Publications by authors named "Alexandra Nieters"

166 Publications

Initial presenting manifestations in 16,486 patients with inborn errors of immunity include infections and noninfectious manifestations.

J Allergy Clin Immunol 2021 Apr 23. Epub 2021 Apr 23.

Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; CIBSS - Centre for Integrative Biological Signalling Studies, Albert-Ludwigs University, Freiburg, Germany. Electronic address:

Background: Inborn errors of immunity (IEI) are rare diseases, which makes diagnosis a challenge. A better description of the initial presenting manifestations should improve awareness and avoid diagnostic delay. Although increased infection susceptibility is a well-known initial IEI manifestation, less is known about the frequency of other presenting manifestations.

Objective: We sought to analyze age-related initial presenting manifestations of IEI including different IEI disease cohorts.

Methods: We analyzed data on 16,486 patients of the European Society for Immunodeficiencies Registry. Patients with autoinflammatory diseases were excluded because of the limited number registered.

Results: Overall, 68% of patients initially presented with infections only, 9% with immune dysregulation only, and 9% with a combination of both. Syndromic features were the presenting feature in 12%, 4% had laboratory abnormalities only, 1.5% were diagnosed because of family history only, and 0.8% presented with malignancy. Two-third of patients with IEI presented before the age of 6 years, but a quarter of patients developed initial symptoms only as adults. Immune dysregulation was most frequently recognized as an initial IEI manifestation between age 6 and 25 years, with male predominance until age 10 years, shifting to female predominance after age 40 years. Infections were most prevalent as a first manifestation in patients presenting after age 30 years.

Conclusions: An exclusive focus on infection-centered warning signs would have missed around 25% of patients with IEI who initially present with other manifestations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaci.2021.04.015DOI Listing
April 2021

Altered Spectrum of Lymphoid Neoplasms in a Single-Center Cohort of Common Variable Immunodeficiency with Immune Dysregulation.

J Clin Immunol 2021 Aug 19;41(6):1250-1265. Epub 2021 Apr 19.

University of Freiburg, Freiburg, Germany.

Purpose: Common variable immune deficiency (CVID) confers an increased risk of lymphoid neoplasms, but reports describing the precise WHO specification of the lymphoma subtypes and their immunological environment are lacking. We therefore classified lymphomas-occurring in a cohort of 21 adult CVID patients during a 17-year period at our center-according to the 2016 WHO classification and characterized the local and systemic immunological context RESULTS: The median time between the onset of CVID and lymphoma was 14 years. Patients showed a high prevalence of preceding immune dysregulation: lymphadenopathy (n = 13, 62%), splenomegaly (n = 18, 86%), autoimmune cytopenia (n = 14, 67%), and gastrointestinal involvement (n = 15, 71%). The entities comprised extranodal marginal zone lymphoma (n = 6), diffuse large B cell lymphoma (n = 7), plasmablastic lymphoma (n = 1), classic Hodgkin lymphoma (n = 4, including three cases with germline CTLA4 mutations), T cell large granular lymphocytic leukemia (n = 2), and peripheral T cell lymphoma, not otherwise specified (n = 1), but no follicular lymphoma. An Epstein-Barr virus association was documented in eight of 16 investigated lymphomas. High expression of PDL1 by tumor cells in five and of PDL1 and PD1 by tumor-infiltrating macrophages and T cells in 12 of 12 investigated lymphomas suggested a tolerogenic immunological tumor environment.

Conclusion: In summary, a diverse combination of specific factors like genetic background, chronic immune activation, viral trigger, and impaired immune surveillance contributes to the observed spectrum of lymphomas in CVID. In the future, targeted therapies, e.g., PD1/PDL1 inhibitors in CVID associated lymphomas with a tolerogenic environment may improve therapy outcome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10875-021-01016-4DOI Listing
August 2021

Red Blood Cell Fatty Acids and Risk of Colorectal Cancer in The European Prospective Investigation into Cancer and Nutrition (EPIC).

Cancer Epidemiol Biomarkers Prev 2021 May 22;30(5):874-885. Epub 2021 Feb 22.

Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.

Background: A growing body of evidence suggests that alterations of dietary fatty acid (FA) profiles are associated with colorectal cancer risk. However, data from large-scale epidemiologic studies using circulating FA measurements to objectively assess individual FA and FA categories are scarce.

Methods: We investigate the association between red blood cell (RBC) membrane FAs and risk of colorectal cancer in a case-control study nested within a large prospective cohort. After a median follow-up of 6.4 years, 1,069 incident colorectal cancer cases were identified and matched to 1,069 controls among participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). The FA composition of RBC phospholipids (in mol%) was analyzed by gas chromatography, and their association with risk of colorectal cancer was estimated by multivariable adjusted conditional logistic regression models.

Results: After correction for multiple testing, subjects with higher concentrations of RBC stearic acid were at higher risk for colorectal cancer (OR = 1.23; 95% CI = 1.07-1.42, per 1 mol%). Conversely, colorectal cancer incidence decreased with increasing proportions of RBC n-3 PUFA, particularly eicosapentaenoic acid (0.75; 0.62-0.92, per 1 mol%). The findings for the n-6 PUFA arachidonic acid were inconsistent.

Conclusions: The positive association between prediagnostic RBC stearic acid and colorectal cancer reflects putative differences in FA intake and metabolism between cancer cases and matched controls, which deserve further investigation. The inverse relationship between EPA and colorectal cancer is in line with the repeatedly reported protective effect of fish consumption on colorectal cancer risk.

Impact: These findings add to the evidence on colorectal cancer prevention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1055-9965.EPI-20-1426DOI Listing
May 2021

Parathyroid Hormone in Pregnancy: Vitamin D and Other Determinants.

Nutrients 2021 Jan 25;13(2). Epub 2021 Jan 25.

Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Hirschengraben 84, 8001 Zurich, Switzerland.

