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1.	Sonderby, Ida E., et al. (författare) Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia 2020 Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 25:3, s. 584-602 Tidskriftsartikel (refereegranskat)abstract Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = −0.71 to −1.37; P < 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (β = −0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10−6, 1.7 × 10−9, 3.5 × 10−12 and 1.0 × 10−4, respectively). Full scale IQ was lower in both deletion and duplication carriers compared to non-carriers. This is the first brain MRI study of the impact of the 16p11.2 distal CNV, and we demonstrate a specific effect on subcortical brain structures, suggesting a neuropathological pattern underlying the neurodevelopmental syndromes.
2.	Eussen, Simone J. P. M., et al. (författare) North-south gradients in plasma concentrations of B-vitamins and other components of one-carbon metabolism in Western Europe: results from the European Prospective Investigation into Cancer and Nutrition (EPIC) Study 2013 Ingår i: British Journal of Nutrition. - 1475-2662 .- 0007-1145. ; 110:2, s. 363-374 Tidskriftsartikel (refereegranskat)abstract Different lifestyle patterns across Europe may influence plasma concentrations of B-vitamins and one-carbon metabolites and their relation to chronic disease. Comparison of published data on one-carbon metabolites in Western European regions is difficult due to differences in sampling procedures and analytical methods between studies. The present study aimed, to compare plasma concentrations of one-carbon metabolites in Western European regions with one laboratory performing all biochemical analyses. We performed the present study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort among 5446 presumptively healthy individuals. Quantile regression was used to compare sex-specific median concentrations between Northern (Denmark and Sweden), Central (France, Germany, The Netherlands and United Kingdom) and Southern (Greece, Spain and Italy) European regions. The lowest folate concentrations were observed in Northern Europe (men, 10.4 nmol/l; women, 10.7 nmol/l) and highest concentrations in Central Europe. Cobalamin concentrations were slightly higher in Northern Europe (men, 330 pmol/l; women, 352 pmol/l) compared with Central and Southern Europe, but did not show a clear north-south gradient. Vitamin B-2 concentrations were highest in Northern Europe (men, 22.2 nmol/l; women, 26.0 nmol/l) and decreased towards Southern Europe (P-trend < 0.001). Vitamin B-6 concentrations were highest in Central Europe in men (77.3 nmol/l) and highest in the North among women (70.4 nmol/l), with decreasing concentrations towards Southern Europe in women (P-trend < 0.001). In men, concentrations of serine, glycine and sarcosine increased from the north to south. In women, sarcosine increased from Northern to Southern Europe. These findings may provide relevant information for the study of regional differences of chronic disease incidence in association with lifestyle.
3.	Fanidi, Anouar, et al. (författare) Is high vitamin B12 status a cause of lung cancer? 2019 Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 145:6, s. 1499-1503 Tidskriftsartikel (refereegranskat)abstract Vitamin B supplementation can have side effects for human health, including cancer risk. We aimed to elucidate the role of vitamin B12 in lung cancer etiology via direct measurements of pre‐diagnostic circulating vitamin B12 concentrations in a nested case–control study, complemented with a Mendelian randomization (MR) approach in an independent case–control sample. We used pre‐diagnostic biomarker data from 5183 case–control pairs nested within 20 prospective cohorts, and genetic data from 29,266 cases and 56,450 controls. Exposures included directly measured circulating vitamin B12 in pre‐diagnostic blood samples from the nested case–control study, and 8 single nucleotide polymorphisms associated with vitamin B12 concentrations in the MR study. Our main outcome of interest was increased risk for lung cancer, overall and by histological subtype, per increase in circulating vitamin B12 concentrations. We found circulating vitamin B12 to be positively associated with overall lung cancer risk in a dose response fashion (odds ratio for a doubling in B12 [ORlog2B12] = 1.15, 95% confidence interval (95%CI) = 1.06–1.25). The MR analysis based on 8 genetic variants also indicated that genetically determined higher vitamin B12 concentrations were positively associated with overall lung cancer risk (OR per 150 pmol/L standard deviation increase in B12 [ORSD] = 1.08, 95%CI = 1.00–1.16). Considering the consistency of these two independent and complementary analyses, these findings support the hypothesis that high vitamin B12 status increases the risk of lung cancer.
4.	Murphy, Michelle M, et al. (författare) Longitudinal study of the effect of pregnancy on maternal and fetal cobalamin status in healthy women and their offspring. 2007 Ingår i: Journal of Nutrition. - 0022-3166 .- 1541-6100. ; 137:8, s. 1863-1867 Tidskriftsartikel (refereegranskat)abstract Compromised cobalamin status during pregnancy may put both mother and child at risk of deficiency during lactation and subsequent development. We investigated whether changes in cobalamin status during pregnancy are associated with impaired status in the mother and the cord. Plasma cobalamin, methylmalonic acid (MMA), and holotranscobalamin (holoTC) concentrations were determined in 92 women at preconception, 8, 20, and 32 wk of pregnancy, at labor, and in the cord. All variables [geometric mean percentiles 10, 90 (P(10), P(90))] were significantly reduced from preconception [cobalamin: 293 (155, 535) pmol/L; holoTC: 63 (38,98) pmol/L; MMA: 0.12 (0.09, 0.17) micromol/L] by 20 wk of pregnancy [cobalamin: 230 (123, 432) pmol/L; holoTC: 48 (34,78) pmol/L; MMA: 0.11 (0.08, 0.15) micromol/L P < 0.001]. Plasma cobalamin and holoTC remained lower throughout the remainder of pregnancy [32 wk: 198 (107, 339); labor: 224 (117, 444); P < 0.001] and [32 wk: 45 (26,82); labor: 40 (23,79); P < 0.05], respectively. By 32 wk, MMA was greater than preconception [0.14 (0.09, 0.20) micromol/L; P < 0.01]. Plasma holoTC at 32 wk and at labor was negatively correlated with cord MMA (r = -0.51, P < 0.001 and r = -0.40, P < 0.01, respectively). Women with lower holoTC at preconception had greater increases in MMA at 32 wk and at labor. Maternal MMA at 32 wk and at labor was significantly and independently associated with cord MMA only in women with lower holoTC at preconception (regression models: R(2) = 0.707, 0.682, respectively; P < 0.01). The moderate increases observed in the cobalamin biomarker, MMA, during pregnancy may indicate a functional depletion in intracellular cobalamin status.
5.	Clarke, Robert, et al. (författare) Detection of vitamin B12 deficiency in older people by measuring vitamin B12 or the active fraction of vitamin B12, holotranscobalamin. 2007 Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 53:5, s. 963-970 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Impaired vitamin B(12) function and decreased vitamin B(12) status have been associated with neurological and cognitive impairment. Current assays analyze total vitamin B(12) concentration, only a small percentage of which is metabolically active. Concentrations of this active component, carried on holotranscobalamin (holoTC), may be of greater relevance than total vitamin B(12). METHODS: We compared the utility of serum holoTC with conventional vitamin B(12) for detection of vitamin B(12) deficiency in a population-based study of older people, using increased methylmalonic acid (MMA) concentrations as a marker of metabolic vitamin B(12) deficiency in the overall population (n = 2403) and in subsets with normal (n = 1651) and abnormal (n = 752) renal function. RESULTS: Among all participants, 6% had definite (MMA >0.75 micromol/L) and 16% had probable (MMA >0.45 micromol/L) metabolic vitamin B(12) deficiency. In receiver operating characteristic curves for detection of definite vitamin B(12) deficiency, holoTC had a greater area under the curve (AUC) compared with vitamin B(12) in all participants (0.85 vs 0.76; P <0.001) and in subsets with normal (AUC: 0.87 vs 0.79; P <0.001) and abnormal (AUC: 0.85 vs 0.74; P = 0.002) renal function. Similar findings were observed for detection of moderate vitamin B(12) deficiency. Whereas the positive predictive value for both holoTC and vitamin B(12) was greater for detection of probable than definite vitamin B(12) deficiency, both tests were associated with more false-positive than true-positive test results. CONCLUSIONS: HoloTC has a modestly superior diagnostic accuracy compared with conventional vitamin B(12) for the detection of vitamin B(12) deficiency, but neither test can be recommended to screen asymptomatic populations.
