| 51. |
- Dahlin, Anna M, 1979-, et al.
(författare)
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Plasma vitamin B12 concentrations and the risk of colorectal cancer : a nested case-referent study
- 2008
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 32:2, s. 304-314
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Tidskriftsartikel (refereegranskat)abstract
- In this nested case-referent study, we related plasma concentrations of vitamin B12 to the risk of colorectal cancer, taking into consideration prediagnostic plasma folate and total homocysteine concentrations. Subjects were 226 cases and double matched referents from the population-based Northern Sweden Health and Disease Study. Follow-up times from recruitment to diagnosis ranged from 0.1 to 12.7 years, with a median of 4.2 years. Plasma vitamin B12 concentrations were inversely associated with the risk of rectal cancer: univariate odds ratio for the highest versus lowest quintile 0.34 (95% confidence interval (95% CI) 0.13-0.83), p(trend) = 0.004. Risk estimates were attenuated slightly but remained statistically significant after adjustment for body mass index, current smoking, recreational and occupational physical activity, alcohol intake and prediagnostic plasma folate and total homocysteine concentrations: OR 0.30 (95% CI 0.08-0.99), p(trend) = 0.025. The corresponding univariate and fully adjusted odds ratios for colon cancer were 1.25 (CI 0.66-2.36), p(trend) = 0.185 and 1.42 (CI 0.67-3.05), p(trend) = 0.113, respectively. The observed over-risk was attributable to left-sided colon cancer. Interaction analyses including vitamin B12, folate and homocysteine were in line with the results for vitamin B12 alone. In conclusion, these results suggest that increasing levels of plasma vitamin B12, alone or together with other factors involved in one-carbon metabolism, may reduce the risk of rectal cancer, whereas for colon cancer, the association appears to be less clear.
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| 52. |
- Danielsson Niemi, Liza, 1976-
(författare)
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Host ligands and oral bacterial adhesion : studies on phosphorylated polypeptides and gp-340 in saliva and milk
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Infectious diseases e.g. gastric ulcer, caries and perodontitis, are caused by bacteria in a biofilm. Adhesion of bacteria to host ligands e.g. proteins, polypeptides and glycoproteins, is a key event in biofilm formation and colonization of surfaces such as mucosa and tooth tissues. Thus, host ligands could contribute to the susceptibility to infectious diseases. The general aim of this doctoral thesis was to study the effect of phosphorylated polypeptides and gp-340 in saliva and milk on oral bacterial adhesion and aggregation. Statherin is a non-glycosylated, phosphorylated polypeptide in saliva. The polypeptide inhibits precipitation and crystal growth of calcium phosphate and mediates adhesion of microorganisms. By using a hybrid peptide construct, the domain for adhesion of Actinomyces isolated from human infections and from rodents was found to reside in the C-terminal end, and the adhesion was inhibitable. With alanine substitution the peptide recognition epitope in the C-terminal end was delineated to Q and TF, where QAATF was an optimal inhibitory peptide. In contrast, human commensal Actinomyces bound to the middle region in a non-inhibitable fashion. Gp-340 is another protein in saliva, and it is a large, multifunctional glycoprotein. Four novel size variants (I-IV) of salivary gp-340 were distinguished within individuals, and their glycoforms were characterized. All four size variants were identical in the N-terminal amino acid sequence and shared core carbohydrates. Low-glyco lung gp-340, high-glyco saliva gp-340, and size variants I-III aggregated bacteria differently. Human milk, which shares many traits with saliva, could inhibit adhesion of Streptococcus mutans to saliva-coated hydroxyapatite (s-HA), a model for teeth, in an individually varying fashion. Human milk caseins, lactoferrin, secretory IgA, and IgG inhibited the binding avidly. By using synthetic peptides the inhibitory epitope in b-casein was mapped to a C-terminal stretch of 30 amino acids. Inhibition by human milk, secretory IgA and the b-casein-derived inhibitory peptide was universal among a panel of mutans streptococci. The main conclusions are: (i) statherin mediates differential binding of commensal versus infectious Actinomyces strains with small conformation-dependent binding epitopes, (ii) salivary gp-340 has individual polymorphisms that at least affect binding of bacteria, (iii) human milk inhibits S. mutans adhesion to s-HA in an individually varying fashion, and the C-terminal end of human milk β-casein is one inhibitory component. Together these results suggest that the studied host ligands can influence the composition of the oral biofilm. Statherin may protect the host from colonization of bacteria associated with infections. Gp-340 size variants may affect functions related to host innate immune defences such as interactions with a wide array of bacteria, and human milk may have a protective effect in infants from colonization of mutans streptococci.