We aimed to assess the parathyroid hormone (PTH) concentration in pregnant women at the beginning of pregnancy (1st trimester) and within days before delivery (3rd trimester) and evaluate its determinants. From September 2014 through December 2015 in a cross-sectional study, 204 women in the 1st trimester of pregnancy and 203 women in the 3rd trimester of pregnancy were recruited. Blood samples were collected to measure PTH and circulating 25-hydroxy-vitamin D (25(OH)D) concentrations. Lifestyle and demographic data were collected using a questionnaire. Serum 25(OH)D and PTH were inversely correlated in both early and late pregnancy. Our analyses suggest that in the 3rd trimester of pregnancy, a 25(OH)D level of 18.9 ng/mL (47.3 nmol/L) could serve as an inflection point for the maximal suppression of PTH. Statistically significant determinants of PTH concentrations in multiple regression were 25(OH)D concentrations, season, multiparity and education of the partner (all < 0.05) in early pregnancy. In late pregnancy, 25(OH)D concentrations and country of origin were statistically significant determinants of PTH concentrations (all < 0.05). These factors and their effect on PTH appear to be vastly determined by 25(OH)D; however, they might also affect PTH through other mechanisms besides 25(OH)D.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu13020360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911996PMC
January 2021

Characterization of pre-existing and induced SARS-CoV-2-specific CD8 T cells.

Nat Med 2021 01 12;27(1):78-85. Epub 2020 Nov 12.

Department of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Emerging data indicate that SARS-CoV-2-specific CD8 T cells targeting different viral proteins are detectable in up to 70% of convalescent individuals. However, very little information is currently available about the abundance, phenotype, functional capacity and fate of pre-existing and induced SARS-CoV-2-specific CD8 T cell responses during the natural course of SARS-CoV-2 infection. Here, we define a set of optimal and dominant SARS-CoV-2-specific CD8 T cell epitopes. We also perform a high-resolution ex vivo analysis of pre-existing and induced SARS-CoV-2-specific CD8 T cells, applying peptide-loaded major histocompatibility complex class I (pMHCI) tetramer technology. We observe rapid induction, prolonged contraction and emergence of heterogeneous and functionally competent cross-reactive and induced memory CD8 T cell responses in cross-sectionally analyzed individuals with mild disease following SARS-CoV-2 infection and three individuals longitudinally assessed for their T cells pre- and post-SARS-CoV-2 infection. SARS-CoV-2-specific memory CD8 T cells exhibited functional characteristics comparable to influenza-specific CD8 T cells and were detectable in SARS-CoV-2 convalescent individuals who were seronegative for anti-SARS-CoV-2 antibodies targeting spike (S) and nucleoprotein (N). These results define cross-reactive and induced SARS-CoV-2-specific CD8 T cell responses as potentially important determinants of immune protection in mild SARS-CoV-2 infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-020-01143-2DOI Listing
January 2021

Association between anthropometry and lifestyle factors and risk of B-cell lymphoma: An exposome-wide analysis.

Int J Cancer 2021 May 12;148(9):2115-2128. Epub 2020 Nov 12.

Department of Oncology, Lund University, Lund, Sweden.

To better understand the role of individual and lifestyle factors in human disease, an exposome-wide association study was performed to investigate within a single-study anthropometry measures and lifestyle factors previously associated with B-cell lymphoma (BCL). Within the European Prospective Investigation into Cancer and nutrition study, 2402 incident BCL cases were diagnosed from 475 426 participants that were followed-up on average 14 years. Standard and penalized Cox regression models as well as principal component analysis (PCA) were used to evaluate 84 exposures in relation to BCL risk. Standard and penalized Cox regression models showed a positive association between anthropometric measures and BCL and multiple myeloma/plasma cell neoplasm (MM). The penalized Cox models additionally showed the association between several exposures from categories of physical activity, smoking status, medical history, socioeconomic position, diet and BCL and/or the subtypes. PCAs confirmed the individual associations but also showed additional observations. The PC5 including anthropometry, was positively associated with BCL, diffuse large B-cell lymphoma (DLBCL) and MM. There was a significant positive association between consumption of sugar and confectionary (PC11) and follicular lymphoma risk, and an inverse association between fish and shellfish and Vitamin D (PC15) and DLBCL risk. The PC1 including features of the Mediterranean diet and diet with lower inflammatory score showed an inverse association with BCL risk, while the PC7, including dairy, was positively associated with BCL and DLBCL risk. Physical activity (PC10) was positively associated with DLBCL risk among women. This study provided informative insights on the etiology of BCL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.33369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048490PMC
May 2021

Occupational exposure to organic dust and risk of lymphoma subtypes in the EPILYMPH case-control study.

Scand J Work Environ Health 2021 Jan 25;47(1):42-51. Epub 2020 Sep 25.

Department of Medical Sciences and Public Health, Occupational Medicine unit, University of Cagliari, Monserrato (Cagliari) Italy.

Objectives This study aimed to estimate the risk of lymphoma and its major subtypes in relation to occupational exposure to specific organic dusts. Methods We explored the association in 1853 cases and 1997 controls who participated in the EpiLymph case-control study, conducted in six European countries in 1998-2004. Based on expert assessment of lifetime occupational exposures, we calculated the risk of the major lymphoma subtypes associated with exposure to six specific organic dusts, namely, flour, hardwood, softwood, natural textile, synthetic textile, and leather, and two generic (any types) groups: wood and textile dusts. Risk was predicted with unconditional regression modeling, adjusted by age, gender, study center, and education. Results We observed a 2.1-fold increase in risk of follicular lymphoma associated with ever exposure to leather dust [95% confidence interval (CI) 1.01-4.20]. After excluding subjects who ever worked in a farm or had ever been exposed to solvents, risk of B-cell lymphoma was elevated in relation to ever exposure to leather dust [odd ratio (OR) 2.2, 95% CI 1.00-4.78], but it was not supported by increasing trends with the exposure metrics. Risk of Hodgkin lymphoma was elevated (OR 2.0, 95% CI 0.95-4.30) for exposure to textile dust, with consistent upward trends by cumulative exposure and three independent exposure metrics combined (P=0.023, and P=0.0068, respectively). Conclusions Future, larger studies might provide further insights into the nature of the association we observed between exposure to textile dust and risk of Hodgkin lymphoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5271/sjweh.3925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801142PMC
January 2021

Enabling External Inquiries to an Existing Patient Registry by Using the Open Source Registry System for Rare Diseases: Demonstration of the System Using the European Society for Immunodeficiencies Registry.

JMIR Med Inform 2020 Oct 7;8(10):e17420. Epub 2020 Oct 7.

Medical Informatics Group, University Hospital Frankfurt, Frankfurt am Main, Germany.