6.	Eussen, Simone J P M, et al. (författare) Oral cyanocobalamin supplementation in older people with vitamin B12 deficiency : a dose-finding trial. 2005 Ingår i: Arch Intern Med. - 0003-9926. ; 165:10, s. 1167-72 Tidskriftsartikel (refereegranskat)
7.	Morkbak, Anne L, et al. (författare) Evaluation of the technical performance of novel holotranscobalamin (holoTC) assays in a multicenter European demonstration project. 2005 Ingår i: Clin Chem Lab Med. - 1434-6621. ; 43:10, s. 1058-64 Tidskriftsartikel (refereegranskat)
8.	Nilsson, Per H., 1980-, et al. (författare) Complement-dependent inflammatory response Plasmodium-derived hemozoin in malaria 2014 Ingår i: Molecular Immunology. - 0161-5890 .- 1872-9142. ; 61:2, s. 230-230 Tidskriftsartikel (refereegranskat)
9.	Riedel, Bettina M., et al. (författare) Transcobalamin polymorphism 67A-> G, but not 776C-> G, affects serum holotranscobalamin in a cohort of healthy middle-aged men and women 2011 Ingår i: Journal of Nutrition. - Bethesda, Md. : Elsevier BV. - 0022-3166 .- 1541-6100. ; 141:10, s. 1784-1790 Tidskriftsartikel (refereegranskat)abstract Two polymorphic variants in the gene coding for transcobalamin II (TCN2), TCN2 776C-> G and TCN2 67A-> G, may alter serum holotranscobalamin (holoTC), which in turn may affect cellular uptake of cobalamin (Cbl) and thereby Cbl status indicators. We studied the effects of TCN2 776C- > G and TCN2 67A- > G on blood concentrations of holoTC, Cbl, methylmalonic acid (MMA), and total homocysteine (tHcy) in 2411 individuals (50-64 y) that had been selected on the basis of these TCN2 genotypes from 10601 Norwegian inhabitants. The serum holoTC concentration was lower in TCN2 67AG (55 +/- 0.75 pmol/L) and 67GG (48 +/- 2.14 pmol/L) than in 67AA (62 +/- 0.67 pmol/L) (P < 0.001) but did not differ among TCN2 776C-> G genotypes. The polymorphisms interacted as serum holoTC determinants (P= 0.001) and the presence of TCN2 67AG and GG in strata of 776CC and CG, but not 776GG, increased the risk of having serum holoTC <45.6 pmol/L [tertile 1 vs. tertiles 2 and 3: OR = 2.5(95% CI 1.8-3.5) for 67AG; OR = 5.7 (95% Cl 3.5-9.1) for 67GG in 776CC; OR = 2.1 195% Cl 1.6-2.9) for 67AG; and OR = 4.5 (95% Cl 2.4-8.2) for 67GG in 776CG; all P < 0.0011. Plasma MMA, tHcy, and Cbl were not affected by either polymorphism. In summary, serum holoTC, but not plasma Cbl, MMA, or tHcy, varied according to TCN2 67A-> G genotypes. It remains to be determined whether this polymorphic effect on serum holoTC alters its diagnostic utility as Cbl status indicator.
10.	Theofylaktopoulou, Despoina, et al. (författare) Impaired functional vitamin B6 status is associated with increased risk of lung cancer 2018 Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 142:12, s. 2425-2434 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.
11.	Fanidi, Anouar, et al. (författare) Circulating Folate, Vitamin B6, and Methionine in Relation to Lung Cancer Risk in the Lung Cancer Cohort Consortium (LC3) 2018 Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 110:1 Tidskriftsartikel (refereegranskat)abstract Background: Circulating concentrations of B vitamins and factors related to one-carbon metabolism have been found to be strongly inversely associated with lung cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The extent to which these associations are present in other study populations is unknown.Methods: Within 20 prospective cohorts from the National Cancer Institute Cohort Consortium, a nested case-control study was designed including 5364 incident lung cancer case patients and 5364 control subjects who were individually matched to case patients by age, sex, cohort, and smoking status. Centralized biochemical analyses were performed to measure circulating concentrations of vitamin B6, folate, and methionine, as well as cotinine as an indicator of recent tobacco exposure. The association between these biomarkers and lung cancer risk was evaluated using conditional logistic regression models.Results: Participants with higher circulating concentrations of vitamin B6 and folate had a modestly decreased risk of lung cancer risk overall, the odds ratios when comparing the top and bottom fourths (OR 4vs1 ) being 0.88 (95% confidence interval [CI] = 0.78 to 1.00) and 0.86 (95% CI = 0.74 to 0.99), respectively. We found stronger associations among men (vitamin B6: OR 4vs1 = 0.74, 95% CI = 0.62 to 0.89; folate: OR 4vs1 = 0.75, 95% CI = 0.61 to 0.93) and ever smokers (vitamin B6: OR 4vs1 = 0.78, 95% CI = 0.67 to 0.91; folate: OR 4vs1 = 0.87, 95% CI = 0.73 to 1.03). We further noted that the association of folate was restricted to Europe/Australia and Asia, whereas no clear association was observed for the United States. Circulating concentrations of methionine were not associated with lung cancer risk overall or in important subgroups.Conclusions: Although confounding by tobacco exposure or reverse causation cannot be ruled out, these study results are compatible with a small decrease in lung cancer risk in ever smokers who avoid low concentrations of circulating folate and vitamin B6.
12.	Huang, Joyce Y., et al. (författare) Circulating markers of cellular immune activation in prediagnostic blood sample and lung cancer risk in the Lung Cancer Cohort Consortium (LC3) 2020 Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 146:9, s. 2394-2405 Tidskriftsartikel (refereegranskat)abstract Cell-mediated immune suppression may play an important role in lung carcinogenesis. We investigated the associations for circulating levels of tryptophan, kynurenine, kynurenine:tryptophan ratio (KTR), quinolinic acid (QA) and neopterin as markers of immune regulation and inflammation with lung cancer risk in 5,364 smoking-matched case-control pairs from 20 prospective cohorts included in the international Lung Cancer Cohort Consortium. All biomarkers were quantified by mass spectrometry-based methods in serum/plasma samples collected on average 6 years before lung cancer diagnosis. Odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer associated with individual biomarkers were calculated using conditional logistic regression with adjustment for circulating cotinine. Compared to the lowest quintile, the highest quintiles of kynurenine, KTR, QA and neopterin were associated with a 20-30% higher risk, and tryptophan with a 15% lower risk of lung cancer (all p(trend) < 0.05). The strongest associations were seen for current smokers, where the adjusted ORs (95% CIs) of lung cancer for the highest quintile of KTR, QA and neopterin were 1.42 (1.15-1.75), 1.42 (1.14-1.76) and 1.45 (1.13-1.86), respectively. A stronger association was also seen for KTR and QA with risk of lung squamous cell carcinoma followed by adenocarcinoma, and for lung cancer diagnosed within the first 2 years after blood draw. This study demonstrated that components of the tryptophan-kynurenine pathway with immunomodulatory effects are associated with risk of lung cancer overall, especially for current smokers. Further research is needed to evaluate the role of these biomarkers in lung carcinogenesis and progression.
13.	Johansson, Mattias, et al. (författare) Serum B vitamin levels and risk of lung cancer 2010 Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association. - 0098-7484 .- 1538-3598. ; 303:23, s. 2377-2385 Tidskriftsartikel (refereegranskat)abstract CONTEXT: B vitamins and factors related to 1-carbon metabolism help to maintain DNA integrity and regulate gene expression and may affect cancer risk. OBJECTIVE: To investigate if 1-carbon metabolism factors are associated with onset of lung cancer. DESIGN, SETTING, AND PARTICIPANTS: The European Prospective Investigation into Cancer and Nutrition (EPIC) recruited 519,978 participants from 10 countries between 1992 and 2000, of whom 385,747 donated blood. By 2006, 899 lung cancer cases were identified and 1770 control participants were individually matched by country, sex, date of birth, and date of blood collection. Serum levels were measured for 6 factors of 1-carbon metabolism and cotinine. MAIN OUTCOME MEASURE: Odds ratios (ORs) of lung cancer by serum levels of 4 B vitamins (B(2), B(6), folate [B(9)], and B(12)), methionine, and homocysteine. RESULTS: Within the entire EPIC cohort, the age-standardized incidence rates of lung cancer (standardized to the world population, aged 35-79 years) were 6.6, 44.9, and 156.1 per 100,000 person-years among never, former, and current smokers for men, respectively. The corresponding incidence rates for women were 7.1, 23.9, and 100.9 per 100,000 person-years, respectively. After accounting for smoking, a lower risk for lung cancer was seen for elevated serum levels of B(6) (fourth vs first quartile OR, 0.44; 95% confidence interval [CI], 0.33-0.60; P for trend <.000001), as well as for serum methionine (fourth vs first quartile OR, 0.52; 95% CI, 0.39-0.69; P for trend <.000001). Similar and consistent decreases in risk were observed in never, former, and current smokers, indicating that results were not due to confounding by smoking. The magnitude of risk was also constant with increasing length of follow-up, indicating that the associations were not explained by preclinical disease. A lower risk was also seen for serum folate (fourth vs first quartile OR, 0.68; 95% CI, 0.51-0.90; P for trend = .001), although this was apparent only for former and current smokers. When participants were classified by median levels of serum methionine and B(6), having above-median levels of both was associated with a lower lung cancer risk overall (OR, 0.41; 95% CI, 0.31-0.54), as well as separately among never (OR, 0.36; 95% CI, 0.18-0.72), former (OR, 0.51; 95% CI, 0.34-0.76), and current smokers (OR, 0.42; 95% CI, 0.27-0.65). CONCLUSION: Serum levels of vitamin B(6) and methionine were inversely associated with risk of lung cancer.