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| 53. |
- Danielsson Niemi, Liza, 1976-, et al.
(författare)
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Human milk compounds inhibiting adhesion of mutans streptococci to host ligand-coated hydroxyapatite in vitro
- 2009
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Ingår i: Caries Research. - : S. Karger AG. - 0008-6568 .- 1421-976X. ; 43:3, s. 171-178
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Tidskriftsartikel (refereegranskat)abstract
- Acquisition of mutans streptococci at an early age is a risk factor for later caries development. Following our recent finding that human milk may inhibit adhesion of Streptococcus mutans the aim of the present study was to identify compounds in human milk preventing adhesion of mutans streptococci to saliva- or gp340-coated hydroxyapatite (s-HA and gp340-HA) using an in vitro model system. Superdex 200 fractions of human milk and purified proteins were screened for binding inhibition of the S. mutans strain Ingbritt. Avid inhibition was seen to both s-HA and gp340-HA for caseins, lactoferrin, IgA and IgG, and moderate inhibition for alpha-lactalbumin and bile salt-stimulated lipase, whereas albumin and lysozyme had no effect. The inhibitory epitope in beta-casein was delineated to its C-terminal LLNQELLNPTHQIYPVTQPLAPVHNPISV stretch by use of synthetic peptides. Similarly, a peptide (SCKFDEYFSQSCA) corresponding to the human lactoferrin stretch that is highly homologous to the previously shown inhibitory stretch of bovine lactoferrin was found to inhibit S. mutans Ingbritt binding. Inhibition by human milk, IgA, and the inhibitory beta-casein peptide was universal among 4 strains of S. mutans (Ingbritt, NG8, LT11, JBP) and 2 strains of S. sobrinus (6715 and OMZ176). IgG inhibited 4, alpha-lactalbumin 3 and lactoferrin 2 of these 6 strains. It was also confirmed that none of the milk components coated on HA mediated S. mutans Ingbritt adhesion, which was consistent with the finding that no milk protein was recognized on Western blots by gp340/DMBT1 monoclonal antibodies.
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| 54. |
- Danielsson Niemi, Liza, 1976-, et al.
(författare)
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Salivary statherin peptide-binding epitopes of commensal and potentially infectious Actinomyces spp. delineated by a hybrid peptide construct
- 2004
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Ingår i: Infection and Immunity. - 0019-9567 .- 1098-5522. ; 72:2, s. 782-787
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Forskningsöversikt (refereegranskat)abstract
- Adhesion of microorganisms to host receptor molecules such as salivary statherin molecules is a common event in oral microbial colonization. Here we used a hybrid peptide construct (with both a hydroxyapatite-binding portion and a test peptide portion) to map the interaction of Actinomyces species (and Candida albicans) with statherin. Adhesion to hybrid peptides and truncated statherin variants revealed three binding types, types I to III. (i) Type I strains of rat, hamster, and human infection origins bound C-terminal-derived QQYTF and PYQPQY peptides. The QQYTF peptide inhibited statherin binding for some strains but not for others. (ii) Type II strains of human and monkey tooth origins bound middle-region-derived YQPVPE and QPLYPQ peptides. Neither strain was inhibited by soluble peptides. (iii) Type III strains of human infection origins (and C. albicans) did not bind to either statherin-derived peptides or truncated statherin. Moreover, the type I strains inhibited by QQYTF were also inhibited by TF and QAATF peptides and were detached from statherin by the same peptides. In conclusion, it is suggested that commensal and potentially infectious microorganisms bind middle or C-terminal statherin differently and that other microbes might require discontinuous epitopes.
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| 55. |
- Debras, Charlotte, et al.
(författare)
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Dietary intake of dicarbonyl compounds and changes in body weight over time in a large cohort of European adults
- 2024
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Ingår i: British Journal of Nutrition. - : Cambridge University Press. - 0007-1145 .- 1475-2662.
