Vitamin D and parathyroid hormone in the umbilical cord blood - Correlation with light and dark maternal skin color

During pregnancy, vitamin D deficiency is associated with negative health consequences for mother and child. Furthermore, dark skin color is associated with lower vitamin D levels. We investigated 25-hydroxy-vitamin D (25(OH)D) and parathyroid hormone (PTH) levels in mothers and in cord blood of their newborns depending on maternal skin color. We recruited 202 mother and child pairs at the University Hospital Zurich and measured 25(OH)D and PTH concentrations in maternal and postpartum umbilical cord blood. Skin type was self-reported based on the Fitzpatrick Scale (type I to V). Uni- and multivariate methods were used to compare the maternal and neonatal 25(OH)D and PTH levels by skin type (light: I-III vs. dark: IV-V). As many as 54.5% of all mothers and 41.1% of the neonates were 25(OH)D deficient. This was higher in the neonates of dark-skinned (55.9%) than in the neonates of light-skinned mothers (38.1%; p = .06). The correlation of 25(OH)D in the maternal with umbilical cord blood was high (light: r = 0.85, dark: r = 0.87), with higher concentrations of 25(OH) vitamin D in the umbilical cord than in maternal blood. Regression analysis revealed that country of origin and maternal 25(OH)D concentration were the only statistically significant determinants for umbilical cord blood 25(OH)D. We observed no correlation of maternal with umbilical cord PTH concentrations; median PTH concentrations in the umbilical cord (5.6 pg/ml) were significantly lower than in maternal blood (25.7 pg/ml). The recommendation of vitamin D supplementation in newborns in their first 3 years of life should be particularly emphasized to dark-skinned mothers

Genetic Polymorphisms in Genes Related to Oxidative Stress (GSTP1, GSTM1, GSTT1, CAT, MnSOD, MPO, eNOS) and Survival of Rectal Cancer Patients after Radiotherapy

Radiotherapy exerts part of its antineoplastic effect by generating oxidative stress, therefore genetic variation in oxidative stress-related enzymes may influence survival of rectal cancer patients. We hypothesized that genetic polymorphisms associated with higher amounts of reactive oxygen species (ROS) that exaggerate cytotoxic activity could improve survival after radiotherapy. We followed 114 rectal cancer patients who received radiotherapy for an average of 42.5 months. Associations between genotypes (GSTP1, GSTM1, GSTT1, CAT, MnSOD, MPO and eNOS) and overall survival were assessed using Kaplan-Meier curves and Cox proportional hazards regression. As hypothesized, patients carrying low ROS producing eNOS Glu298Asp asparagine allele showed an increased hazard of death compared to homozygous carriers of the glutamine allele (hazard ratio (HR): 2.10, 95% confidence interval (CI): 1.01–4.38). However, carriers of low ROS producing MPO G463A A allele had a decreased hazard of death compared to patients homozygous for the G allele (HR: 0.44, 95% CI: 0.21–0.93) although patients homozygous for the A allele had a slightly increased hazard (HR: 1.12, 95% CI: 0.25–5.08). This explorative study provides first results and highlights the need for further, larger studies to investigate association between genetic variation in oxidative stress genes and survival of rectal cancer patients who received radiotherapy

Research on Rare Diseases in Germany – The GAIN Registry: a registry for individuals with congenital multi-organ autoimmune diseases

Background: Patient registries are an important tool for networking medical caregivers and research, especially in the field of rare diseases. Individuals afflicted by multi-organ autoimmune diseases typically suffer from inflammation of multiple organs. Project: GAIN (German genetic multi-organ Auto-Immunity Network) is the German network for research and therapy optimisation for individuals with congenital multi-organ autoimmune diseases. As a sub-project of the network, the registry systematically collects data from this patient group and makes it available for research purposes. Results: A data set was developed and made available for the GAIN Registry that can map the complex clinical status of persons with multi-organ autoimmune diseases. Data from 486 individuals have been documented to date. Conclusions: The GAIN register allows for a very comprehensive documentation that clearly goes beyond previous approaches, e.g. by linking it to biosamples collected in the consortium. The planned inclusion of patients in the documentation, e.g. of data on quality of life, opens up a new field