14.	Midttun, Oivind, et al. (författare) Circulating concentrations of biomarkers and metabolites related to vitamin status, one-carbon and the kynurenine pathways in US, Nordic, Asian, and Australian populations 2017 Ingår i: American Journal of Clinical Nutrition. - : AMER SOC NUTRITION-ASN. - 0002-9165 .- 1938-3207. ; 105:6, s. 1314-1326 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.
15.	Nilsen, M. S., et al. (författare) 3-Hydroxyisobutyrate, A Strong Marker of Insulin Resistance in Type 2 Diabetes and Obesity That Modulates White and Brown Adipocyte Metabolism 2020 Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 69:9, s. 1903-1916 Tidskriftsartikel (refereegranskat)abstract Circulating branched-chain amino acids (BCAAs) associate with insulin resistance and type 2 diabetes. 3-Hydroxyisobutyrate (3-HIB) is a catabolic intermediate of the BCAA valine. In this study, we show that in a cohort of 4,942 men and women, circulating 3-HIB is elevated according to levels of hyperglycemia and established type 2 diabetes. In complementary cohorts with measures of insulin resistance, we found positive correlates for circulating 3-HIB concentrations with HOMA2 of insulin resistance, as well as a transient increase in 3-HIB followed by a marked decrease after bariatric surgery and weight loss. During differentiation, both white and brown adipocytes upregulate BCAA utilization and release increasing amounts of 3-HIB. Knockdown of the 3-HIB-forming enzyme 3-hydroxyisobutyryl-CoA hydrolase decreases release of 3-HIB and lipid accumulation in both cell types. Conversely, addition of 3-HIB to white and brown adipocyte cultures increases fatty acid uptake and modulated insulin-stimulated glucose uptake in a time-dependent manner. Finally, 3-HIB treatment decreases mitochondrial oxygen consumption and generation of reactive oxygen species in white adipocytes, while increasing these measures in brown adipocytes. Our data establish 3-HIB as a novel adipocyte-derived regulator of adipocyte subtype-specific functions strongly linked to obesity, insulin resistance, and type 2 diabetes.
16.	Refsum, Helga, et al. (författare) Facts and recommendations about total homocysteine determinations : an expert opinion. 2004 Ingår i: Clin Chem. - 0009-9147. ; 50:1, s. 3-32 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
17.	Ueland, Grethe Å., et al. (författare) The Short Cosyntropin Test Revisited : New Normal Reference Range Using LC-MS/MS 2018 Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 103:4, s. 1696-1703 Tidskriftsartikel (refereegranskat)abstract Background: The cosyntropin test is used to diagnose adrenal insufficiency (AI) and nonclassical congenital adrenal hyperplasia (NCCAH). Current cutoffs for cortisol and 17-hydroxyprogesterone (17-OHP) are derived from nonstandardized immunoassays. Liquid chromatography tandem mass spectrometry (LC-MS/MS) offers direct measurement of steroids, prompting the need to re-establish normal ranges. Objective: The goal of this study was to define cutoff values for cortisol and 17-OHP in serum by LC-MS/MS 30 and 60 minutes after intravenous administration of 250 µg tetracosactide acetate to healthy volunteers and to compare the results with LC-MS/MS with routine immunoassays. Methods: Cosyntropin testing was performed in healthy subjects (n = 138) and in patients referred for evaluation of adrenocortical function (n = 94). Steroids were assayed by LC-MS/MS and compared with two immunoassays used in routine diagnostics (Immulite and Roche platforms). The cutoff level for cortisol was defined as the 2.5% percentile in healthy subjects not using oral estrogens (n = 121) and for 17-OHP as the 97.5% percentile. Results: Cortisol cutoff levels for LC-MS/MS were 412 and 485 nmol/L at 30 and 60 minutes, respectively. Applying the new cutoffs, 13 of 60 (22%) subjects who had AI according to conventional criteria now had a normal test result. For 17-OHP, the cutoff levels were 8.9 and 9.0 nmol/L at 30 and 60 minutes, respectively. Conclusions: LC-MS/MS provides cutoff levels for cortisol and 17-OHP after cosyntropin stimulation that are lower than those based on immunoassays, possibly because cross-reactivity between steroid intermediates and cortisol is eliminated. This reduces the number of false-positive tests for AI and false-negative tests for NCCAH.
18.	Aleksandrova, Krasimira, et al. (författare) A prospective study of the immune system activation biomarker neopterin and colorectal cancer risk 2015 Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 107:4 Tidskriftsartikel (refereegranskat)abstract Background: Neopterin may be relevant for colorectal cancer (CRC) development, as a biomarker of cellular immune activity exerting pleiotropic effects on cellular ageing, oxidative stress, and inflammation. So far, the association between prediagnostic neopterin and colon and rectal cancer risk has not been evaluated in human populations. Methods: A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition cohort using data on plasma concentrations of total neopterin (T-N, sum of neopterin and 7,8-dihydroneopterin) in 830 incident CRC case patients (561 colon and 269 rectal) matched within risk sets to 830 control participants. A subsequent replication study used data from the Hordaland Health Study, where 173 CRC case patients have been diagnosed among 6594 healthy participants over 12 years of follow-up. Results: After multivariable adjustment for a priori chosen CRC risk factors, a "U-shaped" association of T-N with CRC was revealed. Compared with the second quintile of the T-N distribution, the relative risks for the first, third, fourth, and fifth quintiles were 2.37 (95% CI = 1.66 to 3.39), 1.24 (95% CI = 0.87 to 1.77), 1.55 (95% CI = 1.08 to 2.22), and 2.31 (95% CI = 1.63 to 3.27), respectively. Replication of these associations within the Hordaland Health Study yielded similar results. No differences have been observed when the associations were explored by colon and rectal cancer site (two-sided P-difference = .87) and after excluding case patients diagnosed within the first four follow-up years. Conclusions: These novel findings provide evidence of the role of both suppressed and activated cell-mediated immunity as reflected by prediagnostic T-N concentrations in the development of CRC.
19.	Baltar, Valéria Troncoso, et al. (författare) Smoking, secondhand smoke, and cotinine levels in a subset of EPIC cohort 2011 Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 20:5, s. 869-875 Tidskriftsartikel (refereegranskat)abstract Background: Several countries are discussing new legislation regarding the ban on smoking in public places, based on the growing evidence of the hazards of secondhand smoke (SHS) exposure. The objective of the present study is to quantitatively assess the relationship between smoking, SHS, and serum cotinine levels in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods: From a study on lung cancer in the EPIC cohort, questionnaire information on smoking was collected at enrolment, and cotinine was measured in serum. Three statistical models were applied by using samples available in a cross-section design: (i) cotinine levels by categories combining smoking and SHS (n = 859); (ii) the effect of hours of passive smoking exposure in nonsmokers only (n = 107); (iii) the effect of the number of cigarettes consumed per day in current smokers only (n = 832). All models were adjusted for country, sex, age, and body mass index. Results: Among nonsmokers, passive smokers presented significant differences in cotinine compared with nonexposed, with a marked (but not significant) difference among former-smokers. A one hour per day increment of SHS gave rise to a significant 2.58 nmol/L (0.45 ng/mL) increase in mean serum cotinine (P < 0.001). In current smokers, a one cigarette per day increment gave rise to a significant 22.44 nmol/L (3.95 ng/mL) increase in cotinine mean (P < 0.001). Conclusions: There is clear evidence that not only tobacco smoking but also involuntary exposure increases cotinine levels. Impact: This study strengthens the evidence for the benefits of a smoking ban in public places.
20.	Chandyo, Ram K., et al. (författare) Nutritional Intake and Status of Cobalamin and Folate among Non-Pregnant Women of Reproductive Age in Bhaktapur, Nepal 2016 Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 8:6 Tidskriftsartikel (refereegranskat)abstract Cobalamin and folate are especially important for women of childbearing age due to their ubiquitous role in fetal growth and development. Population-based data on cobalamin and folate status are lacking from Nepal, where diets are mostly vegetarian. The objectives of the study were to investigate cobalamin and folate intake and status, and to explore associations with socio-demographics, anthropometrics, anemia, and dietary habits. Following a random selection of geographical clusters, we collected blood samples from 500 non-pregnant women and 24-h dietary recalls and food frequency questionnaires from a subsample of 379 women. Twenty percent of the women did not consume any food containing cobalamin during the days recalled, and in 72% nutritional cobalamin intake was <1 mu g/day. Eighty-four percent of the women had cobalamin intake lower than the estimated average requirement (EAR) (< 2 mu g/day). In contrast, only 12% of the women had a folate intake less than 100 mu g per day, whereas 62% had intake between 100 and 320 mu g. Low plasma cobalamin (< 150 pmol/L) was found in 42% of the women, most of whom (88%) also had elevated levels of methylmalonic acid. Our results indicated a high prevalence of nutritional cobalamin deficiency, while folate deficiency was uncommon.