Background: The German Network on Primary Immunodeficiency Diseases (PID-NET) utilizes the European Society for Immunodeficiencies (ESID) registry as a platform for collecting data. In the context of PID-NET data, we show how registries based on custom software can be made interoperable for better collaborative access to precollected data. The Open Source Registry System for Rare Diseases (Open-Source-Registersystem für Seltene Erkrankungen [OSSE], in German) provides patient organizations, physicians, scientists, and other parties with open source software for the creation of patient registries. In addition, the necessary interoperability between different registries based on the OSSE, as well as existing registries, is supported, which allows those registries to be confederated at both the national and international levels.

Objective: Data from the PID-NET registry should be made available in an interoperable manner without losing data sovereignty by extending the existing custom software of the registry using the OSSE registry framework.

Methods: This paper describes the following: (1) the installation and configuration of the OSSE bridgehead, (2) an approach using a free toolchain to set up the required interfaces to connect a registry with the OSSE bridgehead, and (3) the decentralized search, which allows the formulation of inquiries that are sent to a selected set of registries of interest.

Results: PID-NET uses the established and highly customized ESID registry software. By setting up a so-called OSSE bridgehead, PID-NET data are made interoperable according to a federated approach, and centrally formulated inquiries for data can be received. As the first registry to use the OSSE bridgehead, the authors introduce an approach using a free toolchain to efficiently implement and maintain the required interfaces. Finally, to test and demonstrate the system, two inquiries are realized using the graphical query builder. By establishing and interconnecting an OSSE bridgehead with the underlying ESID registry, confederated queries for data can be received and, if desired, the inquirer can be contacted to further discuss any requirements for cooperation.

Conclusions: The OSSE offers an infrastructure that provides the possibility of more collaborative and transparent research. The decentralized search functionality includes registries into one search application while still maintaining data sovereignty. The OSSE bridgehead enables any registry software to be integrated into the OSSE network. The proposed toolchain to set up the required interfaces consists of freely available software components that are well documented. The use of the decentralized search is uncomplicated to use and offers a well-structured, yet still improvable, graphical user interface to formulate queries.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2196/17420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578818PMC
October 2020

Covid-19 in patients with hematological and solid cancers at a Comprehensive Cancer Center in Germany.

Cancer Med 2020 11 15;9(22):8412-8422. Epub 2020 Sep 15.

Department of Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.

Background: Patients with cancer are considered a high-risk group for viral pneumonia, with an increased probability of fatal outcome. Here, we investigated the clinical characteristics and outcome of patients with solid and hematological cancers and concomitant Covid-19 at a Comprehensive Cancer Center in a Covid-19 hotspot area in Germany.

Methods: We performed a retrospective single center cohort study of 39 patients with hematological and solid cancers who were hospitalized at the University Hospital Freiburg for Covid-19. Using univariate and multivariate Cox regression models we compared time to severe events and overall survival to an age-matched control cohort of 39 patients with confirmed Covid-19 without a cancer diagnosis.

Results: In the cancer cohort 29 patients had a diagnosis of a solid tumor, and 10 had a hematological malignancy. In total, eight patients (21%) in the cancer and 14 patients (36%) from the noncancer cohort died during the observation period. Presence of a malignancy was not significantly associated with survival or time to occurrence of severe events. Major influences on mortality were high IL-6 levels at Covid-19 diagnosis (HR = 6.95, P = .0121) and age ≥ 65 years (HR = 6.22, P = .0156).

Conclusions: Compared to an age-matched noncancer cohort, we did not observe an association between a cancer diagnosis and a more severe disease course or higher fatality rate in patients with Covid-19. Patients with a hematological malignancy showed a trend towards a longer duration until clinical improvement and longer hospitalization time compared to patients with a solid cancer. Cancer per se does not seem to be a confounder for dismal outcome in Covid-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cam4.3460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666742PMC
November 2020

Mediating effect of soluble B-cell activation immune markers on the association between anthropometric and lifestyle factors and lymphoma development.

Sci Rep 2020 08 14;10(1):13814. Epub 2020 Aug 14.

Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Utrecht University, P.O. Box 80178, 3508 TD, Utrecht, The Netherlands.

Sustained B-cell activation is an important mechanism contributing to B-cell lymphoma (BCL). We aimed to validate four previously reported B-cell activation markers predictive of BCL risk (sCD23, sCD27, sCD30, and CXCL13) and to examine their possible mediating effects on the association between anthropometric and lifestyle factors and major BCL subtypes. Pre-diagnostic serum levels were measured for 517 BCL cases and 525 controls in a nested case-control study. The odds ratios of BCL were 6.2 in the highest versus lowest quartile for sCD23, 2.6 for sCD30, 4.2 for sCD27, and 2.6 for CXCL13. Higher levels of all markers were associated with increased risk of chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL). Following mutual adjustment for the other immune markers, sCD23 remained associated with all subtypes and CXCL13 with FL and DLBCL. The associations of sCD23 with CLL and DLBCL and CXCL13 with DLBCL persisted among cases sampled > 9 years before diagnosis. sCD23 showed a good predictive ability (area under the curve = 0.80) for CLL, in particular among older, male participants. sCD23 and CXCL13 showed a mediating effect between body mass index (positive) and DLBCL risk, while CXCL13 contributed to the association between physical activity (inverse) and DLBCL. Our data suggest a role of B-cell activation in BCL development and a mediating role of the immune system for lifestyle factors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-70790-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429856PMC
August 2020

Association of ionizing radiation dose from common medical diagnostic procedures and lymphoma risk in the Epilymph case-control study.

PLoS One 2020 10;15(7):e0235658. Epub 2020 Jul 10.

CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.

