. |
- Andersen, Vibeke, et al.
(författare)
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Fibre intake and the development of inflammatory bowel disease : A European prospective multi-centre cohort study (EPIC-IBD)
- 2018
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Ingår i: Journal of Crohn's & Colitis. - : OXFORD UNIV PRESS. - 1873-9946 .- 1876-4479. ; 12:2, s. 129-136
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: Population-based prospective cohort studies investigating fibre intake and development of inflammatory bowel disease are lacking. Our aim was to investigate the association between fibre intake and the development of Crohn's disease [CD] and ulcerative colitis [UC] in a large European population.Methods: In total, 401 326 participants, aged 20-80 years, were recruited in eight countries in Europe between 1991 and 1998. At baseline, fibre intake [total fibres, fibres from fruit, vegetables and cereals] was recorded using food frequency questionnaires. The cohort was monitored for the development of inflammatory bowel disease. Each case was matched with four controls and odds ratios [ORs] for the exposures were calculated using conditional logistic regression. Sensitivity analyses according to smoking status were computed.Results: In total, 104 and 221 participants developed incident CD and UC, respectively. For both CD and UC, there were no statistically significant associations with either quartiles, or trends across quartiles, for total fibre or any of the individual sources. The associations were not affected by adjusting for smoking and energy intake. Stratification according to smoking status showed null findings apart from an inverse association with cereal fibre and CD in non-smokers [Quartile 4 vs 1 OR = 0.12, 95% confidence interval = 0.02-0.75, p = 0.023, OR trend across quartiles = 0.50, 95% confidence interval = 0.29-0.86, p = 0.017].Conclusion: The results do not support the hypothesis that dietary fibre is involved in the aetiology of UC, although future work should investigate whether there may be a protective effect of specific types of fibre according to smoking status in CD.
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| 5. |
- Bergemalm, Daniel, 1977-, et al.
(författare)
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Markers of systemic inflammation in preclinical ulcerative colitis
- 2019
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Ingår i: United European Gastroenterology journal. - : Sage Publications. - 2050-6406 .- 2050-6414. ; 7:8_suppl, s. 111-111
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Data on the preclinical stage of ulcerative colitis (UC) are sparse. At diagnosis, UC often shows a modest increase in systemic inflammatory markers like C-reactive protein (CRP). However, a subclinical inflammation with elevated levels of CRP and interleukin-6 (IL6) in serum have been observed several years before diagnosis [1]. First-degree relatives, including healthy twin siblings, also display elevated levels of some inflammatory markers as a consequence of shared genetic and environmental risk factors [2]. It is reasonable to believe that the preclinical inflammation, reflecting early pathogenic mechanisms, ultimately leads to a diagnosis of UC.Aim and Method: We aimed to deeper examine the systemic preclinical inflammation in UC using a comprehensive set of protein markers. Cases with UC were identified at clinical follow-up of a prospectively collected population-based cohort of healthy individuals from northern Sweden. Plasma samples from cases and controls were subjected to proximity extension assay for relative quantification of 92 protein markers of inflammation. Results were validated in an inception cohort of treatment naïve, newly diagnosed patients with UC (n=101) vs. healthy controls (n=50). In addition, to examine the impact of shared genetic and environmental factors, a cohort of healthy mono- and dizygotic twin siblings of twins with UC (n=41) and matched healthy controls (n=37) were explored.Results: Pre-diagnostic plasma samples from 72 cases who later in life developed UC and 140 controls, matched for gender, age, year of health survey and area of residence, were identified (table 1). Six proteins were significantly upregulated (p<0.05) in pre-diagnostic UC compared to matched healthy controls. A receiver-operating curve based prediction model using the six protein markers combined with sex, age, smoking status and time to diagnose was set up for validation. The model discriminated newly diagnosed, treatment naïve UC cases from healthy controls (AUC=0.96; CI 0.93-0.98). An AUC of 0.73 (CI 0.62-0.84) was observed when the model was applied to healthy twin siblings vs. healthy controls and four out of six proteins were upregulated similarly as in the pre-diagnostic samples. The relative levels of the six proteins showed an intermediate upregulation in pre-diagnostic samples and samples from healthy twin siblings compared to samples at diagnosis of UC. Only one protein showed a significant correlation with time to diagnosis in the pre-diagnostic samples. Using pathway analysis, the six protein upregulations pointed towards subclinical inflammation in UC being caused by dysregulation of four immune pathways.Conclusions: This is the first comprehensive characterisation of preclinical systemic inflammation in UC. Inflammatory proteins were upregulated several years prior to diagnosis of UC and to some extent these alterations were also seen in healthy twin siblings of UC patients. Characterisation of the preclinical stage of UC could pave the way for identification of predictive biomarkers and preventive strategies.