21.	Chuang, Shu-Chun, et al. (författare) A U-shaped relationship between plasma folate and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition 2011 Ingår i: European Journal of Cancer. - Oxford : Pergamon. - 0959-8049 .- 1879-0852. ; 47:12, s. 1808-1816 Tidskriftsartikel (refereegranskat)abstract Folate intake has shown an inverse association with pancreatic cancer; nevertheless, results from plasma measurements were inconsistent. The aim of this study is to examine the association between plasma total homocysteine, methionine, folate, cobalamin, pyridoxal 5'-phosphate, riboflavin, flavin mononucleotide and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). We conducted a nested case-control study in the EPIC cohort, which has an average of 9.6 years of follow-up (1992-2006), using 463 incident pancreatic cancer cases. Controls were matched to each case by center, sex, age (+/- 1 year), date (+/- 1 year) and time (+/- 3 h) at blood collection and fasting status. Conditional logistic regression was used to calculate the odds ratios (OR) and 95% confidence intervals (CI), adjusting for education, smoking status, plasma cotinine concentration, alcohol drinking, body mass index and diabetes status. We observed a U-shaped association between plasma folate and pancreatic cancer risk. The ORs for plasma folate <= 5, 5-10, 10-15 (reference), 15-20, and > 20 nmol/L were 1.58 (95% CI = 0.72-3.46), 1.39 (0.93-2.08), 1.0 (reference), 0.79 (0.52-1.21), and 1.34 (0.89-2.02), respectively. Methionine was associated with an increased risk in men (per quintile increment: OR = 1.17, 95% CI = 1.00-1.38) but not in women (OR = 0.91, 95% CI = 0.78-1.07; p for heterogeneity < 0.01). Our results suggest a U-shaped association between plasma folate and pancreatic cancer risk in both men and women. The positive association that we observed between methionine and pancreatic cancer may be sex dependent and may differ by time of follow-up. However, the mechanisms behind the observed associations warrant further investigation.
22.	Chuang, Shu-Chun, et al. (författare) Circulating Biomarkers of Tryptophan and the Kynurenine Pathway and Lung Cancer Risk 2014 Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 23:3, s. 461-468 Tidskriftsartikel (refereegranskat)abstract Background: Imbalances in tryptophan metabolism have been linked to cancer-related immune escape and implicated in several cancers, including lung cancer. Methods: We conducted a nested case-control study within the European Prospective Investigation into Cancer andNutrition (EPIC) that included 893 incident lung cancer cases and 1,748matched controls. Circulating levels of tryptophan and six of its metabolites were measured and evaluated in relation to lung cancer risk. Results: Tryptophan (P-trend = 2 Chi 10(-5)) and the kynurenine/ tryptophan ratio (KTR; P-trend 4 Chi 10(-5)) were associated with lung cancer risk overall after adjusting for established risk factors. The ORs comparing the fifth and first quintiles (OR5th (vs. 1st)) were 0.52 [ 95% confidence interval (CI), 0.37-0.74] for tryptophan and 1.74 (95% CI, 1.24-2.45) for KTR. After adjusting for plasma methionine (available fromprevious work, which was strongly correlated with tryptophan), the associations of tryptophan (adjusted P-trend 0.13) and KTR (P-trend = 0.009) were substantially attenuated. KTR was positively associated with squamous cell carcinoma, the OR5th vs. 1st being 2.83 (95% CI, 1.62-4.94, P-trend -3 Chi 10(-5)) that was only marginally affected by adjusting for methionine. Conclusions: This study indicates that biomarkers of tryptophan metabolism are associated with subsequent lung cancer risk. Although this result would seem consistent with the immune system having a role in lung cancer development, the overall associations were dependent on methionine, and further studies are warranted to further elucidate the importance of these metabolites in lung cancer etiology. Impact: This is the first prospective study investigating the tryptophan pathway in relation to lung cancer risk.
23.	Eussen, Simone J, et al. (författare) Effect of oral vitamin B-12 with or without folic acid on cognitive function in older people with mild vitamin B-12 deficiency : a randomized, placebo-controlled trial. 2006 Ingår i: Am J Clin Nutr. - 0002-9165. ; 84:2, s. 361-70 Tidskriftsartikel (populärvet., debatt m.m.)
24.	Gylling, Björn, et al. (författare) Vitamin B-6 and colorectal cancer risk : a prospective population-based study using 3 distinct plasma markers of vitamin B-6 status 2017 Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 105:4, s. 897-904 Tidskriftsartikel (refereegranskat)abstract Background: Higher plasma concentrations of the vitamin B-6 marker pyridoxal 5#-phosphate (PLP) have been associated with reduced colorectal cancer (CRC) risk. Inflammatory processes, including vitamin B-6 catabolism, could explain such findings. Objective: We investigated 3 biomarkers of vitamin B-6 status in relation to CRC risk. Design: This was a prospective case-control study of 613 CRC cases and 1190 matched controls nested within the Northern Sweden Health and Disease Study (n = 114,679). Participants were followed from 1985 to 2009, and the median follow-up from baseline to CRC diagnosis was 8.2 y. PLP, pyridoxal, pyridoxic acid (PA), 3-hydroxykynurenine, and xanthurenic acids (XAs) were measured in plasma with the use of liquid chromatography-tandem mass spectrometry. We calculated relative and absolute risks of CRC for PLP and the ratios 3-hydroxykynurenine: XA (HK: XA), an inverse marker of functional vitamin B-6 status, and PA:(PLP + pyridoxal) (PAr), a marker of inflammation and oxidative stress and an inverse marker of vitamin B-6 status. Results: Plasma PLP concentrations were associated with a reduced CRC risk for the third compared with the first quartile and for PLP sufficiency compared with deficiency [OR: 0.60 (95% CI: 0.44, 0.81) and OR: 0.55 (95% CI: 0.37, 0.81), respectively]. HK: XA and PAr were both associated with increased CRC risk [OR: 1.48 (95% CI: 1.08, 2.02) and OR: 1.50 (95% CI: 1.10, 2.04), respectively] for the fourth compared with the first quartile. For HK: XA and PAr, the findings were mainly observed in study participants with,10.5 y of follow-up between sampling and diagnosis. Conclusions: Vitamin B-6 deficiency as measured by plasma PLP is associated with a clear increase in CRC risk. Furthermore, our analyses of novel markers of functional vitamin B-6 status and vitamin B-6-associated oxidative stress and inflammation suggest a role in tumor progression rather than initiation.
25.	Hin, Harold, et al. (författare) Clinical relevance of low serum vitamin B12 concentrations in older people : the Banbury B12 study 2006 Ingår i: Age and Ageing. - London : Oxford University Press. - 0002-0729 .- 1468-2834. ; 35:4, s. 416-422 Tidskriftsartikel (refereegranskat)abstract Background: low vitamin B12 concentrations are common in older people, but the clinical relevance of biochemical evidence of vitamin B12 deficiency in the absence of anaemia is uncertain. Objective: to examine associations of cognitive impairment, depression and neuropathy with blood measurements of vitamin B12 and folate status in older people. Design: cross-sectional study in general practice in Banbury, England. Participants: a total of 1,000 individuals aged 75 years or older living in the community. Results: low vitamin B12 concentrations were identified in 13% of older people and were associated with memory impairment and depression. After adjustment for age, sex and smoking, individuals with vitamin B12 or holotranscobalamin (holoTC) in the bottom compared with top quartiles had a 2-fold risk (OR = 2.17; 95% CI 1.11-4.27) and a 3-fold risk (OR = 3.02; 95% CI 1.31-6.98) of cognitive impairment, respectively. Low vitamin B12 status was also associated with missing ankle tendon jerks but not with depression. Treatment with vitamin B12 for 3 months corrected the biochemical abnormalities but had no effect on any of the clinical measurements. Conclusions: low vitamin B12 concentrations are associated with cognitive impairment and missing ankle tendon jerks in older people in the absence of anaemia. Large-scale trials of vitamin B12 supplementation are required to assess the clinical significance of these associations.
26.	Johansson, Mattias, et al. (författare) Circulating Biomarkers of One-Carbon Metabolism in Relation to Renal Cell Carcinoma Incidence and Survival 2014 Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 106:12 Tidskriftsartikel (refereegranskat)abstract Background: The etiology of renal cell carcinoma (RCC) is only partially understood, but a metabolic component appears likely. We investigated biomarkers of one-carbon metabolism and RCC onset and survival. Methods: The European Prospective Investigation into Cancer and Nutrition (EPIC) recruited 385 747 participants with blood samples between 1992 and 2000, and this analysis included 556 RCC case-control pairs. A subsequent replication study included 144 case-control pairs nested within the Melbourne Collaborative Cohort Study (MCCS). Plasma concentrations of vitamin B2, vitamin B6, folate, vitamin B12, methionine and homocysteine were measured in prediagnostic samples and evaluated with respect to RCC risk using conditional and unconditional logistic regression models, and to all-cause mortality in RCC cases using Cox regression models. All statistical tests were two-sided. Results: EPIC participants with higher plasma concentrations of vitamin B6 had lower risk of RCC, the odds ratio comparing the 4th and 1st quartiles (OR4vs1) being 0.40 95% confidence interval [CI] = 0.28 to 0.57, P-trend < .001. We found similar results after adjusting for potential confounders (adjusted P-trend < .001). In survival analysis, the hazard ratio for all-cause mortality in RCC cases when comparing the 4th and 1st quartiles (HR4vs1) of vitamin B6 was 0.57 (95% CI = 0.37 to 0.87, P-trend < .001). Subsequent replication of these associations within the MCCS yielded very similar results for both RCC risk (OR4vs1 = 0.47, 95% CI = 0.23 to 0.99, P-trend = .07) and all-cause mortality (HR4vs1 = 0.56, 95% CI = 0.27 to 1.17, P-trend = .02). No association was evident for the other measured biomarkers. Conclusion: Study participants with higher circulating concentrations of vitamin B6 had lower risk of RCC and improved survival following diagnosis in two independent cohorts.