Medical diagnostic X-rays are an important source of ionizing radiation (IR) exposure in the general population; however, it is unclear if the resulting low patient doses increase lymphoma risk. We examined the association between lifetime medical diagnostic X-ray dose and lymphoma risk, taking into account potential confounding factors, including medical history. The international Epilymph study (conducted in the Czech-Republic, France, Germany, Ireland, Italy, and Spain) collected self-reported information on common diagnostic X-ray procedures from 2,362 lymphoma cases and 2,465 frequency-matched (age, sex, country) controls. Individual lifetime cumulative bone marrow (BM) dose was estimated using time period-based dose estimates for different procedures and body parts. The association between categories of BM dose and lymphoma risk was examined using unconditional logistic regression models adjusting for matching factors, socioeconomic variables, and the presence of underlying medical conditions (atopic, autoimmune, infectious diseases, osteoarthritis, having had a sick childhood, and family history of lymphoma) as potential confounders of the association. Cumulative BM dose was low (median 2.25 mGy) and was not positively associated with lymphoma risk. Odds ratios (ORs) were consistently less than 1.0 in all dose categories compared to the reference category (less than 1 mGy). Results were similar after adjustment for potential confounding factors, when using different exposure scenarios, and in analyses by lymphoma subtype and by type of control (hospital-, population-based). Overall no increased risk of lymphoma was observed. The reduced ORs may be related to unmeasured confounding or other sources of systematic bias.We found little evidence that chronic medical conditions confound lymphoma risk and medical radiation associations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235658PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351167PMC
September 2020

Occupational exposure to ionizing radiation and risk of lymphoma subtypes: results of the Epilymph European case-control study.

Environ Health 2020 04 25;19(1):43. Epub 2020 Apr 25.

Department of Medical Sciences and Public Health, University of Cagliari, SS554, km 4.500, 09042, Monserrato (Cagliari), Italy.

Background: Evidence linking risk of lymphoma and B-cell lymphoma subtypes to ionizing radiation is inconclusive, particularly at low exposure levels.

Methods: We investigated risk of lymphoma (all subtypes), B-cell lymphomas, and its major subtypes, associated with low-level occupational exposure to ionizing radiation, in 2346 lymphoma cases and 2463 controls, who participated in the multicenter EpiLymph case-control study. We developed a job-exposure matrix to estimate exposure to ionizing radiation, distinguishing between internal and external radiation, and we applied it to the lifetime occupational history of study subjects, We calculated the Odds Ratio (OR) and its 95% confidence interval (95% CI) for lymphoma (all subtypes combined), B-cell lymphoma, and its major subtypes using unconditional, polytomous logistic regression adjusting for age, gender, and education.

Results: We did not observe an association between exposure metrics of external and internal radiation and risk of lymphoma (all subtypes), nor with B-cell lymphoma, or its major subtypes, at the levels regularly experienced in occupational settings. An elevated risk of diffuse large B cell lymphoma was observed among the most likely exposed study subjects with relatively higher exposure intensity, which would be worth further investigation.

Conclusions: Further investigation is warranted on risk of B cell lymphoma subtypes associated with low-level occupational exposure to external ionizing radiation, and to clarify whether lymphoma should be included among the cancer outcomes related to ionizing radiation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12940-020-00596-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183712PMC
April 2020

Correction to: Infectious mononucleosis, immune genotypes, and non-Hodgkin lymphoma (NHL): an InterLymph Consortium study.

Cancer Causes Control 2020 06;31(6):607

Department of Preventive Medicine, Center for Genetic Epidemiology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

Unfortunately, the word "Group" is missed in the article title of the original publication. It has been corrected by this erratum.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10552-020-01297-xDOI Listing
June 2020

[Self-reported infections in the German National Cohort (GNC) in the context of the current research landscape].

Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2020 Apr;63(4):404-414

Abteilung Epidemiologie von Krebserkrankungen, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Deutschland.

Background: Infectious diseases continue to play an important role for disease perception, health-economic considerations and public health in Germany. In recent years, infectious diseases have been linked to the development of non-communicable diseases. Analyses of the German National Cohort (GNC) may provide deeper insights into this issue and pave the way for new targeted approaches in disease prevention.

Objectives: The aim was to describe the tools used to assess infectious diseases and to present initial data on infectious disease frequencies, as well as to relate the GNC assessment tools to data collection methods in other studies in Germany.

Methods: As part of the baseline examination, questions regarding infectious diseases were administered using both an interview and a self-administered touchscreen questionnaire. Data from the initial 101,787 GNC participants were analysed.

Results: In the interview, 0.2% (HIV/AIDS) to 8.6% (shingles) of respondents reported ever having a medical diagnosis of shingles, postherpetic neuralgia (in cases where shingles was reported), hepatitis B/C, HIV/AIDS, tuberculosis or sepsis if treated in hospital. In the questionnaire, 12% (cystitis) to 81% (upper respiratory tract infections) of respondents reported having experienced at least one occurrence of upper or lower respiratory tract infections, gastrointestinal infections, cystitis or fever within the past 12 months.

Outlook: The cross-sectional analyses of data and tools presented here - for example on determinants of susceptibility to self-reported infections - can be anticipated from the year 2021 onward. Beyond that, more extensive research into infectious disease epidemiology will follow, particularly once analyses of GNC biological materials have been performed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00103-020-03114-xDOI Listing
April 2020

Healthy lifestyle and the risk of lymphoma in the European Prospective Investigation into Cancer and Nutrition study.

Int J Cancer 2020 09 30;147(6):1649-1656. Epub 2020 Mar 30.

Department of Radiation Sciences and Oncology, Umeå University, Umeå, Sweden.

Limited evidence exists on the role of modifiable lifestyle factors on the risk of lymphoma. In this work, the associations between adherence to healthy lifestyles and risks of Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) were evaluated in a large-scale European prospective cohort. Within the European Prospective Investigation into Cancer and Nutrition (EPIC), 2,999 incident lymphoma cases (132 HL and 2,746 NHL) were diagnosed among 453,808 participants after 15 years (median) of follow-up. The healthy lifestyle index (HLI) score combined information on smoking, alcohol intake, diet, physical activity and BMI, with large values of HLI expressing adherence to healthy behavior. Cox proportional hazards models were used to estimate lymphoma hazard ratios (HR) and 95% confidence interval (CI). Sensitivity analyses were conducted by excluding, in turn, each lifestyle factor from the HLI score. The HLI was inversely associated with HL, with HR for a 1-standard deviation (SD) increment in the score equal to 0.78 (95% CI: 0.66, 0.94). Sensitivity analyses showed that the association was mainly driven by smoking and marginally by diet. NHL risk was not associated with the HLI, with HRs for a 1-SD increment equal to 0.99 (0.95, 1.03), with no evidence for heterogeneity in the association across NHL subtypes. In the EPIC study, adherence to healthy lifestyles was not associated with overall lymphoma or NHL risk, while an inverse association was observed for HL, although this was largely attributable to smoking. These findings suggest a limited role of lifestyle factors in the etiology of lymphoma subtypes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.32977DOI Listing
September 2020

Infectious mononucleosis, immune genotypes, and non-Hodgkin lymphoma (NHL): an InterLymph Consortium study.

