Cytokine gene polymorphisms and atopic disease in two European cohorts. (ECRHS-Basel and SAPALDIA)

BACKGROUND: Atopy and allergic phenotypes are biologically characterized by an imbalanced T helper cell response skewed towards a type 2 (TH2) immune response associated with elevated serum immunoglobulin E (IgE) levels. Polymorphisms in cytokine genes might modulate regulation of the TH1/TH2 balance. We thus aimed at reproducing our previous findings from a European study population on the association of various cytokine polymorphisms with self-reported hay fever as well as increased total and specific IgE levels in two comparable study populations. METHODS: Two prospective Caucasian cohorts were used. In the Basel center of the European Community Respiratory Health Survey (ECRHS, n = 418) ten distinct cytokine polymorphisms of putative functional relevance were genotyped. In the Swiss cohort Study on Air Pollution And Lung Disease In Adults (SAPALDIA, n = 6003) two cytokine polymorphisms were genotyped. The associations of these polymorphisms with atopy were estimated by covariance and logistic regression analysis. RESULTS: We confirmed IL4, IL10, IL6 and IL18 as candidate genes for atopic health outcomes. In the large, well-characterized SAPALDIA cohort the IL6(-174G>C) and IL18(-137G>C) polymorphisms were associated with circulating total IgE concentrations in subjects with hay fever. The IL18(-137G>C) polymorphism was also associated with the prevalence of hay fever. CONCLUSION: Comprehensive characterization of genetic variation in extended cytokine candidate gene regions is now needed. Large study networks must follow to investigate the association of risk patterns defined by genetic predisposing and environmental risk factors with specific atopic phenotypes

Single nucleotide polymorphisms of matrix metalloproteinase 9 (MMP9) and tumor protein 73 (TP73) interact with Epstein-Barr virus in chronic lymphocytic leukemia: results from the European case-control study EpiLymph

Using EpiLymph case-control data, we found that chronic lymphocytic leukemia patients were more likely to have abnormal reactive serological patterns to Epstein Barr virus than controls. Here, we aimed to assess whether this association is modified by genetic variants. We examined 1,305 Single Nucleotide Polymorphisms from 300 selected genes related to various pathways in 240 cases and 513 controls from five European centers. In a recessive model, patients positive to aberrant antibody pattern and homozygous for rare genotypes in rs8113877T>G or rs17576A>G of the MMP9 gene were at highest risk of chronic lymphocytic leukemia. In a dominant model, TP73 showed the highest risk in patients positive to aberrant antibody pattern and homozygous for the wild-type genotype in rs1885859G>C or rs3765701A>T. All interactions were additive and no main effect was observed. The strong interactions observed may be indicative of a specific pathway in cancer genesis. Confirmation of these results is warranted

Tobacco smoking, alcohol drinking and Hodgkin's lymphoma: a European multi-centre case–control study (EPILYMPH)

We analysed the effects of tobacco and alcohol in the aetiology of Hodgkin's lymphoma (HL), based on 340 cases and 2465 controls enrolled in Spain, France, Italy, Germany, Ireland and Czech Republic, between 1998 and 2004. Current smokers showed a significantly increased odds ratio (OR) of HL of 1.39 (95% confidence interval (CI)=1.04–1.87). Analyses were also conducted separately for subjects younger than 35 years (179 cases) and for older subjects (161 cases). For subjects below age 35, no association was observed between tobacco and HL, whereas for older subjects, ever-smokers experienced a doubled risk of HL as compared to never smokers and the OR of HL for current smoking was 2.35 (95% CI=1.52–3.61), with suggestion of a dose–response relationship. A protective effect of alcohol was observed in both age groups. The OR for ever-regular drinking was 0.58 (95% CI=0.38–0.89) for younger subjects and 0.50 (95% CI=0.34–0.74) for older subjects. There was no evidence of interaction between tobacco and alcohol. Our results are consistent with previous studies, suggesting a protective effect of alcohol on HL. An effect of tobacco was suggested for HL occurring in middle and late age, although this finding might have occurred by chance