27.	Johansson, Mattias, et al. (författare) Circulating concentrations of folate and vitamin B12 in relation to prostate cancer risk : results from the European prospective investigation into cancer and nutrition study 2008 Ingår i: Cancer Epidemiol Biomarkers Prev. - 1055-9965. ; 17:2, s. 279-285 Tidskriftsartikel (refereegranskat)abstract Background: Determinants of one-carbon metabolism, such as folate and vitamin B12, have been implicated in cancer development. Previous studies have not provided conclusive evidence for the importance of circulating concentrations of folate and vitamin B12 in prostate cancer etiology. The aim of the present study was to investigate the relationship between prostate cancer risk and circulating concentrations of folate and vitamin B12 in a large prospective cohort. Methods: We analyzed circulating concentrations of folate and vitamin B12 in 869 cases and 1,174 controls, individually matched on center, age, and date of recruitment, nested within the European Prospective Investigation into Cancer and Nutrition cohort. Relative risks (RR) for prostate cancer were estimated using conditional logistic regression models. Results: Overall, no significant associations were observed for circulating concentrations of folate (Ptrend = 0.62) or vitamin B12 (Ptrend = 0.21) with prostate cancer risk. RRs for a doubling in folate and vitamin B12 concentrations were 1.03 [95% confidence interval (95% CI), 0.92-1.16] and 1.12 (95% CI, 0.94-1.35), respectively. In the subgroup of cases diagnosed with advanced stage prostate cancer, elevated concentrations of vitamin B12 were associated with increased risk (RR for a doubling in concentration, 1.69; 95% CI, 1.05-2.72, Ptrend = 0.03). No other subgroup analyses resulted in a statistically significant association. Conclusion: This study does not provide strong support for an association between prostate cancer risk and circulating concentrations of folate or vitamin B12. Elevated concentrations of vitamin B12 may be associated with an increased risk for advanced stage prostate cancer, but this association requires examination in other large prospective studies. (Cancer Epidemiol Biomarkers Prev 2007;17(2):279–85)
28.	Johansson, Mattias, et al. (författare) One-carbon metabolism and prostate cancer risk : prospective investigation of seven circulating B vitamins and metabolites 2009 Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 18:5, s. 1538-1543 Tidskriftsartikel (refereegranskat)abstract PURPOSE: Components of one-carbon metabolism are believed to influence cancer development with suggested mechanisms, including DNA methylation and DNA repair mechanisms. However, few prospective studies have investigated one-carbon metabolism in relation to prostate cancer risk, and the results have been conflicting. The aim of this study was to do a comprehensive investigation of the components of one-carbon metabolism in relation to prostate cancer risk. A panel of seven circulating B vitamins and related metabolites was selected, most of which have not been studied before. MATERIALS AND METHODS: We analyzed plasma concentrations of betaine, choline, cysteine, methionine, methylmalonic acid (MMA), vitamin B2, and vitamin B6 in 561 cases and 1,034 controls matched for age and recruitment date, nested within the population-based Northern Sweden Health and Disease Cohort. Relative risks of prostate cancer were estimated by conditional logistic regression. RESULTS: Positive associations with prostate cancer risk were observed for choline and vitamin B2, and an inverse association was observed for MMA. The relative risks for a doubling in concentrations were 1.46 [95% confidence interval (95% CI), 1.04-2.05; P(trend) = 0.03] for choline, 1.11 (95% CI, 1.00-1.23; P(trend) = 0.04) for vitamin B2, and 0.78 (95% CI, 0.63-0.97; P(trend) = 0.03) for MMA. Concentrations of betaine, cysteine, methionine, and vitamin B6 were not associated with prostate cancer risk. CONCLUSION: The results of this large prospective study suggest that elevated plasma concentrations of choline and vitamin B2 may be associated with an increased risk of prostate cancer. These novel findings support a role of one-carbon metabolism in prostate cancer etiology and warrant further investigation. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1538-43).
29.	Johansson, Mattias, et al. (författare) Prospective investigation of one-carbon metabolism in relation to prostate cancer risk : results from the NSHDC study Annan publikation (övrigt vetenskapligt/konstnärligt)
30.	Larose, Tricia L., et al. (författare) Circulating cotinine concentrations and lung cancer risk in the Lung Cancer Cohort Consortium (LC3) 2018 Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 47:6, s. 1760-1771 Tidskriftsartikel (refereegranskat)abstract Background: Self-reported smoking is the principal measure used to assess lung cancer risk in epidemiological studies. We evaluated if circulating cotinine—a nicotine metabolite and biomarker of recent tobacco exposure—provides additional information on lung cancer risk.Methods: The study was conducted in the Lung Cancer Cohort Consortium (LC3) involving 20 prospective cohort studies. Pre-diagnostic serum cotinine concentrations were measured in one laboratory on 5364 lung cancer cases and 5364 individually matched controls. We used conditional logistic regression to evaluate the association between circulating cotinine and lung cancer, and assessed if cotinine provided additional risk-discriminative information compared with self-reported smoking (smoking status, smoking intensity, smoking duration), using receiver-operating characteristic (ROC) curve analysis.Results: We observed a strong positive association between cotinine and lung cancer risk for current smokers [odds ratio (OR ) per 500 nmol/L increase in cotinine (OR500): 1.39, 95% confidence interval (CI): 1.32–1.47]. Cotinine concentrations consistent with active smoking (≥115 nmol/L) were common in former smokers (cases: 14.6%; controls: 9.2%) and rare in never smokers (cases: 2.7%; controls: 0.8%). Former and never smokers with cotinine concentrations indicative of active smoking (≥115 nmol/L) also showed increased lung cancer risk. For current smokers, the risk-discriminative performance of cotinine combined with self-reported smoking (AUCintegrated: 0.69, 95% CI: 0.68–0.71) yielded a small improvement over self-reported smoking alone (AUCsmoke: 0.66, 95% CI: 0.64–0.68) (P = 1.5x10–9).Conclusions: Circulating cotinine concentrations are consistently associated with lung cancer risk for current smokers and provide additional risk-discriminative information compared with self-report smoking alone.
31.	Leenders, Max, et al. (författare) Plasma cotinine levels and pancreatic cancer in the EPIC cohort study 2012 Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 131:4, s. 997-1002 Tidskriftsartikel (refereegranskat)abstract Smoking is an established risk factor for pancreatic cancer, previously investigated by the means of questionnaires. Using cotinine as a biomarker for tobacco exposure allows more accurate quantitative analyses to be performed. This study on pancreatic cancer, nested within the European Prospective Investigation into Cancer and Nutrition (EPIC cohort), included 146 cases and 146 matched controls. Using liquid chromatography-mass spectrometry, plasma cotinine levels were analyzed on average 8.0 years before cancer onset (595% range: 2.812.0 years). The relation between plasma cotinine levels and pancreatic cancer was analyzed with conditional logistic regression for different levels of cotinine in a population of never and current smokers. This was also done for the self-reported number of smoked cigarettes per day at baseline. Every increase of 350 nmol/L of plasma cotinine was found to significantly elevate risk of pancreatic cancer [odds ratio (OR): 1.33, 95% confidence interval (CI): 1.111.60]. People with a cotinine level over 1187.8 nmol/L, a level comparable to smoking 17 cigarettes per day, have an elevated risk of pancreatic cancer, compared to people with cotinine levels below 55 nmol/L (OR: 3.66, 95% CI: 1.449.26). The results for self-reported smoking at baseline also show an increased risk of pancreatic cancer from cigarette smoking based on questionnaire information. People who smoke more than 30 cigarettes per day showed the highest risk compared to never smokers (OR: 4.15, 95% CI: 1.0216.42). This study is the first to show that plasma cotinine levels are strongly related to pancreatic cancer.