Cancer Causes Control 2020 05 2;31(5):451-462. Epub 2020 Mar 2.

Department of Preventive Medicine, Center for Genetic Epidemiology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

Purpose: We explored the interaction between non-Hodgkin lymphoma (NHL), infectious mononucleosis (IM) history, and immune-related genotypes in a pooled case-control analysis.

Methods: A total of 7,926 NHL patients and 10,018 controls from 12 case-control studies were included. Studies were conducted during various time periods between 1988 and 2008, and participants were 17-96 years of age at the time of ascertainment/recruitment. Self-reported IM history and immune response genotypes were provided by the InterLymph Data Coordinating Center at Mayo Clinic. Odds ratios (OR) were estimated using multivariate logistic regression, and interactions were estimated using the empirical Bayes method. P was used to account for multiple comparisons.

Results: There was evidence of an interaction effect between IM history and two variants on T-cell lymphoma (TCL) risk: rs1143627 in interleukin-1B (IL1B) (p = 0.04, OR = 0.09, 95% confidence interval [CI] 0.01, 0.87) and rs1800797 in interleukin-6 (IL6) (p = 0.03, OR = 0.08, 95% CI 0.01, 0.80). Neither interaction effect withstood adjustment for multiple comparisons. There were no statistically significant interactions between immune response genotypes and IM on other NHL subtypes.

Conclusions: Genetic risk variants in IL1B and IL6 may affect the association between IM and TCL, possibly by influencing T-cell activation, growth, and differentiation in the presence of IM, thereby decreasing risk of immune cell proliferation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10552-020-01266-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7534692PMC
May 2020

Lipid Trait Variants and the Risk of Non-Hodgkin Lymphoma Subtypes: A Mendelian Randomization Study.

Cancer Epidemiol Biomarkers Prev 2020 05 27;29(5):1074-1078. Epub 2020 Feb 27.

Emory University, Atlanta, Georgia.

Background: Lipid traits have been inconsistently linked to risk of non-Hodgkin lymphoma (NHL). We examined the association of genetically predicted lipid traits with risk of diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), and marginal zone lymphoma (MZL) using Mendelian randomization (MR) analysis.

Methods: Genome-wide association study data from the InterLymph Consortium were available for 2,661 DLBCLs, 2,179 CLLs, 2,142 FLs, 824 MZLs, and 6,221 controls. SNPs associated ( < 5 × 10) with high-density lipoprotein (HDL, = 164), low-density lipoprotein (LDL, = 137), total cholesterol (TC, = 161), and triglycerides (TG, = 123) were used as instrumental variables (IV), explaining 14.6%, 27.7%, 16.8%, and 12.8% of phenotypic variation, respectively. Associations between each lipid trait and NHL subtype were calculated using the MR inverse variance-weighted method, estimating odds ratios (OR) per standard deviation and 95% confidence intervals (CI).

Results: HDL was positively associated with DLBCL (OR = 1.14; 95% CI, 1.00-1.30) and MZL (OR = 1.09; 95% CI, 1.01-1.18), while TG was inversely associated with MZL risk (OR = 0.90; 95% CI, 0.83-0.99), all at nominal significance ( < 0.05). A positive trend was observed for HDL with FL risk (OR = 1.08; 95% CI, 0.99-1.19; = 0.087). No associations were noteworthy after adjusting for multiple testing.

Conclusions: We did not find evidence of a clear or strong association of these lipid traits with the most common NHL subtypes. While these IVs have been previously linked to other cancers, our findings do not support any causal associations with these NHL subtypes.

Impact: Our results suggest that prior reported inverse associations of lipid traits are not likely to be causal and could represent reverse causality or confounding.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1055-9965.EPI-19-0803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196490PMC
May 2020

Risk Factors for Complicated Lymphadenitis Caused by Nontuberculous Mycobacteria in Children.

Emerg Infect Dis 2020 03;26(3):579-586

Nontuberculous mycobacteria (NTM) are an emerging cause of infections, including chronic lymphadenitis in children. To identify risk factors for NTM lymphadenitis, particularly complicated disease, we collected epidemiologic, clinical, and microbiological data on 138 cases of NTM lymphadenitis in children across 13 centers in Germany and Austria. We assessed lifestyle factors but did not identify specific risk behaviors. We noted that more cases of NTM lymphadenitis occurred during cold months than during warm months. Moreover, we noted female sex and age <5.5 years as potential risk factors. Complete extirpation of the affected lymph node appeared to be the best therapeutic measure. We integrated the study data to develop a simple risk score to predict unfavorable clinical outcomes for NTM lymphadenitis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3201/eid2603.191388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7045849PMC
March 2020

Genetically Determined Height and Risk of Non-hodgkin Lymphoma.

Front Oncol 2019 28;9:1539. Epub 2020 Jan 28.

Interdisciplinary Department of Medicine, University of Bari, Bari, Italy.

Although the evidence is not consistent, epidemiologic studies have suggested that taller adult height may be associated with an increased risk of some non-Hodgkin lymphoma (NHL) subtypes. Height is largely determined by genetic factors, but how these genetic factors may contribute to NHL risk is unknown. We investigated the relationship between genetic determinants of height and NHL risk using data from eight genome-wide association studies (GWAS) comprising 10,629 NHL cases, including 3,857 diffuse large B-cell lymphoma (DLBCL), 2,847 follicular lymphoma (FL), 3,100 chronic lymphocytic leukemia (CLL), and 825 marginal zone lymphoma (MZL) cases, and 9,505 controls of European ancestry. We evaluated genetically predicted height by constructing polygenic risk scores using 833 height-associated SNPs. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for association between genetically determined height and the risk of four NHL subtypes in each GWAS and then used fixed-effect meta-analysis to combine subtype results across studies. We found suggestive evidence between taller genetically determined height and increased CLL risk (OR = 1.08, 95% CI = 1.00-1.17, = 0.049), which was slightly stronger among women (OR = 1.15, 95% CI: 1.01-1.31, = 0.036). No significant associations were observed with DLBCL, FL, or MZL. Our findings suggest that there may be some shared genetic factors between CLL and height, but other endogenous or environmental factors may underlie reported epidemiologic height associations with other subtypes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2019.01539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6999122PMC
January 2020

Serum levels of hsa-miR-16-5p, hsa-miR-29a-3p, hsa-miR-150-5p, hsa-miR-155-5p and hsa-miR-223-3p and subsequent risk of chronic lymphocytic leukemia in the EPIC study.