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| 6. |
- Berggren Söderlund, Maria, et al.
(författare)
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Vitaminer och spårämnen
- 2018. - 10
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Ingår i: Laurells Klinisk kemi i praktisk medicin. - Lund : Studentlitteratur AB. - 9789144119748 ; , s. 681-703
-
Bokkapitel (refereegranskat)
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| 7. |
- Biström, Martin, et al.
(författare)
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High serum concentration of vitamin D may protect against multiple sclerosis
- 2019
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Ingår i: Multiple Sclerosis Journal, Experimental, Translational and Clinical. - : Sage Publications. - 2055-2173. ; 5:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: High 25-hydroxyvitamin D concentrations have been associated with a reduced risk of multiple sclerosis, with indications of a stronger effect among young individuals.Objective: Investigate the 25-hydroxyvitamin D association with multiple sclerosis and test if this association is age dependent.Methods: Prospectively drawn blood samples from individuals later developing relapsing-remitting multiple sclerosis and controls matched for biobank, sex, age and date of sampling, were analysed with liquid chromatography tandem mass spectrometry.Results: High levels of 25-hydroxyvitamin D (top quintile) were associated with a reduced multiple sclerosis risk (odds ratio 0.68, 95% confidence interval 0.50-0.93).Conclusion: These findings further support a role for vitamin D in MS aetiology.
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| 8. |
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| 9. |
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| 10. |
- Connolly-Andersen, Anne-Marie, et al.
(författare)
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Increased Thrombopoiesis and Platelet Activation in Hantavirus-Infected Patients
- 2015
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press. - 0022-1899 .- 1537-6613. ; 212:7, s. 1061-1069
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Tidskriftsartikel (refereegranskat)abstract
- Background. Thrombocytopenia is a common finding during viral hemorrhagic fever, which includes hemorrhagic fever with renal syndrome (HFRS). The 2 main causes for thrombocytopenia are impaired thrombopoiesis and/or increased peripheral destruction of platelets. In addition, there is an increased intravascular coagulation risk during HFRS, which could be due to platelet activation. Methods. Thrombopoiesis was determined by quantification of platelet counts, thrombopoietin, immature platelet fraction, and mean platelet volume during HFRS. The in vivo platelet activation was determined by quantification of soluble P-selectin (sP-selectin) and glycoprotein VI (sGPVI). The function of circulating platelets was determined by ex vivo stimulation followed by flow cytometry analysis of platelet surface-bound fibrinogen and P-selectin exposure. Intravascular coagulation during disease was determined by scoring for disseminated intravascular coagulation (DIC) and recording thromboembolic complications. Results. The levels of thrombopoietin, immature platelet fraction, and mean platelet volume all indicate increased thrombopoiesis during HFRS. Circulating platelets had reduced ex vivo function during disease compared to follow-up. Most interestingly, we observed significantly increased in vivo platelet activation in HFRS patients with intravascular coagulation (DIC and thromboembolic complications) as shown by sP-selectin and sGPVI levels. Conclusions. HFRS patients have increased thrombopoiesis and platelet activation, which contributes to intravascular coagulation.
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| 11. |
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| 12. |
- Karling, Pontus, et al.