32.	Manger, Mari S., et al. (författare) Cobalamin Status Modifies the Effect of Zinc Supplementation on the Incidence of Prolonged Diarrhea in 6-to 30-Month-Old North Indian Children 2011 Ingår i: Journal of Nutrition. - : Elsevier BV. - 0022-3166 .- 1541-6100. ; 141:6, s. 1108-1113 Tidskriftsartikel (refereegranskat)abstract The observed effect of zinc supplementation on diarrheal morbidity varies between trials and there is a need to identify subgroups most likely to benefit from improved zinc nutriture. In a randomized, double-blind trial in 2296 children in New Delhi, India, we assessed whether baseline cobalamin or folate status modified the effect of zinc supplementation on the incidence of prolonged (>= 7 d duration) and acute diarrhea. Children aged 6-30 mo received zinc or placebo daily for 4 mo. We measured plasma concentrations of folate, cobalamin, total homocysteine (tHcy), and methylmalonic acid (MMA) at enrollment and assessed the efficacy of zinc supplementation in subgroups based on these variables. The efficacy of zinc on reducing the risk of prolonged diarrhea was higher in those with plasma cobalamin concentrations below the 25th percentile and in those with tHcy and MMA concentrations above the 75th percentile. The OR (95% Cl) for children below and above the 25th percentile for cobalamin were 0.53 (0.35-0.78) and 0.90 (0.73-1.11), respectively (P-interaction = 0.015). There were similar differences for the OR when comparing efficacy in those above and below the 75th percentile for tHcy and MMA (P-interaction = 0.045 and 0.188, respectively). Baseline folate status did not modify the effect of zinc on prolonged diarrhea. Neither cobalamin nor folate status influenced the effect of zinc on acute diarrhea. Children with poor cobalamin status benefited more from zinc supplementation for the prevention of prolonged diarrhea J. Nutr. 141: 1108-1113, 2011.
33.	Manger, Mari S., et al. (författare) Poor Folate Status Predicts Persistent Diarrhea in 6-to 30-Month-Old North Indian Children 2011 Ingår i: Journal of Nutrition. - Bethesda : American Society for Nutrition. - 0022-3166 .- 1541-6100. ; 141:12, s. 2226-2232 Tidskriftsartikel (refereegranskat)abstract Poor micronutrient status is associated with diarrheal illness, but it is not known whether low folate and/or cobalamin status are independent risk factors for diarrhea. We measured the association between plasma folate and cobalamin and subsequent diarrheal morbidity in a prospective cohort study of 2296 children aged 6-30 mo in New Delhi, India. Plasma concentrations of folate, cobalamin, total homocysteine (tHcy), and methylmalonic acid were determined at baseline. Whether a child had diarrhea was recorded during weekly visits in a 4-mo zinc supplementation trial. Diarrhea episodes lasting <7, >= 7, and >= 14 d were classified as acute, prolonged, and persistent, respectively. There was a total of 4596 child periods with acute, 633 with prolonged, and 117 with persistent diarrhea during follow-up. Children with plasma folate concentrations in the lowest quartile had higher odds of persistent diarrhea than children in the other quartiles [adjusted OR = 1.77(95% CI = 1.14, 2.75); P = 0.01]. This effect differed between boys [adjusted OR = 2.51 (95% CI = 1.47, 4.28)] and girls [adjusted OR = 1.03 (95% CI = 0.53, 2.01); P-interaction = 0.030]. We found a small but significant association between high plasma tHcy concentration and acute diarrhea [adjusted OR = 1.14 (95% CI = 1.04, 1.24); P = 0.006]. Plasma cobalamin concentration was not a predictor of diarrheal morbidity. In conclusion, poor folate status was an independent predictor of persistent diarrhea in this population. J. Nutr. 141: 2226-2232, 2011.
34.	Manjer, Jonas, et al. (författare) Vitamins B2 and B6 and genetic polymorphisms related to one-carbon metabolism as risk factors for gastric adenocarcinoma in the European prospective investigation into cancer and nutrition. 2010 Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 19:1, s. 28-38 Tidskriftsartikel (refereegranskat)abstract B vitamins and polymorphisms in genes coding for enzymes involved in one-carbon metabolism may affect DNA synthesis and methylation and thereby be implicated in carcinogenesis. Previous data on vitamins B2 and B6 and genetic polymorphisms other than those involving MTHFR as risk factors for gastric cancer (GC) are sparse and inconsistent. In this case-control study nested within the European Prospective Investigation into Cancer and Nutrition cohort, cases (n = 235) and controls (n = 601) were matched for study center, age, sex, and time of blood sampling. B2 and B6 species were measured in plasma, and the sum of riboflavin and flavin mononucleotide was used as the main exposure variable for vitamin B2 status, whereas the sum of pyridoxal 5'-phosphate, pyridoxal, and 4-pyridoxic acid was used to define vitamin B6 status. In addition, we determined eight polymorphisms related to one-carbon metabolism. Relative risks for GC risk were calculated with conditional logistic regression, adjusted for Helicobacter pylori infection status and smoking status. Adjusted relative risks per quartile (95% confidence interval, P(trend)) were 0.85 (0.72-1.01, 0.06) for vitamin B2 and 0.78 (0.65-0.93, <0.01) for vitamin B6. Both relations were stronger in individuals with severe chronic atrophic gastritis. The polymorphisms were not associated with GC risk and did not modify the observed vitamin-cancer associations. In summary, results from this large European cohort study showed an inverse association between vitamin B2 and GC risk, which is borderline significant, and a significant inverse association between vitamin B6 and GC risk.
35.	Midttun, Oivind, et al. (författare) Multianalyte quantification of vitamin B6 and B2 species in the nanomolar range in human plasma by liquid chromatography-tandem mass spectrometry. 2005 Ingår i: Clin Chem. - 0009-9147. ; 51:7, s. 1206-16 Tidskriftsartikel (refereegranskat)
36.	Midttun, Øivind, et al. (författare) A cross-sectional study of inflammatory markers as determinants of circulating kynurenines in the Lung Cancer Cohort Consortium 2023 Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13:1 Tidskriftsartikel (refereegranskat)abstract Circulating concentrations of metabolites (collectively called kynurenines) in the kynurenine pathway of tryptophan metabolism increase during inflammation, particularly in response to interferon-gamma (IFN-γ). Neopterin and the kynurenine/tryptophan ratio (KTR) are IFN-γ induced inflammatory markers, and together with C-reactive protein (CRP) and kynurenines they are associated with various diseases, but comprehensive data on the strength of associations of inflammatory markers with circulating concentrations of kynurenines are lacking. We measured circulating concentrations of neopterin, CRP, tryptophan and seven kynurenines in 5314 controls from 20 cohorts in the Lung Cancer Cohort Consortium (LC3). The associations of neopterin, KTR and CRP with kynurenines were investigated using regression models. In mixed models, one standard deviation (SD) higher KTR was associated with a 0.46 SD higher quinolinic acid (QA), and 0.31 SD higher 3-hydroxykynurenine (HK). One SD higher neopterin was associated with 0.48, 0.44, 0.36 and 0.28 SD higher KTR, QA, kynurenine and HK, respectively. KTR and neopterin respectively explained 24.1% and 16.7% of the variation in QA, and 11.4% and 7.5% of HK. CRP was only weakly associated with kynurenines in regression models. In summary, QA was the metabolite that was most strongly associated with the inflammatory markers. In general, the inflammatory markers were most strongly related to metabolites located along the tryptophan-NAD axis, which may support suggestions of increased production of NAD from tryptophan during inflammation.
37.	Midttun, Öivind, et al. (författare) Plasma vitamin B-6 forms and their relation to transsulfuration metabolites in a large, population-based study 2007 Ingår i: American Journal of Clinical Nutrition. - Bethesda : American society for nutrition. - 0002-9165 .- 1938-3207. ; 86:1, s. 131-138 Tidskriftsartikel (refereegranskat)abstract Background: Vitamin B-6 exists in different forms; one of those forms, pyridoxal 5'-phosphate (PLP), serves a cofactor in many enzyme reactions, including the transsulfuration pathway, in which homocysteine is converted to cystathionine and then to cysteine. Data on the relations between indexes of vitamin B-6 status and transsulfuration metabolites in plasma are sparse and conflicting.Objective: We investigated the distribution and associations of various vitamin B-6 species in plasma and their relation to plasma concentrations of transsulfuration metabolites.Design: Nonfasting blood samples from 10 601 healthy subjects with a mean age of 56.4 y were analyzed for all known vitamin B-6 vitamers, folate, cobalamin, riboflavin, total homocysteine, cystathionine, total cysteine, methionine, and creatinine. All subjects were genotyped for the methylenetetrahydrofolate reductase (MTHFR) 677C -> T polymorphism.Results: Plasma concentrations of the main vitamin B-6 vitamers-PLP, pyridoxal, and 4-pyridoxic acid-were strongly correlated. Among the vitamin B-6 vitamers, PLP showed the strongest and most consistent inverse relation to total homocysteine and cystathionine, but the dose response was different for the 2 metabolites. The PLP-total homocysteine relation was significant only in the lowest quartile of the vitamin B-6 distribution and was strongest in subjects with the MTHFR 677TT genotype, whereas cystathionine showed a graded response throughout the range of vitamin B-6 vitamer concentrations, and the effect was not modified by the MTHFR 677C -> T genotype.Conclusion: This large population-based study provided precise estimates of the relation between plasma concentrations of vitamin B-6 forms and transsulfuration metabolites as modified by the MTHFR 677C -> T genotype.