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Tidskriftsartikel (refereegranskat)abstract
- Dicarbonyl compounds are highly reactive precursors of Advanced Glycation End-products (AGEs), produced endogenously, present in certain foods, and formed during food processing. AGEs contribute to development of adverse metabolic outcomes but health effects of dietary dicarbonyls are largely unexplored. We investigated associations between three dietary dicarbonyl compounds, methylglyoxal (MGO), glyoxal (GO), and 3-deoxyglucosone (3-DG), and body-weight changes in European adults. Dicarbonyl intakes were estimated using food composition database from 263,095 EPIC-PANACEA participants with two body-weight assessments (median follow-up time=5.4y). Associations between dicarbonyls and 5-year body-weight changes were estimated using mixed linear regression models. Stratified analyses by sex, age, and baseline BMI were performed. Risk of becoming overweight/obese was assessed using multivariable-adjusted logistic regression. MGO intake was associated with 5-year body-weight gain of 0.089kg (per 1-SD increase, 95%CI=0.072, 0.107). 3-DG was inversely associated with body-weight change (-0.076kg, -0.094, -0.058). No significant association was observed for GO (0.018kg, -0.002, 0.037). In stratified analyses, GO was associated with body-weight gain among women and older participants (above median of 52.4y). MGO was associated with higher body-weight gain among older participants. 3-DG was inversely associated with body-weight gain among younger and normal-weight participants. MGO was associated with higher risk of becoming overweight/obese, while inverse associations were observed for 3-DG. No associations were observed for GO with overweight/obesity. Dietary dicarbonyls are inconsistently associated with body-weight change among European adults. Further research is needed to clarify the role of these food components in overweight and obesity, their underlying mechanisms, and potential public-health implications.
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| 56. |
- Del Gobbo, Liana C., et al.
(författare)
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omega-3 Polyunsaturated Fatty Acid Biomarkers and Coronary Heart Disease Pooling Project of 19 Cohort Studies
- 2016
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Ingår i: JAMA Internal Medicine. - : American Medical Association (AMA). - 2168-6106 .- 2168-6114. ; 176:8, s. 1155-1166
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE The role of omega-3 polyunsaturated fatty acids for primary prevention of coronary heart disease (CHD) remains controversial. Most prior longitudinal studies evaluated self-reported consumption rather than biomarkers. OBJECTIVE To evaluate biomarkers of seafood-derived eicosapentaenoic acid (EPA; 20: 5 omega-3), docosapentaenoic acid (DPA; 22: 5 omega-3), and docosahexaenoic acid (DHA; 22: 6 omega-3) and plant-derived alpha-linolenic acid (ALA; 18: 3 omega-3) for incident CHD. DATA SOURCES A global consortium of 19 studies identified by November 2014. STUDY SELECTION Available prospective (cohort, nested case-control) or retrospective studies with circulating or tissue omega-3 biomarkers and ascertained CHD. DATA EXTRACTION AND SYNTHESIS Each study conducted standardized, individual-level analysis using harmonized models, exposures, outcomes, and covariates. Findings were centrally pooled using random-effects meta-analysis. Heterogeneity was examined by age, sex, race, diabetes, statins, aspirin, omega-6 levels, and FADS desaturase genes. MAIN OUTCOMES AND MEASURES Incident total CHD, fatal CHD, and nonfatal myocardial infarction (MI). RESULTS The 19 studies comprised 16 countries, 45 637 unique individuals, and 7973 total CHD, 2781 fatal CHD, and 7157 nonfatal MI events, with omega-3 measures in total plasma, phospholipids, cholesterol esters, and adipose tissue. Median age at baseline was 59 years (range, 18-97 years), and 28 660 (62.8%) were male. In continuous (per 1-SD increase) multivariable-adjusted analyses, the omega-3 biomarkers ALA, DPA, and DHA were associated with a lower risk of fatal CHD, with relative risks (RRs) of 0.91 (95% CI, 0.84-0.98) for ALA, 0.90 (95% CI, 0.85-0.96) for DPA, and 0.90 (95% CI, 0.84-0.96) for DHA. Although DPA was associated with a lower risk of total CHD (RR, 0.94; 95% CI, 0.90-0.99), ALA (RR, 1.00; 95% CI, 0.95-1.05), EPA (RR, 0.94; 95% CI, 0.87-1.02), and DHA (RR, 0.95; 95% CI, 0.91-1.00) were not. Significant associations with nonfatal MI were not evident. Associations appeared generally stronger in phospholipids and total plasma. Restricted cubic splines did not identify evidence of nonlinearity in dose responses. CONCLUSIONS AND RELEVANCE On the basis of available studies of free-living populations globally, biomarker concentrations of seafood and plant-derived omega-3 fatty acids are associated with a modestly lower incidence of fatal CHD.
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| 57. |
- Deschasaux, M., et al.