(författare)
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Improved monitoring of inflammatory activity in patients with ulcerative colitis by combination of faecal tests for haemoglobin and calprotectin
- 2019
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Taylor & Francis. - 0036-5513 .- 1502-7686. ; 79:5, s. 341-346
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Tidskriftsartikel (refereegranskat)abstract
- Faecal calprotectin (FC) tests and faecal immunological tests (FIT) for haemoglobin have been used to monitor disease activity in patients with ulcerative colitis (UC) but used alone they have some limitation concerning the predictive ability. We aimed to test if an FC test used in combination with FIT could improve the predictive ability. Consecutive out-patients with UC (n = 93) who were admitted for colonoscopy completed a single faecal sample before the start of bowel preparation. A quantitative CALPRO (R) calprotectin ELISA test and a qualitative FIT (cut-off < 40 ng/mL) were analyzed. An estimated Mayo score and a score of histological inflammation was performed blinded to the result of the faecal tests. The sensitivity, specificity, negative predictive value and positive predictive value for endoscopic inflammation (Mayo score > 1) was for FIT 85%, 83%, 96%, 57% and for FC > 186 mu g/g 73%, 87%, 87%, 54%. Corresponding results for FIT*FC > 186 mu g/g (at least one test positive) were 92%, 69%, 97%, 43%. For detecting moderate/severe histological inflammation the results were for FIT 69%, 79%, 92%, 43%, for FC > 75 mu g/g 95%, 62%, 98%, 41%, and for FIT*FC > 75 mu g/g 100%, 60%, 100%, 36%. None of the markers alone or in combination were useful to predict deep remission (Mayo score = 0 and no histological inflammation). We conclude that using the combination of an FC test and FIT shows minor improvement in predictive ability for inflammatory activity and remission in patients with UC.
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| 13. |
- Lundgren, David, et al.
(författare)
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Proton pump inhibitor use is associated with elevated faecal calprotectin levels. A cross-sectional study on subjects referred for colonoscopy
- 2019
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Ingår i: Scandinavian Journal of Gastroenterology. - : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 54:2, s. 152-157
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Faecal Calprotectin (FC) is a sensitive marker for gut inflammation. However, slightly elevated FC levels are also common in subjects without inflammation. We investigated the association between FC and clinical factors including concomitant use of medical therapy in patients with a normal colonoscopy.Material and methods: Out-patients (n=1263) referred for colonoscopy, performed FC test (CALPRO) the day before the start of bowel preparation. All subjects answered questionnaires that included questions on the present and past health history, concomitant medical treatment and gastrointestinal symptoms (GSRS). A medical record chart review was performed to check for concomitant disease, cause of referral and the result of the colonoscopy including biopsies. Inclusion criteria were a normal colonoscopy. Exclusion criteria were inflammatory bowel disease, colon cancer and high-grade dysplasia.Results: Five hundred ninety subjects fulfilled the inclusion criteria and completed the study. Thirty-six per cent of the subjects had a FC >50 mu g/g. In a logistic regression analysis, age (adjusted OR: 1.051; CI: 1.032-1.071), and the use of proton pump inhibitors (adjusted OR: 3.843; CI: 2.338-6.316), non-steroid anti-inflammatory drugs (adjusted OR: 2.411; CI: 1.162-5.002) and acetylsalicylic acid (adjusted OR: 2.934; CI: 1.085-3.448) were significantly associated with an elevated FC (>50 mu g/g).Conclusions: More than one-third of the patients with a normal colonoscopy performed in clinical routine had a slightly elevated FC level. Our results emphasise the need for attention to age, the use of proton pump inhibitors, non-steroid anti-inflammatory drugs and acetylsalicylic acid in the interpretation of FC tests in clinical practice.