38.	Muller, David C., et al. (författare) Circulating high sensitivity C reactive protein concentrations and risk of lung cancer : nested case-control study within Lung Cancer Cohort Consortium 2019 Ingår i: The BMJ. - : BMJ Publishing Group Ltd. - 1756-1833 .- 0959-8138. ; 364 Tidskriftsartikel (refereegranskat)abstract Objectives To conduct a comprehensive analysis of prospectively measured circulating high sensitivity C reactive protein (hsCRP) concentration and risk of lung cancer overall, by smoking status (never, former, and current smokers), and histological sub-type.Design Nested case-control study.Setting 20 population based cohort studies in Asia, Europe, Australia, and the United States.Participants 5299 patients with incident lung cancer, with individually incidence density matched controls.Exposure Circulating hsCRP concentrations in prediagnostic serum or plasma samples.Main outcome measure Incident lung cancer diagnosis.Results A positive association between circulating hsCRP concentration and the risk of lung cancer for current (odds ratio associated with a doubling in hsCRP concentration 1.09, 95% confidence interval 1.05 to 1.13) and former smokers (1.09, 1.04 to 1.14) was observed, but not for never smokers (P<0.01 for interaction). This association was strong and consistent across all histological subtypes, except for adenocarcinoma, which was not strongly associated with hsCRP concentration regardless of smoking status (odds ratio for adenocarcinoma overall 0.97, 95% confidence interval 0.94 to 1.01). The association between circulating hsCRP concentration and the risk of lung cancer was strongest in the first two years of follow-up for former and current smokers. Including hsCRP concentration in a risk model, in addition to smoking based variables, did not improve risk discrimination overall, but slightly improved discrimination for cancers diagnosed in the first two years of follow-up.Conclusions Former and current smokers with higher circulating hsCRP concentrations had a higher risk of lung cancer overall. Circulating hsCRP concentration was not associated with the risk of lung adenocarcinoma. Circulating hsCRP concentration could be a prediagnostic marker of lung cancer rather than a causal risk factor.
39.	Price, Alison J, et al. (författare) Circulating Folate and Vitamin B12 and Risk of Prostate Cancer : A Collaborative Analysis of Individual Participant Data from Six Cohorts Including 6875 Cases and 8104 Controls. 2016 Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 70:6, s. 941-951 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Folate and vitamin B12 are essential for maintaining DNA integrity and may influence prostate cancer (PCa) risk, but the association with clinically relevant, advanced stage, and high-grade disease is unclear.OBJECTIVE: To investigate the associations between circulating folate and vitamin B12 concentrations and risk of PCa overall and by disease stage and grade.DESIGN, SETTING, AND PARTICIPANTS: A study was performed with a nested case-control design based on individual participant data from six cohort studies including 6875 cases and 8104 controls; blood collection from 1981 to 2008, and an average follow-up of 8.9 yr (standard deviation 7.3). Odds ratios (ORs) of incident PCa by study-specific fifths of circulating folate and vitamin B12 were calculated using multivariable adjusted conditional logistic regression.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Incident PCa and subtype by stage and grade.RESULTS AND LIMITATIONS: Higher folate and vitamin B12 concentrations were associated with a small increase in risk of PCa (ORs for the top vs bottom fifths were 1.13 [95% confidence interval (CI), 1.02-1.26], ptrend=0.018, for folate and 1.12 [95% CI, 1.01-1.25], ptrend=0.017, for vitamin B12), with no evidence of heterogeneity between studies. The association with folate varied by tumour grade (pheterogeneity<0.001); higher folate concentration was associated with an elevated risk of high-grade disease (OR for the top vs bottom fifth: 2.30 [95% CI, 1.28-4.12]; ptrend=0.001), with no association for low-grade disease. There was no evidence of heterogeneity in the association of folate with risk by stage or of vitamin B12 with risk by stage or grade of disease (pheterogeneity>0.05). Use of single blood-sample measurements of folate and B12 concentrations is a limitation.CONCLUSIONS: The association between higher folate concentration and risk of high-grade disease, not evident for low-grade disease, suggests a possible role for folate in the progression of clinically relevant PCa and warrants further investigation.PATIENT SUMMARY: Folate, a vitamin obtained from foods and supplements, is important for maintaining cell health. In this study, however, men with higher blood folate levels were at greater risk of high-grade (more aggressive) prostate cancer compared with men with lower folate levels. Further research is needed to investigate the possible role of folate in the progression of this disease.
40.	Refsum, Helga, et al. (författare) Screening for serum total homocysteine in newborn children. 2004 Ingår i: Clin Chem. - 0009-9147. ; 50:10, s. 1769-84 Tidskriftsartikel (refereegranskat)
41.	Strand, Tor A., et al. (författare) Cobalamin and folate status predicts mental development scores in North Indian children 12-18 mo of age 2013 Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 97:2, s. 310-317 Tidskriftsartikel (refereegranskat)abstract Background: Micronutrient deficiencies can affect cognitive function. Many young children in low-and middle-income countries have inadequate cobalamin (vitamin B-12) status. Objective: The objective was to measure the association of plasma concentrations of folate, cobalamin, total homocysteine, and methylmalonic acid with cognitive performance at 2 occasions, 4 mo apart, in North Indian children aged 12-18 mo. Design: Bayley Scales of Infant Development II were used to assess cognition. In multiple regression models adjusted for several potential confounders, we measured the association between biomarkers for folate and cobalamin status and psychomotor or mental development scores on the day of blood sampling and 4 mo thereafter. Results: Each 2-fold increment in plasma cobalamin concentration was associated with a significant increment in the mental development index score of 1.3 (95% CI: 0.2, 2.4; P = 0.021). Furthermore, each 2-fold increment in homocysteine or methylmalonic acid concentration was associated with a decrement in mental development index score of 2.0 (95% CI: 0.5, 3.4; P = 0.007) or 1.1 (95% CI: 0.3, 1.8; P = 0.004) points, respectively. Plasma folate concentration was significantly and independently associated with mental development index scores only when children with poor cobalamin status were excluded, ie, in those who had cobalamin concentrations below the 25th percentile. None of these markers was associated with psychomotor scores in the multiple regression models. Conclusions: Cobalamin and folate status showed a statistically significant association with cognitive performance. Given the high prevalence of deficiencies in these nutrients, folate and cobalamin supplementation trials are required to measure any beneficial effect on cognition. The study was registered at www.clinicaltrials.gov under the identifier number NCT00272116. Am J Clin Nutr 2013;97:310-7.
42.	Strand, Tor A, et al. (författare) Folate, but not vitamin B-12 status, predicts respiratory morbidity in north Indian children. 2007 Ingår i: American Journal of Clinical Nutrition. - 0002-9165 .- 1938-3207. ; 86:1, s. 139-144 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Vitamin deficiencies are often part of malnutrition, which predisposes to acute lower respiratory tract infections. OBJECTIVE: The objective was to measure the association between cobalamin and folate status and subsequent respiratory morbidity. DESIGN: A prospective cohort study was conducted in 2482 children aged 6-30 mo nested in a zinc supplementation trial. We measured plasma concentrations of folate, cobalamin, methylmalonic acid, and total homocysteine (tHcy) and followed the children for 4 mo. RESULTS: We observed 1176 episodes of acute lower respiratory tract infections. Children with folate concentrations in the lowest quartile (interquartile range: 6.4-20.0 nmol/L) had a 44% higher incidence [adjusted incidence rate ratio (IRR): 1.44; 95% CI: 1.23, 1.70] of acute lower respiratory tract infections than did children in the other 3 quartiles. For tHcy, the IRR was 1.24 (1.07, 1.40) in a comparison of those in the highest quartile with those in the other quartiles. Breastfeeding was associated with high folate concentrations and protection against subsequent respiratory tract infections. This protection was significantly and substantially reduced after adjustment for plasma folate concentrations at baseline. Compared with the children in the other 3 quartiles, the IRR for being in the lowest quartile of cobalamin was 1.13 (0.76, 1.03) and for being in the highest quartile of methylmalonic acid was 1.12 (0.96, 1.31). CONCLUSIONS: Poor folate status appears to be an independent risk factor for lower respiratory tract infections in young children. This study also suggests that the protective effect of breastfeeding is partly mediated by folate provided through breast milk.