(författare)
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Nutritional quality of food as represented by the FSAm-NPS nutrient profiling system underlying the Nutri-Score label and cancer risk in Europe: Results from the EPIC prospective cohort study
- 2018
-
Ingår i: Plos Medicine. - : Public Library of Science (PLoS). - 1549-1676 .- 1549-1277. ; 15:9
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Tidskriftsartikel (refereegranskat)abstract
- Background Helping consumers make healthier food choices is a key issue for the prevention of cancer and other diseases. In many countries, political authorities are considering the implementation of a simplified labelling system to reflect the nutritional quality of food products. The Nutri-Score, a five-colour nutrition label, is derived from the Nutrient Profiling System of the British Food Standards Agency (modified version) (FSAm-NPS). How the consumption of foods with high/low FSAm-NPS relates to cancer risk has been studied in national/regional cohorts but has not been characterized in diverse European populations. This prospective analysis included 471,495 adults from the European Prospective Investigation into Cancer and Nutrition (EPIC, 1992-2014, median follow-up: 15.3 y), among whom there were 49,794 incident cancer cases (main locations: breast, n = 12,063; prostate, n = 6,745; colon-rectum, n = 5,806). Usual food intakes were assessed with standardized country-specific diet assessment methods. The FSAm-NPS was calculated for each food/beverage using their 100-g content in energy, sugar, saturated fatty acid, sodium, fibres, proteins, and fruits/vegetables/legumes/nuts. The FSAm-NPS scores of all food items usually consumed by a participant were averaged to obtain the individual FSAm-NPS Dietary Index (DI) scores. Multi-adjusted Cox proportional hazards models were computed. A higher FSAm-NPS DI score, reflecting a lower nutritional quality of the food consumed, was associated with a higher risk of total cancer (HRQ5 versus (Q1) = 1.07; 95% CI 1.03-1.10, P-trend < 0.001). Absolute cancer rates in those with high and low (quintiles 5 and 1) FSAm-NPS DI scores were 81.4 and 69.5 cases/10,000 person-years, respectively. Higher FSAm-NPS DI scores were specifically associated with higher risks of cancers of the colon-rectum, upper aerodigestive tract and stomach, lung for men, and liver and postmenopausal breast for women (all P < 0.05). The main study limitation is that it was based on an observational cohort using self-reported dietary data obtained through a single baseline food frequency questionnaire; thus, exposure misclassification and residual confounding cannot be ruled out. In this large multinational European cohort, the consumption of food products with a higher FSAm-NPS score (lower nutritional quality) was associated with a higher risk of cancer. This supports the relevance of the FSAm-NPS as underlying nutrient profiling system for front-of-pack nutrition labels, as well as for other public health nutritional measures.
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| 58. |
- Ding, Ming, et al.
(författare)
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Dairy consumption, systolic blood pressure, and risk of hypertension : Mendelian randomization study
- 2017
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Ingår i: The BMJ. - : BMJ Publishing Group Ltd. - 1756-1833 .- 0959-8138. ; 356
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To examine whether previous observed inverse associations of dairy intake with systolic blood pressure and risk of hypertension were causal. DESIGN Mendelian randomization study using the single nucleotide polymorphism rs4988235 related to lactase persistence as an instrumental variable. SETTING CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium. PARTICIPANTS Data from 22 studies with 171 213 participants, and an additional 10 published prospective studies with 26 119 participants included in the observational analysis. MAIN OUTCOME MEASURES The instrumental variable estimation was conducted using the ratio of coefficients approach. Using metaanalysis, an additional eight published randomized clinical trials on the association of dairy consumption with systolic blood pressure were summarized. RESULTS Compared with the CC genotype (CC is associated with complete lactase deficiency), the CT/TT genotype (TT is associated with lactose persistence, and CT is associated with certain lactase deficiency) of LCT-13910 (lactase persistence gene) rs4988235 was associated with higher dairy consumption (0.23 (about 55 g/day), 95% confidence interval 0.17 to 0.29) serving/day; P<0.001) and was not associated with systolic blood pressure (0.31, 95% confidence interval -0.05 to 0.68 mm Hg; P=0.09) or risk of hypertension (odds ratio 1.01, 95% confidence interval 0.97 to 1.05; P=0.27). Using LCT-13910 rs4988235 as the instrumental variable, genetically determined dairy consumption was not associated with systolic blood pressure (beta=1.35, 95% confidence interval -0.28 to 2.97 mm Hg for each serving/day) or risk of hypertension (odds ratio 1.04, 0.88 to 1.24). Moreover, meta-analysis of the published clinical trials showed that higher dairy intake has no significant effect on change in systolic blood pressure for interventions over one month to 12 months (intervention compared with control groups: beta=-0.21, 95% confidence interval -0.98 to 0.57 mm Hg). In observational analysis, each serving/day increase in dairy consumption was associated with -0.11 (95% confidence interval -0.20 to -0.02 mm Hg; P=0.02) lower systolic blood pressure but not risk of hypertension (odds ratio 0.98, 0.97 to 1.00; P=0.11). CONCLUSION The weak inverse association between dairy intake and systolic blood pressure in observational studies was not supported by a comprehensive instrumental variable analysis and systematic review of existing clinical trials.