Int J Cancer 2020 09 2;147(5):1315-1324. Epub 2020 Mar 2.

Centro de Investigación Biomédica en Red: Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.

Chronic lymphocytic leukemia (CLL) is an incurable disease accounting for almost one-third of leukemias in the Western world. Aberrant expression of microRNAs (miRNAs) is a well-established characteristic of CLL, and the robust nature of miRNAs makes them eminently suitable liquid biopsy biomarkers. Using a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC), the predictive values of five promising human miRNAs (hsa-miR-16-5p, hsa-miR-29a-3p, hsa-miR-150-5p, hsa-miR-155-5p and hsa-miR-223-3p), identified in a pilot study, were examined in serum of 224 CLL cases (diagnosed 3 months to 18 years after enrollment) and 224 matched controls using Taqman based assays. Conditional logistic regressions were applied to adjust for potential confounders. The median time from blood collection to CLL diagnosis was 10 years (p25-p75: 7-13 years). Overall, the upregulation of hsa-miR-150-5p, hsa-miR-155-5p and hsa-miR-29a-3p was associated with subsequent risk of CLL [OR (95%CI) = 1.42 (1.18-1.72), 1.64 (1.31-2.04) and 1.75 (1.31-2.34) for hsa-miR-150-5p, hsa-miR-155-5p and hsa-miR-29a-3p, respectively] and the strongest associations were observed within 10 years of diagnosis. However, the predictive performance of these miRNAs was modest (area under the curve <0.62). hsa-miR-16-5p and hsa-miR-223-3p levels were unrelated to CLL risk. The findings of this first prospective study suggest that hsa-miR-29a, hsa-miR-150-5p and hsa-miR-155-5p were upregulated in early stages of CLL but were modest predictive biomarkers of CLL risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.32894DOI Listing
September 2020

[Development of an Intervention to Enhance Health Literacy of Patients with Common Variable Immunodeficiency (CVID)].

Gesundheitswesen 2021 Mar 15;83(3):195-197. Epub 2019 Oct 15.

Medizinische Fakultät, Zentrum für Chronische Immundefizienz (CCI), Albert-Ludwigs-Universität Freiburg, Freiburg.

Objective: The aim of the article was to describe the development of a training program to enhance the health literacy of patients with immunodeficiency. In addition, patient satisfaction and acceptance of the training will be evaluated.

Methods: Patients' needs were identified with a questionnaire (N=238). Additionally, interviews with clinical immunologists (N=5) and patients with common variable immunodeficiency (CVID) (N=9) were conducted. On this basis, the authors developed a manual for the intervention. It focuses on active communication with physicians as well as health-related communication at the workplace. The evaluation of patient satisfaction with the intervention was based on a questionnaire (N=49).

Results: The results show that the ratings of the patients were in the good to very good range (M=1.77; SD=0.38). From the analysis of the free text, hints for training improvement could be derived.

Conclusion: Evaluation of the intervention showed that the new training was accepted and patients considered it comprehensible and relevant.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/a-1005-7235DOI Listing
March 2021

Inherited variants at 3q13.33 and 3p24.1 are associated with risk of diffuse large B-cell lymphoma and implicate immune pathways.

Hum Mol Genet 2020 01;29(1):70-79

Memorial Sloan-Kettering Cancer Center, New York, NY, USA.

We previously identified five single nucleotide polymorphisms (SNPs) at four susceptibility loci for diffuse large B-cell lymphoma (DLBCL) in individuals of European ancestry through a large genome-wide association study (GWAS). To further elucidate genetic susceptibility to DLBCL, we sought to validate two loci at 3q13.33 and 3p24.1 that were suggestive in the original GWAS with additional genotyping. In the meta-analysis (5662 cases and 9237 controls) of the four original GWAS discovery scans and three replication studies, the 3q13.33 locus (rs9831894; minor allele frequency [MAF] = 0.40) was associated with DLBCL risk [odds ratio (OR) = 0.83, P = 3.62 × 10-13]. rs9831894 is in linkage disequilibrium (LD) with additional variants that are part of a super-enhancer that physically interacts with promoters of CD86 and ILDR1. In the meta-analysis (5510 cases and 12 817 controls) of the four GWAS discovery scans and four replication studies, the 3p24.1 locus (rs6773363; MAF = 0.45) was also associated with DLBCL risk (OR = 1.20, P = 2.31 × 10-12). This SNP is 29 426-bp upstream of the nearest gene EOMES and in LD with additional SNPs that are part of a highly lineage-specific and tumor-acquired super-enhancer that shows long-range interaction with AZI2 promoter. These loci provide additional evidence for the role of immune function in the etiology of DLBCL, the most common lymphoma subtype.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/hmg/ddz228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001601PMC
January 2020

Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes.

Genet Epidemiol 2019 10 13;43(7):844-863. Epub 2019 Aug 13.

Medicina Traslazionale, Università del Piemonte Orientale, Vercelli, Italy.

Epidemiologic studies show an increased risk of non-Hodgkin lymphoma (NHL) in patients with autoimmune disease (AD), due to a combination of shared environmental factors and/or genetic factors, or a causative cascade: chronic inflammation/antigen-stimulation in one disease leads to another. Here we assess shared genetic risk in genome-wide-association-studies (GWAS). Secondary analysis of GWAS of NHL subtypes (chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and marginal zone lymphoma) and ADs (rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis). Shared genetic risk was assessed by (a) description of regional genetic of overlap, (b) polygenic risk score (PRS), (c)"diseasome", (d)meta-analysis. Descriptive analysis revealed few shared genetic factors between each AD and each NHL subtype. The PRS of ADs were not increased in NHL patients (nor vice versa). In the diseasome, NHLs shared more genetic etiology with ADs than solid cancers (p = .0041). A meta-analysis (combing AD with NHL) implicated genes of apoptosis and telomere length. This GWAS-based analysis four NHL subtypes and three ADs revealed few weakly-associated shared loci, explaining little total risk. This suggests common genetic variation, as assessed by GWAS in these sample sizes, may not be the primary explanation for the link between these ADs and NHLs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/gepi.22242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6763347PMC
October 2019

A multivariable approach for risk markers from pooled molecular data with only partial overlap.