Multiple Myeloma and lifetime occupation: results from the EPILYMPH study

Background: The EPILYMPH study applied a detailed occupational exposure assessment approach to a large multi-centre case-control study conducted in six European countries. This paper analysed multiple myeloma (MM) risk associated with level of education, and lifetime occupational history and occupational exposures, based on the EPILYMPH data set. Methods: 277 MM cases and four matched controls per each case were included. Controls were randomly selected, matching for age (+/- 5 years), centre and gender. Lifetime occupations and lifetime exposure to specific workplace agents was obtained through a detailed questionnaire. Local industrial hygienists assessed likelihood and intensity for specific exposures. The odds ratio and 95% confidence intervals (OR, 95% CI) were calculated for level of education, individual occupations and specific exposures. Unconditional logistic regression models were run for individual occupations and exposures. Results: A low level of education was associated with MM OR = 1.68 (95% CI 1.02-2.76). An increased risk was observed for general farmers (OR = 1.77; 95% CI 1.05-2.99) and cleaning workers (OR = 1.69; 95% CI 1.04-2.72) adjusting for level of education. Risk was also elevated, although not significant, for printers (OR = 2.06; 95% CI 0.97-4.34). Pesticide exposure over a period of ten years or more increased MM risk (OR = 1.62; 95% CI 1.01-2.58). Conclusion: These results confirm an association of MM with farm work, and indicate its association with printing and cleaning. While prolonged exposure to pesticides seems to be a risk factor for MM, an excess risk associated with exposure to organic solvents could not be confirmed

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

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

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

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

Evaluation of a questionnaire to assess selected infectious diseases and their risk factors: Findings of a multicenter study

Background/objectives The risk to die from an infectious disease in Germany has been continuously decreasing over the last century. Since infections are, however, not only causes of death but risk factors for diseases like cardiovascular diseases, it is essential to monitor and analyze their prevalence and frequency, especially in consideration of the increased life expectancy. To gain more knowledge about infectious diseases as risk factors and their implications on the condition and change of the immune status, the German National Cohort (GNC), a population-based prospective cohort study, will recruit 200,000 subjects between 2014 and 2017. In Pretest 1, a feasibility study for the GNC, we evaluated a self-administered and self-report questionnaire on infectious diseases and on the use of health care facilities (hereinafter called “ID Screen”) for feasibility and validity. Methods: From August–November 2011, 435 participants between the ages of 20–69 completed the ID Screen. All subjects had been recruited via a random sample from the local residents’ registration offices by 4 of the 18 participating study centers. The questionnaire encompasses 77 variables in six sections assessing items such as 12-month prevalence of infections, cumulative prevalence of infectious diseases, visit of health care facilities and vaccination. The feasibility was amongst others evaluated by assessing the completeness and comprehensiveness of the questionnaire. To assess the questionnaires ability to measure “immune status” and “susceptibility to infections”, multivariate analysis was used. Results: The overall practicability was good and most items were well understood, demonstrated by 5 % of missing values. However, direct comparison of the items 12-month prevalence and lifetime prevalence of nephritis/pyelitis showed poor agreement and thereby poor understanding by 80 % of the participants, illustrating the necessity for a clear, lay person appropriate description of rare diseases to increase comprehensibility. The questionnaire will be used to support the assessment of immune dysfunction and frequency of infection. An analysis of these constructs in an exploratory factor analysis revealed limited applicability due to low interitem correlation (Cronbach’s α < 0.5). This is corroborated by the extraction of more than one factor with a Kaiser–Meyer–Olkin measure of 0.6 instead of a unidimensional latent construct for “immune status”. Conclusion: All in all, the ID Screen is a good and reliable tool to measure infectious diseases as risk factors and outcome in general, but requires a better translation of infection specific terms into lay person terms. For the assessment of the overall immune status, the tool has strong limitations. Vaccinations status should also rather be assessed based on vaccination certificates than on participants’ recall. Electronic supplementary material The online version of this article (doi: 10.1007/s00103-014-2052-y) contains supplementary material, which is available to authorized users

Forschung zu Seltenen Erkrankungen in Deutschland - Das GAIN-Register: Ein Register für Personen mit angeborenen Multi-Organ-Autoimmunerkrankungen

Hintergrund: Patientenregister sind insbesondere im Bereich der seltenen Erkrankungen ein wichtiges Instrument für die Vernetzung der medizinischen Betreuenden und die Forschung. Bei Multi-Organ-Autoimmunerkrankungen leiden Betroffene typischerweise an Entzündungen mehrerer Organe. Projekt: GAIN (German genetic multi-organ Auto-Immunity Network) ist das deutsche Netzwerk für die Erforschung und Therapieoptimierung von Personen mit angeborenen Multi-Organ-Autoimmunerkrankungen. Als ein Teilprojekt des Netzwerks erfasst das Register Daten dieser Patientengruppe systematisch und stellt sie für die Forschung zur Verfügung. Ergebnisse: Für das GAIN-Register wurde ein Datensatz entwickelt und bereitgestellt, der die komplexen Krankheitsbilder von Personen mit Multi-Organ-Autoimmunerkrankungen abbilden kann. Bisher wurden die Daten von 486 Personen dokumentiert. Schlussfolgerungen: Das GAIN-Register erlaubt eine sehr umfassende Dokumentation, die deutlich über bisherige Ansätze hinausgeht, bspw. durch die Verknüpfung mit im Konsortium gesammelten Bioproben. Durch das geplante Einbeziehen der Patientinnen und Patienten in die Dokumentation, z. B. von Daten zur Lebensqualität, wird ein neuer Bereich erschlossen

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

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