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| 14. |
- Lundqvist, Anette, 1963-
(författare)
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Nutritional aspects of behaviour and biology during pregnancy and postpartum
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundA well-balanced nutritious diet is important for the pregnant woman and the growing fetus, as well as for their future health. Poor nutrition results from both over-consumption of energy-rich foods which can lead to a higher weight gain than is healthy and under-nutrition of essential nutrients. Food intake is regulated in complex biological systems by many factors, where steroid hormone is one factor involved.The overall aim of this thesis is to describe dietary intake, vitamin D levels, dietary information and dietary changes, and to study the relation between allopregnanolone and weight gain during pregnancy and postpartum.Methods Study I was a qualitative study with focus group interviews with 23 pregnant women. The text was analysed with content analysis. Study II was a quantitative cross-sectional study conducted in early pregnancy (n=209) with a reference group (n=206). Self-reported dietary data from a questionnaire was analysed using descriptive comparative statistics and a cluster analysis model (Partial Least Squares modelling). Study III had a quantitative longitudinal design. Vitamin D concentrations were analysed in 184 women, collected on five occasions during pregnancy and postpartum. Descriptive comparative statistics and a linear mixed model were used. Study IV was a quantitative longitudinal study with 60 women. Concentrations of allopregnanolone were analysed in gestational week 12 and 35. Descriptive and comparative statistics as well as Spearman’s correlation (rho) were used to describe the relationship between weight gain and allopregnanolone concentrations. Results The focus group interviews showed that women wanted to know more about different foods to reduce any risk for their child but the information about foods was partly up to themselves to find out. They expressedfeelingsof insecurityand guiltif they accidentallyate something“forbidden”. The recommendationswere followedas best as possiblealong withcommon sense todeal with dietchanges. The main themes were “Finding out by oneself”, “Getting professional advice when health problems occur”, “Being uncertain” and “Being responsible with a pinch of salt”. Some differences in the dietary patterns were found among the pregnant women compared to references, with less, vegetables (47 g/day), potatoes/rice/pasta (31 g/day), meat/fish (24 g/day) and intake of alcohol and tobacco/snuff but a higher intake of supplements. Bothpregnant women and referenceshad intakes offolatethrough diet45% (pregnant) and 22% (references) lower than current recommendations(500vs400g/day). Vitamin Dintake was34% lower than the recommendationsof 10mg/day. At least a third of the participants had insufficient plasma levels below 50 nmol/L of vitamin D. Season was a strong factor influencing the longitudinal pattern. Gestational week, season, total energy intake, dietary intake of vitamin D, and multivitamin supplementation over the previous 14 days were factors related to vitamin D levels. A correlation betweenallopregnanoloneconcentrations ingestationalweek 35and weight gainin weeks12–35was seen (p = 0.016). Therewas alsoa correlation betweenthe increase inallopregnanolone(weeks12–35) andweight gain(see above) (p = 0.028). ConclusionsDietary recommendations were described as contradictory and confusing and the dietary advice felt inadequate. The women faced their diet changes and sought information on their own but would have wished for more extensive advice from the midwife. The intake of vitamins essential for pregnancy was lower than recommended, which is also confirmed by low plasma levels of vitamin D in at least one third of the pregnant women. Vitamin D levels peaked in late pregnancy. Aside from gestational week and season which were related to plasma levels, intake from foods and supplements also affected the levels. Reasons for weight gain are complex and depend on many factors. Allopregnanolone is a factor that was seen to relate to the weight gain of the studied pregnant women.
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| 15. |
- Lundqvist, Anette, 1963-, et al.
(författare)
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Vitamin D Status during Pregnancy : a Longitudinal Study in Swedish Women from Early Pregnancy to Seven Months Postpartum
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- Low vitamin D levels during pregnancy may have negative consequences for the health of both the mother and child. Cross-sectional studies in childbearing women suggest that vitamin D levels are low during pregnancy, but few studies have followed the same women during pregnancy and postpartum. The aims of this study were to longitudinally assess vitamin D status during pregnancy and postpartum and identify the factors associated with vitamin D status in pregnant women in northern Sweden. Between September 2006 and March 2009, 184 women were consecutively recruited at five antenatal primary care clinics. Blood was sampled, and dietary intake was estimated using a food frequency questionnaire with 66 food items/food aggregates and questions on the intake of vitamin supplements at gestational weeks 12, 21, and 35, as well as at 12 and 29 weeks after birth. Plasma 25(OH) vitamin D levels were analyzed using liquid chromatography tandem-mass spectrometry. At least one-third of the women had 25(OH) vitamin D levels <50 nmol/L on at least one sampling occasion. Plasma levels increased slightly over the gestation period and peaked in late pregnancy. The levels reverted to the baseline levels after birth. Multivariate analysis showed that gestational and postpartum week, season, dietary intake of vitamin D, and vitamin supplementation were significantly related to plasma levels. There was also an influence of season on the longitudinal concentration patterns. In conclusion, more than one-third of the women studied had low 25(OH) vitamin D levels, and gestational and postpartum week was related to 25(OH) vitamin D levels after adjustment for season and vitamin D intake.