BMC Med Genet 2019 07 19;20(1):128. Epub 2019 Jul 19.

Institute for Medical Biometry and Statistics, Faculty of Medicine and Medical Center - University of Freiburg, Stefan-Meier-Straße 26, Freiburg, 79104, Germany.

Background: Increasingly, molecular measurements from multiple studies are pooled to identify risk scores, with only partial overlap of measurements available from different studies. Univariate analyses of such markers have routinely been performed in such settings using meta-analysis techniques in genome-wide association studies for identifying genetic risk scores. In contrast, multivariable techniques such as regularized regression, which might potentially be more powerful, are hampered by only partial overlap of available markers even when the pooling of individual level data is feasible for analysis. This cannot easily be addressed at a preprocessing level, as quality criteria in the different studies may result in differential availability of markers - even after imputation.

Methods: Motivated by data from the InterLymph Consortium on risk factors for non-Hodgkin lymphoma, which exhibits these challenges, we adapted a regularized regression approach, componentwise boosting, for dealing with partial overlap in SNPs. This synthesis regression approach is combined with resampling to determine stable sets of single nucleotide polymorphisms, which could feed into a genetic risk score. The proposed approach is contrasted with univariate analyses, an application of the lasso, and with an analysis that discards studies causing the partial overlap. The question of statistical significance is faced with an approach called stability selection.

Results: Using an excerpt of the data from the InterLymph Consortium on two specific subtypes of non-Hodgkin lymphoma, it is shown that componentwise boosting can take into account all applicable information from different SNPs, irrespective of whether they are covered by all investigated studies and for all individuals in the single studies. The results indicate increased power, even when studies that would be discarded in a complete case analysis only comprise a small proportion of individuals.

Conclusions: Given the observed gains in power, the proposed approach can be recommended more generally whenever there is only partial overlap of molecular measurements obtained from pooled studies and/or missing data in single studies. A corresponding software implementation is available upon request.

Trial Registration: All involved studies have provided signed GWAS data submission certifications to the U.S. National Institute of Health and have been retrospectively registered.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12881-019-0849-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6642584PMC
July 2019

Psychophysiological insomnia and respiratory tract infections: results of an infection-diary-based cohort study.

Sleep 2019 08;42(8)

Institute for Immunodeficiency and Center for Chronic Immunodeficiency (CCI), Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Study Objectives: The immune theory of sleep suggests an important role of sleep for a functioning immune system. Insomnia has been associated with heightened risk for infections. The aim of the study was to test whether psychophysiological insomnia (PI) is associated with subsequent respiratory tract infections (RTIs) in the context of an infection-diary-based cohort study.

Methods: We recruited 674 adults from a cross-sectional survey on airway infections into the airway infection susceptibility (AWIS) cohort and invited them to self-report in diaries incident RTIs experienced during 7097 months (mean of 11.9 months of completed infection diaries per individual). The Regensburg Insomnia Scale (RIS) was assessed at baseline to measure PI. As outcome, we considered an infection diary score summing up prospectively reported RTIs.

Results: The RIS score correlated significantly with the infection diary score summarizing reported RTIs (correlation coefficient = 0.265, p < 0.001). Adjustments by putative confounders did only marginally affect this relationship. No significant differences in the relationship between RIS score and diary score were found for subgroups including those by gender, body mass index, perceived stress, and comorbidity. People affected by a combination of high PI and obesity were eight times more likely to belong to the group reporting the highest 10% of RTIs compared to the nonobese group with low RIS score (p < 0.001). A high RIS score in men was associated with a higher neutrophil-to-lymphocyte ratio, an indicator of inflammation.

Conclusions: Our data support the relevance of adequate sleep for an immune system ready to fight pathogens and prevent airway infections.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/sleep/zsz098DOI Listing
August 2019

Inflammatory potential of diet and risk of lymphoma in the European Prospective Investigation into Cancer and Nutrition.

Eur J Nutr 2020 Mar 22;59(2):813-823. Epub 2019 Mar 22.

Cancer Registry and Histopathology Department, "Civic-M. P. Arezzo" Hospital, ASP, Ragusa, Ragusa, Italy.

Introduction: Chronic inflammation plays a critical role in lymphomagenesis and several dietary factors seem to be involved its regulation. The aim of the current study was to assess the association between the inflammatory potential of the diet and the risk of lymphoma and its subtypes in the European Investigation into Cancer and Nutrition (EPIC) study.

Methods: The analysis included 476,160 subjects with an average follow-up of 13.9 years, during which 3,136 lymphomas (135 Hodgkin lymphoma (HL), 2606 non-Hodgkin lymphoma (NHL) and 395 NOS) were identified. The dietary inflammatory potential was assessed by means of an inflammatory score of the diet (ISD), calculated using 28 dietary components and their corresponding inflammatory weights. The association between the ISD and lymphoma risk was estimated by hazard ratios (HR) and 95% confidence intervals (CI) calculated by multivariable Cox regression models adjusted for potential confounders.

Results: The ISD was not associated with overall lymphoma risk. Among lymphoma subtypes, a positive association between the ISD and mature B-cell NHL (HR for a 1-SD increase: 1.07 (95% CI 1.01; 1.14), p trend = 0.03) was observed. No statistically significant association was found among other subtypes. However, albeit with smaller number of cases, a suggestive association was observed for HL (HR for a 1-SD increase = 1.22 (95% CI 0.94; 1.57), p trend 0.13).

Conclusions: Our findings suggested that a high ISD score, reflecting a pro-inflammatory diet, was modestly positively associated with the risk of B-cell lymphoma subtypes. Further large prospective studies on low-grade inflammation induced by diet are warranted to confirm these findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00394-019-01947-0DOI Listing
March 2020

Vitamin D status and its determinants in healthy pregnant women living in Switzerland in the first trimester of pregnancy.

BMC Pregnancy Childbirth 2019 Jan 8;19(1):10. Epub 2019 Jan 8.