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| 59. |
- Divaris, K., et al.
(författare)
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Phenotype Harmonization in the GLIDE2 Oral Health Genomics Consortium
- 2022
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Ingår i: Journal of Dental Research. - : Sage Publications. - 0022-0345 .- 1544-0591. ; 101:11, s. 1408-1416
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Tidskriftsartikel (refereegranskat)abstract
- Genetic risk factors play important roles in the etiology of oral, dental, and craniofacial diseases. Identifying the relevant risk loci and understanding their molecular biology could highlight new prevention and management avenues. Our current understanding of oral health genomics suggests that dental caries and periodontitis are polygenic diseases, and very large sample sizes and informative phenotypic measures are required to discover signals and adequately map associations across the human genome. In this article, we introduce the second wave of the Gene-Lifestyle Interactions and Dental Endpoints consortium (GLIDE2) and discuss relevant data analytics challenges, opportunities, and applications. In this phase, the consortium comprises a diverse, multiethnic sample of over 700,000 participants from 21 studies contributing clinical data on dental caries experience and periodontitis. We outline the methodological challenges of combining data from heterogeneous populations, as well as the data reduction problem in resolving detailed clinical examination records into tractable phenotypes, and describe a strategy that addresses this. Specifically, we propose a 3-tiered phenotyping approach aimed at leveraging both the large sample size in the consortium and the detailed clinical information available in some studies, wherein binary, severity-encompassing, and “precision,” data-driven clinical traits are employed. As an illustration of the use of data-driven traits across multiple cohorts, we present an application of dental caries experience data harmonization in 8 participating studies (N = 55,143) using previously developed permanent dentition tooth surface–level dental caries pattern traits. We demonstrate that these clinical patterns are transferable across multiple cohorts, have similar relative contributions within each study, and thus are prime targets for genetic interrogation in the expanded and diverse multiethnic sample of GLIDE2. We anticipate that results from GLIDE2 will decisively advance the knowledge base of mechanisms at play in oral, dental, and craniofacial health and disease and further catalyze international collaboration and data and resource sharing in genomics research.
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| 60. |
- Dodhia, Serena A., et al.
(författare)
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Examining the causal association between 25-hydroxyvitamin D and caries in children and adults : A two-sample Mendelian randomization approach
- 2021
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Ingår i: Wellcome Open Research. - : F1000 Research Ltd. - 2398-502X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Prior observational studies have reported that higher levels of vitamin D are associated with decreased caries risk in children. However, these studies are prone to bias and confounding so do not provide causal inference. Genetic variants associated with a risk factor of interest can be used as proxies, in a Mendelian randomization (MR) analysis, to test for causal association with an outcome. The objective was to estimate the causal association between serum 25-hydroxyvitamin D (25(OH)D) (the commonly measured vitamin D metabolite in blood) and dental caries using a two-sample MR approach which estimates the causal effect of an exposure on an outcome.Methods: A total of 79 genetic variants reliably associated with 25(OH)D were identified from genome-wide association studies and used as a proxy measure of 25(OH)D. The association of this proxy measure with three outcome measures was tested; specifically: caries in primary teeth (n=17,035, aged 3-12 years), caries in permanent teeth in childhood and adolescence (n=13,386, aged 6-18 years), and caries severity in adulthood proxied by decayed, missing and filled tooth surfaces (DMFS) counts (n=26,792, aged 18-93 years).Results: The estimated causal effect of a one standard deviation increase in natural log-transformed 25(OH)D could be summarized as an odds ratio of 1.06 (95%CI: 0.81, 1.31; P=0.66) for caries in primary teeth and 1.00 (95%CI: 0.76, 1.23; P=0.97) for caries in permanent teeth in childhood and adolescence. In adults, the estimated casual effect of a one standard deviation increase in natural log-transformed 25(OH)D was 0.31 fewer affected tooth surfaces (95%CI: from 1.81 fewer DMFS to 1.19 more DMFS; P=0.68)Conclusions: The MR-derived effect estimates for these three measures are small in magnitude with wide confidence intervals and do not provide evidence for a causal relationship between 25(OH)D and dental caries.
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