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| 16. |
- Midttun, Oivind, et al.
(författare)
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Circulating concentrations of biomarkers and metabolites related to vitamin status, one-carbon and the kynurenine pathways in US, Nordic, Asian, and Australian populations
- 2017
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Ingår i: American Journal of Clinical Nutrition. - : AMER SOC NUTRITION-ASN. - 0002-9165 .- 1938-3207. ; 105:6, s. 1314-1326
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Tidskriftsartikel (refereegranskat)abstract
- Background: Circulating concentrations of biomarkers that are related to vitamin status vary by factors such as diet, fortification, and supplement use. Published biomarker concentrations have also been influenced by the variation across laboratories, which complicates a comparison of results from different studies. Objective: We robustly and comprehensively assessed differences in biomarkers that are related to vitamin status across geographic regions. Design: The trial was a cross-sectional study in which we investigated 38 biomarkers that are related to vitamin status and one-carbon and tryptophan metabolism in serum and plasma from 5314 healthy control subjects representing 20 cohorts recruited from the United States, Nordic countries, Asia, and Australia, participating in the Lung Cancer Cohort Consortium. All samples were analyzed in a centralized laboratory. Results: Circulating concentrations of riboflavin, pyridoxal 5'-phosphate, folate, vitamin B-12, all-trans retinol, 25-hydroxyvitamin D, and a-tocopherol as well as combined vitamin scores that were based on these nutrients showed that the general B-vitamin concentration was highest in the United States and that the B vitamins and lipid soluble vitamins were low in Asians. Conversely, circulating concentrations of metabolites that are inversely related to B vitamins involved in the one-carbon and kynurenine pathways were high in Asians. The high B-vitamin concentration in the United States appears to be driven mainly by multivitamin-supplement users. Conclusions: The observed differences likely reflect the variation in intake of vitamins and, in particular, the widespread multivitamin-supplement use in the United States. The results provide valuable information about the differences in biomarker concentrations in populations across continents.
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| 17. |
- Muller, D. C., et al.
(författare)
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No association between circulating concentrations of vitamin D and risk of lung cancer : an analysis in 20 prospective studies in the Lung Cancer Cohort Consortium (LC3)
- 2018
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Ingår i: Annals of Oncology. - : Oxford University Press. - 0923-7534 .- 1569-8041. ; 29:6, s. 1468-1475
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is observational evidence suggesting that high vitamin D concentrations may protect against lung cancer. To investigate this hypothesis in detail, we measured circulating vitamin D concentrations in prediagnostic blood from 20 cohorts participating in the Lung Cancer Cohort Consortium (LC3).Patients and methods: The study included 5313 lung cancer cases and 5313 controls. Blood samples for the cases were collected, on average, 5 years before lung cancer diagnosis. Controls were individually matched to the cases by cohort, sex, age, race/ethnicity, date of blood collection, and smoking status in five categories. Liquid chromatography coupled with tandem mass spectrometry was used to separately analyze 25-hydroxyvitamin D2 [25(OH)D2] and 25-hydroxyvitamin D3 [25(OH)D3] and their concentrations were combined to give an overall measure of 25(OH)D. We used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for 25(OH)D as both continuous and categorical variables.Results: Overall, no apparent association between 25(OH)D and risk of lung cancer was observed (multivariable adjusted OR for a doubling in concentration: 0.98, 95% CI: 0.91, 1.06). Similarly, we found no clear evidence of interaction by cohort, sex, age, smoking status, or histology.Conclusion: This study did not support an association between vitamin D concentrations and lung cancer risk.
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| 18. |
- Myte, Robin, et al.