Clinic of Obstetrics, University Hospital Zurich, Frauenklinikstrasse 10, CH-8091, Zurich, Switzerland.

Objectives: Our study aimed at assessing the prevalence and determinants of vitamin D deficiency (25-hydroxy-vitamin D [25(OH)D] < 20 ng/mL) in pregnant women in the first trimester living in Switzerland.

Methods: From September 2014 through December 2015, 204 pregnant women were conveniently recruited during their first clinical appointment at the Clinic of Obstetrics of the University Hospital Zurich (between week 6 and 12 of pregnancy). Blood samples were collected and a questionnaire focusing on lifestyle and skin colour was completed face-to-face with the responsible physician. Logistic regression analyses were performed with vitamin D status as dependent variable.

Results: 63.2% of the participating women were vitamin D deficient, and the median vitamin D concentration in the overall sample was 17.1 ng/mL [Q1, Q3: 9.78, 22.3]. The highest proportions of vitamin D deficiency were detected in women originating from Africa and Middle East (91.4% deficient, median vitamin D concentration of 10.7 ng/mL [Q1, Q3: 6.55, 14.45]) and from South-East Asia/Pacific (88.5% deficient, median vitamin D concentration of 8.4 ng/mL [Q1, Q3: 6.10, 14.88]). Multivariable logistic regression showed that significant risk factors of vitamin D deficiency were country of origin (women born in Switzerland and Germany had a lower risk than women born in other countries), smoking status (lower risk for former smokers) and intake of vitamin D supplements.

Conclusions: Our results confirm a high prevalence of vitamin D deficiency in this Swiss cohort, in particular in women coming from Asian and African countries, and underline the importance of appropriate counseling and vitamin D supplementation in early pregnancy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12884-018-2150-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6323787PMC
January 2019

Adherence to the mediterranean diet and lymphoma risk in the european prospective investigation into cancer and nutrition.

Int J Cancer 2019 07 5;145(1):122-131. Epub 2019 Feb 5.

Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), Turin, Italy.

There is a growing evidence of the protective role of the Mediterranean diet (MD) on cancer. However, no prospective study has yet investigated its influence on lymphoma. We evaluated the association between adherence to the MD and risk of lymphoma and its subtypes in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The analysis included 476,160 participants, recruited from 10 European countries between 1991 and 2001. Adherence to the MD was estimated through the adapted relative MD (arMED) score excluding alcohol. Cox proportional hazards regression models were used while adjusting for potential confounders. During an average follow-up of 13.9 years, 3,136 lymphomas (135 Hodgkin lymphoma [HL], 2,606 non-HL and 395 lymphoma not otherwise specified) were identified. Overall, a 1-unit increase in the arMED score was associated with a 2% lower risk of lymphoma (95% CI: 0.97; 1.00, p-trend = 0.03) while a statistically nonsignificant inverse association between a high versus low arMED score and risk of lymphoma was observed (hazard ratio [HR]: 0.91 [95% CI 0.80; 1.03], p-trend = 0.12). Analyses by lymphoma subtype did not reveal any statistically significant associations. Albeit with small numbers of cases (N = 135), a suggestive inverse association was found for HL (HR 1-unit increase = 0.93 [95% CI: 0.86; 1.01], p-trend = 0.07). However, the study may have lacked statistical power to detect small effect sizes for lymphoma subtype. Our findings suggest that an increasing arMED score was inversely related to the risk of overall lymphoma in EPIC but not by subtypes. Further large prospective studies are warranted to confirm these findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.32091DOI Listing
July 2019

Methodological issues in a prospective study on plasma concentrations of persistent organic pollutants and pancreatic cancer risk within the EPIC cohort.

Environ Res 2019 02 23;169:417-433. Epub 2018 Nov 23.

Department of Community Medicine, UiT-The Arctic University of Norway, Tromsø, Norway.

Background: The use of biomarkers of environmental exposure to explore new risk factors for pancreatic cancer presents clinical, logistic, and methodological challenges that are also relevant in research on other complex diseases.

Objectives: First, to summarize the main design features of a prospective case-control study -nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort- on plasma concentrations of persistent organic pollutants (POPs) and pancreatic cancer risk. And second, to assess the main methodological challenges posed by associations among characteristics and habits of study participants, fasting status, time from blood draw to cancer diagnosis, disease progression bias, basis of cancer diagnosis, and plasma concentrations of lipids and POPs. Results from etiologic analyses on POPs and pancreatic cancer risk, and other analyses, will be reported in future articles.

Methods: Study subjects were 1533 participants (513 cases and 1020 controls matched by study centre, sex, age at blood collection, date and time of blood collection, and fasting status) enrolled between 1992 and 2000. Plasma concentrations of 22 POPs were measured by gas chromatography - triple quadrupole mass spectrometry (GC-MS/MS). To estimate the magnitude of the associations we calculated multivariate-adjusted odds ratios by unconditional logistic regression, and adjusted geometric means by General Linear Regression Models.

Results: There were differences among countries in subjects' characteristics (as age, gender, smoking, lipid and POP concentrations), and in study characteristics (as time from blood collection to index date, year of last follow-up, length of follow-up, basis of cancer diagnosis, and fasting status). Adjusting for centre and time of blood collection, no factors were significantly associated with fasting status. Plasma concentrations of lipids were related to age, body mass index, fasting, country, and smoking. We detected and quantified 16 of the 22 POPs in more than 90% of individuals. All 22 POPs were detected in some participants, and the smallest number of POPs detected in one person was 15 (median, 19) with few differences by country. The highest concentrations were found for p,p'-DDE, PCBs 153 and 180 (median concentration: 3371, 1023, and 810 pg/mL, respectively). We assessed the possible occurrence of disease progression bias (DPB) in eight situations defined by lipid and POP measurements, on one hand, and by four factors: interval from blood draw to index date, tumour subsite, tumour stage, and grade of differentiation, on the other. In seven of the eight situations results supported the absence of DPB.

Conclusions: The coexistence of differences across study centres in some design features and participant characteristics is of relevance to other multicentre studies. Relationships among subjects' characteristics and among such characteristics and design features may play important roles in the forthcoming analyses on the association between plasma concentrations of POPs and pancreatic cancer risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envres.2018.11.027DOI Listing
February 2019
-->