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

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. Whilst increased infection susceptibility is a well-known initial IEI manifestation, less is known about the frequency of other presenting manifestations. / Objective: 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 (ESID) registry. Patients with autoinflammatory diseases were excluded due to 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 due to family history only and 0.8% presented with malignancy. Two thirds of IEI patients presented before the age of 6 years, but a quarter of patients only developed initial symptoms as adults. Immune dysregulation was most frequently recognized as an initial IEI manifestation between 6 and 25 years of age with male predominance until age 10, shifting to female predominance after age 40. Infections were most prevalent as a first manifestation in patients presenting after age 30. / Conclusion: An exclusive focus on infection-centered warning signs would have missed around 25% of IEI patients that initially present with other manifestations. / Clinical implications: We provide a data-based rationale to add immune dysregulation and syndromic features to the IEI warning signs, which may significantly improve early IEI diagnosis

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

Визначення понять «резидент» і «нерезидент»: проблеми теорії і практики

Досліджено практику застосування понять «резидент» та «нерезидент» у як в Україні так і окремих зарубіжних країнах, а також надано авторське бачення щодо визначення даних термінів. Автори статті визначають умови оподаткування операцій з нерезидентами з огляду на існуючі особливості правозастосовної діяльності і вно­сять окремі пропозиції щодо удосконалення процедури адміністрування податків, що стягуються з нерезидентів.Исследована практика применения понятий «резидент» и «нерезидент» как в Украине, так и отдельных зарубежных странах, а также предоставлено авторское виденье относительно определения данных терминов. Авторы статьи определяют условия налогообложения операций с нерезидентами, учитывая существующие особен­ности правоприменительной деятельности, вносят отдельные предложения относи­тельно усовершенствования процедуры администрирования налогов, которые удержи­ваются из нерезидентов.Іn this article practice of application of concepts «resident» and «non­resident» are explored both in Ukraine and some foreign countries, and granted the author’s view on the definition of these terms. The authors of the article determine the term of taxation of operations with non­residents, taking into account the existing features of legal activity and make some suggestions in relation to the improvement of procedure of administration of taxes which are tightened from non­residents

Методологія вітчизняної кримінально-правової науки: становлення історичного методу та проблеми наступності

Аналізуються методологічні проблеми кримінально-правової науки, зокрема процес становлення історичного методу та його ролі у вивченні питань наступності в кримінальному праві.Анализируются методологические проблемы уголовно-правовой науки, в частности процесс становления исторического метода и его роли в изучении вопросов преемственности в уголовном праве.The paper is devoted to an analysis of methodological problems of a criminal legal sci­ence, namely, an establishing process of historical method and its role in studying succession issues in a criminal law

Hepatitis C and Non-Hodgkin Lymphoma Among 4784 Cases and 6269 Controls From the International Lymphoma Epidemiology Consortium

Background & Aims: increasing evidence points towards a role of hepatitis C virus (HCV) infection in causing malignant lymphomas. We pooled case-control study data to provide robust estimates of the risk of non-Hodgkin's lymphoma (NHL) subtypes after HCV infection. Methods: The analysis included 7 member studies from the International Lymphoma Epidemiology Consortium (InterLymph) based in Europe, North America, and Australia. Adult cases of NHL (n = 4784) were diagnosed between 1988 and 2004 and controls (n = 6269) were matched by age, sex, and study center. All studies used third-generation enzyme-linked immunosorbent assays to test for antibodies against HCV in serum samples. Participants who were human immunodeficiency virus positive or were organ-transplant recipients were excluded. Results: HCV infection was detected in 172 NHL cases (3.60%) and in 169 (2.70%) controls (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.40 -2.25). In subtype-specific analyses, HCV prevalence was associated with marginal zone lymphoma (OR, 2.47; 95% CI, 1.44-4.23), diffuse large B-cell lymphoma (OR, 2.24; 95% CI, 1.682.99), and lymphoplasmacytic lymphoma (OR, 2.57; 95% CI, 1.14-5.79). Notably, risk estimates were not increased for follicular lymphoma (OR, 1.02; 95% CI, 0.65-1.60). Conclusions: These results confirm the association between HCV infection and NHL and specific B-NHL subtypes (diffuse large B-cell lymphoma, marginal zone lymphoma, and lymphoplasmacytic lymphoma)