(författare)
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Components of One-carbon Metabolism Other than Folate and Colorectal Cancer Risk
- 2016
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Ingår i: Epidemiology. - 1044-3983 .- 1531-5487. ; 27:6, s. 787-796
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Despite extensive study, the role of folate in colorectal cancer remains unclear. Research has therefore begun to address the role of other elements of the folate-methionine metabolic cycles. This study investigated factors other than folate involved in one-carbon metabolism, i.e., choline, betaine, dimethylglycine, sarcosine, and methionine and relevant polymorphisms, in relation to the risk of colorectal cancer in a population with low intakes and circulating levels of folate.METHODS: This was a prospective case-control study of 613 case subjects and 1,190 matched control subjects nested within the population-based Northern Sweden Health and Disease Study. We estimated odds ratios (OR) by conditional logistic regression, and marginal risk differences with weighted maximum likelihood estimation using incidence data from the study cohort.RESULTS: Higher plasma concentrations of methionine and betaine were associated with modest colorectal cancer risk reductions (OR [95% confidence interval {CI}] for highest versus lowest tertile: 0.76 [0.57, 0.99] and 0.72 [0.55, 0.94], respectively). Estimated marginal risk differences corresponded to approximately 200 fewer colorectal cancer cases per 100,000 individuals on average. We observed no clear associations between choline, dimethylglycine, or sarcosine and colorectal cancer risk. The inverse association of methionine was modified by plasma folate concentrations (OR [95% CI] for highest/lowest versus lowest/lowest tertile of plasma methionine/folate concentrations 0.39 [0.24, 0.64], Pinteraction = 0.06).CONCLUSIONS: In this population-based, nested case-control study with a long follow-up time from baseline to diagnosis (median: 8.2 years), higher plasma concentrations of methionine and betaine were associated with lower colorectal cancer risk. See Video Abstract at http://links.lww.com/EDE/B83.
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| 19. |
- Salih, Abdulkadir, et al.
(författare)
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Smoking is associated with risk for developing inflammatory bowel disease including late onset ulcerative colitis : a prospective study
- 2018
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Ingår i: Scandinavian Journal of Gastroenterology. - : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 53:2, s. 173-178
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Life style factors have been associated with inflammatory bowel disease (IBD) but there is a lack of data on the exposure of life styles factors before the onset of IBD. Our aim was to study the association between lifestyle factors and the development of IBD in a prospective setting.Materials and methods: We performed a case control study of 72 patients who later developed ulcerative colitis (UC), 26 patients who developed Crohn's disease (CD) and 427 healthy controls from the Vasterbotten intervention project matched for gender, age, year of health survey and area of residence. At recruitment, participants completed validated lifestyle questionnaires including data on alcohol intake. Information from this was used to assess the connection between lifestyle factors and later developing IBD.Results: For CD and UC, the median age at diagnosis was 53 and 52 years and median time of survey was 4 and 6 years before diagnosis, respectively. Multivariate odds ratio (OR) showed an association between never smoking and not developing IBD, including both UC and CD, OR (95% CI) 0.341 (0.136-0.853) and 0.473 (0.259-0.864), respectively. Marital status, educational level, alcohol consumption, reported physical activity and use of moist smokeless tobacco (snus) did not differ between patients and controls.Conclusions: Smoking proves to be a risk factor for both CD and UC in this prospective case-control study. No association was seen for snus users, implying a non-nicotine pathogenic mechanism from combusted tobacco.
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| 20. |
- Späth, Florentin, 1980-, et al.