43.	Taneja, Sunita, et al. (författare) Cobalamin and folate status in infants and young children in a low-to-middle income community in India. 2007 Ingår i: American Journal of Clinical Nutrition. - 0002-9165 .- 1938-3207. ; 86:5, s. 1302-1309 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Population-based data on the prevalence of cobalamin and folate deficiency in India are lacking. OBJECTIVE: The objective was to measure the prevalence of cobalamin and folate deficiency among children aged 6-30 mo residing in a low-to-middle income community in North India. DESIGN: Children aged 6-30 mo (n = 2482) were identified through a community survey in a low-to-middle socioeconomic area in New Delhi, India. Non-fasting venous blood samples were collected before enrollment in another trial. RESULTS: The median (interquartile range; IQR) cobalamin concentration in 6-11-mo-old children was substantially lower in breastfed (183; 120-263 pmol/L) than in nonbreastfed (334; 235-463 pmol/L) children. Cobalamin concentrations decreased progressively with increasing age in the nonbreastfed children. Median (IQR) plasma folate concentrations in the 6-11-mo-old group were higher in breastfed (20.3; 11.7-34.4 nmol/L) than in nonbreastfed (5.3; 3.4-7.7 nmol/L) children (P < 0.001). Folate concentrations decreased with increasing age in the breastfed children. In the nonbreastfed children, folate concentrations increased with increasing age. Low concentrations of plasma cobalamin (<150 pmol/L) were detected in 36% of breastfed and 9% of nonbreastfed children (P < 0.001). The proportions of children with plasma folate concentrations <5 nmol/L in these 2 subgroups were 6% and 33%, respectively (P < 0.001). CONCLUSIONS: In north Indian preschool children, cobalamin and folate concentrations were commonly low and were associated with elevated total homocysteine and methylmalonic acid concentrations. Because low cobalamin and folate concentrations have functional consequences, population-based measures for improving cobalamin and folate concentrations need to be seriously considered.
44.	Timofeeva, Maria N, et al. (författare) Genetic polymorphisms in 15q25 and 19q13 loci, cotinine levels, and risk of lung cancer in EPIC 2011 Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 20:10, s. 2250-2261 Tidskriftsartikel (refereegranskat)abstract Backgrounds: Multiple polymorphisms affecting smoking behavior have been identified through genome-wide association studies. Circulating levels of the nicotine metabolite cotinine is a marker of recent smoking exposure. Hence, genetic variants influencing smoking behavior are expected to be associated with cotinine levels.METHODS: We conducted an analysis in a lung cancer case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. We investigated the effects of single-nucleotide polymorphisms (SNP) previously associated with smoking behavior on (i) circulating cotinine and (ii) lung cancer risk. A total of 894 cases and 1,805 controls were analyzed for cotinine and genotyped for 10 polymorphisms on 7p14, 8p11, 10q23, 15q25, and 19q13.RESULTS: Two variants in the nicotinic acetylcholine receptor subunit genes CHRNA5 and CHRNA3 on 15q25, rs16969968 and rs578776, were associated with cotinine (P = 0.001 and 0.03, respectively) in current smokers and with lung cancer risk (P < 0.001 and P = 0.001, respectively). Two 19q13 variants, rs7937 and rs4105144, were associated with increased cotinine (P = 0.003 and P < 0.001, respectively) but decreased lung cancer risk (P = 0.01 for both, after adjusting for cotinine). Variants in 7p14, 8p11, and 10q23 were not associated with cotinine or lung cancer risk.CONCLUSIONS: 15q25 and 19q13 SNPs were associated with circulating cotinine. The directions of association for 15q25 variants with cotinine were in accordance with that expected of lung cancer risk, whereas SNPs on 19q13 displayed contrasting associations of cotinine and lung cancer that require further investigation.Impact: This study is the largest to date investigating the effects of polymorphisms affecting smoking behavior on lung cancer risk using circulating cotinine measures as proxies for recent smoking behavior. Cancer Epidemiol Biomarkers Prev; ©2011 AACR.
45.	Ulvik, Arve, et al. (författare) Functional inference of the methylenetetrahydrofolate reductase 677 C > T and 1298A > C polymorphisms from a large-scale epidemiological study. 2007 Ingår i: Hum Genet. - 0340-6717. ; 121:1, s. 57-64 Tidskriftsartikel (refereegranskat)
46.	Vollset, Stein Emil, et al. (författare) The association of gastric cancer risk with plasma folate, cobalamin, and Methylenetetrahydrofolate reductase polymorphisms in the European prospective investigation into cancer and nutrition 2007 Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755. ; 16:11, s. 2416-2424 Tidskriftsartikel (refereegranskat)abstract Previous studies have shown inconsistent associations of folate intake and polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene with gastric cancer risk. Our nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort is the first prospective study of blood folate levels and gastric cancer. Gastric cancer cases (n = 247) and controls (n = 631) were matched for study center, age, sex, and time of blood donation. Two common single nucleotide polymorphisms of the MTHFR gene were determined, as were plasma concentrations of folate, cobalamin (vitamin B12), total homocysteine, and methylmalonic acid (cobalamin deficiency marker) in prediagnostic plasma. Risk measures were calculated with conditional logistic regression. Although no relations were observed between plasma folate or total homocysteine concentrations and gastric cancer, we observed a trend toward lower risk of gastric cancer with increasing cobalamin concentrations (odds ratio, 0.79 per SD increase in cobalamin; P = 0.01). Further analyses showed that the inverse association between cobalamin and gastric cancer was confined to cancer cases with low pepsinogen A levels (marker of severe chronic atrophic gastritis) at the time of blood sampling. The 677 C -> T MTHFR polymorphism was not associated with gastric cancer, but we observed an increased risk with the variant genotype of the 1298 A -> C polymorphism (odds ratio, 1.47 for CC versus AA; P = 0.04). In conclusion, we found no evidence of a role of folate in gastric cancer etiology. However, we observed increased gastric cancer risk at low cobalamin levels that was most likely due to compromised cobalamin status in atrophic gastritis preceding gastric cancer.
47.	Vollset, Stein Emil, et al. (författare) The association of gastric cancer risk with plasma folate, cobalamin, and methylenetetrahydrofolate reductase polymorphisms in the European prospective investigation into cancer and nutrition. 2007 Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1055-9965. ; 16:11, s. 2416-24 Tidskriftsartikel (refereegranskat)
48.	Watne, Leiv Otto, et al. (författare) Cerebrospinal fluid quinolinic acid is strongly associated with delirium and mortality in hip fracture patients. 2023 Ingår i: The Journal of clinical investigation. - 1558-8238. ; 133:2 Tidskriftsartikel (refereegranskat)abstract The kynurenine pathway (KP) has been identified as a potential mediator linking acute illness to cognitive dysfunction by generating neuroactive metabolites in response to inflammation. Delirium (acute confusion) is a common complication of acute illness and is associated with increased risk of dementia and mortality. However, the molecular mechanism underlying delirium, particularly in relation to the KP, remain elusive.We undertook a multi-center observational study with 586 hospitalized patients (248 with delirium) and investigated associations between delirium and KP metabolites measured in cerebrospinal fluid (CSF) and serum by targeted metabolomics. We also explored associations between KP metabolites and markers of neuronal damage and one-year mortality.In delirium, we found concentrations of the neurotoxic metabolite quinolinic acid in CSF (CSF-QA, OR 2.26 [1.78, 2.87], p<0.001) to be increased, as well as increases in several other KP metabolites in serum and CSF. In addition, CSF-QA was associated with the neuronal damage marker neurofilament light chain (NfL, β 0.43, p<0.001) and was a strong predictor of one-year mortality (HR 4.35 [2.93, 6.45] for CSF-QA ≥ 100 nmol/L, p<0.001). The associations between CSF-QA and delirium, neuronal damage, and mortality remained highly significant following adjustment for confounders and multiple comparisons.Our data identified how systemic inflammation, neurotoxicity, and delirium are strongly linked via the KP, and should inform future delirium prevention and treatment clinical trials that target enzymes of the KP.Norwegian Health Association and the South-Eastern Norway Regional Health Authorities.
49.	Zahed, Hana, et al. (författare) Epidemiology of 40 blood biomarkers of one-carbon metabolism, vitamin status, inflammation, and renal and endothelial function among cancer-free older adults 2021 Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 11:1 Tidskriftsartikel (refereegranskat)abstract Imbalances of blood biomarkers are associated with disease, and biomarkers may also vary non-pathologically across population groups. We described variation in concentrations of biomarkers of one-carbon metabolism, vitamin status, inflammation including tryptophan metabolism, and endothelial and renal function among cancer-free older adults. We analyzed 5167 cancer-free controls aged 40–80 years from 20 cohorts in the Lung Cancer Cohort Consortium (LC3). Centralized biochemical analyses of 40 biomarkers in plasma or serum were performed. We fit multivariable linear mixed effects models to quantify variation in standardized biomarker log-concentrations across four factors: age, sex, smoking status, and body mass index (BMI). Differences in most biomarkers across most factors were small, with 93% (186/200) of analyses showing an estimated difference lower than 0.25 standard-deviations, although most were statistically significant due to large sample size. The largest difference was for creatinine by sex, which was − 0.91 standard-deviations lower in women than men (95%CI − 0.98; − 0.84). The largest difference by age was for total cysteine (0.40 standard-deviation increase per 10-year increase, 95%CI 0.36; 0.43), and by BMI was for C-reactive protein (0.38 standard-deviation increase per 5-kg/m2 increase, 95%CI 0.34; 0.41). For 31 of 40 markers, the mean difference between current and never smokers was larger than between former and never smokers. A statistically significant (p < 0.05) association with time since smoking cessation was observed for 8 markers, including C-reactive protein, kynurenine, choline, and total homocysteine. We conclude that most blood biomarkers show small variations across demographic characteristics. Patterns by smoking status point to normalization of multiple physiological processes after smoking cessation.

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