(författare)
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Immune marker changes and risk of multiple myeloma : a nested case-control study using repeated prediagnostic blood samples
- 2019
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Ingår i: Haematologica. - : Ferrata Storti Foundation. - 0390-6078 .- 1592-8721. ; 104:12, s. 2456-2464
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Tidskriftsartikel (refereegranskat)abstract
- Biomarkers reliably predicting progression to multiple myeloma (MM) are lacking. Myeloma risk has been associated with low blood levels of monocyte chemotactic protein-3 (MCP-3), macrophage inflammatory protein-1 alpha (MIP-1 alpha), vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), fractalkine, and transforming growth factor-alpha (TGF-alpha). In this study, we aimed to replicate these findings and study the individual dynamics of each marker in a prospective longitudinal cohort, thereby examining their potential as markers of myeloma progression. For this purpose, we identified 65 myeloma cases and 65 matched cancer-free controls each with two donated blood samples within the Northern Sweden Health and Disease Study. The first and repeated samples from myeloma cases were donated at a median 13 and 4 years, respectively, before the myeloma was diagnosed. Known risk factors for progression were determined by protein-, and immunofixation electrophoresis, and free light chain assays. We observed lower levels of MCP-3, VEGF, FGF-2, and TGF-alpha in myeloma patients than in controls, consistent with previous data. We also observed that these markers decreased among future myeloma patients while remaining stable in controls. Decreasing trajectories were noted for TGF-alpha (P=2.5 x 10(-4)) indicating progression to MM. Investigating this, we found that low levels of TGF-alpha assessed at the time of the repeated sample were independently associated with risk of progression in a multivariable model (hazard ratio = 3.5; P=0.003). TGF-alpha can potentially improve early detection of MM.
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| 22. |
- Theofylaktopoulou, Despoina, et al.
(författare)
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Impaired functional vitamin B6 status is associated with increased risk of lung cancer
- 2018
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 142:12, s. 2425-2434
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Tidskriftsartikel (refereegranskat)abstract
- Circulating vitamin B6 levels have been found to be inversely associated with lung cancer. Most studies have focused on the B6 form pyridoxal 5'-phosphate (PLP), a direct biomarker influenced by inflammation and other factors. Using a functional B6 marker allows further investigation of the potential role of vitamin B6 status in the pathogenesis of lung cancer. We prospectively evaluated the association of the functional marker of vitamin B6 status, the 3-hydroxykynurenine:xanthurenic acid (HK:XA) ratio, with risk of lung cancer in a nested case-control study consisting of 5,364 matched case-control pairs from the Lung Cancer Cohort Consortium (LC3). We used conditional logistic regression to evaluate the association between HK:XA and lung cancer, and random effect models to combine results from different cohorts and regions. High levels of HK:XA, indicating impaired functional B6 status, were associated with an increased risk of lung cancer, the odds ratio comparing the fourth and the first quartiles (OR4th vs. 1st) was 1.25 (95% confidence interval, 1.10-1.41). Stratified analyses indicated that this association was primarily driven by cases diagnosed with squamous cell carcinoma. Notably, the risk associated with HK:XA was approximately 50% higher in groups with a high relative frequency of squamous cell carcinoma, i.e., men, former and current smokers. This risk of squamous cell carcinoma was present in both men and women regardless of smoking status.
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- Zuo, H., et al.
(författare)
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Vitamin B6 catabolism and lung cancer risk : Results from the Lung Cancer Cohort Consortium (LC3)
- 2019
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 30:3, s. 478-485
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Tidskriftsartikel (refereegranskat)abstract
- Background Increased vitamin B6 catabolism related to inflammation, as measured by the PAr index (the ratio of 4-pyridoxic acid over the sum of pyridoxal and pyridoxal-5'-phosphate), has been positively associated with lung cancer risk in two prospective European studies. However, the extent to which this association translates to more diverse populations is not known. Materials and methods For this study, we included 5323 incident lung cancer cases and 5323 controls individually matched by age, sex, and smoking status within each of 20 prospective cohorts from the Lung Cancer Cohort Consortium. Cohort-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between PAr and lung cancer risk were calculated using conditional logistic regression and pooled using random-effects models. Results PAr was positively associated with lung cancer risk in a dose-response fashion. Comparing the fourth versus first quartiles of PAr resulted in an OR of 1.38 (95% CI: 1.19-1.59) for overall lung cancer risk. The association between PAr and lung cancer risk was most prominent in former smokers (OR: 1.69, 95% CI: 1.36-2.10), men (OR: 1.60, 95% CI: 1.28-2.00), and for cancers diagnosed within 3 years of blood draw (OR: 1.73, 95% CI: 1.34-2.23). Conclusion Based on pre-diagnostic data from 20 cohorts across 4 continents, this study confirms that increased vitamin B6 catabolism related to inflammation and immune activation is associated with a higher risk of developing lung cancer. Moreover, PAr may be a pre-diagnostic marker of lung cancer rather than a causal factor.
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