Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes

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

Families Navigating the Landscape of Consumption in the Swedish Welfare Society

Swedish welfare policy has in several ways promoted the individual rather than the family as a unit. This is not a phenomenon happening only in Sweden, but one occurring in many other Western countries where individualization is strongly emphasized. Sweden is, however, interesting as an example of a country with deep collective roots regarding issues of welfare. The welfare state has been, and to a major part still is, the main provider of social services, a fact that has affected the Swedish family in certain ways. During the last decades, the Swedish welfare society has changed toward marketization implying that individuals and families have to take on more responsibility regarding their welfare. The aim of this article is to discuss the transformation of Swedish families as consumers reflecting upon the effects of the Swedish welfare society

Apgar score and perinatal death after one previous caesarean delivery

Objective To assess the impact of the indication for a previous caesarean section on the outcome of a subsequent delivery. Design Population-based cohort study. Setting Sweden. Population Women with two deliveries between 1987 and 2007 identified using the Swedish Medical Birth Registry. Methods The outcome of 69 133 pregnancies after one caesarean section was compared with the outcome of 487 610 pregnancies following one vaginal delivery. The indication for the first caesarean section was estimated using a new hierarcharchical system based on information from birth records. Main outcome measures Perinatal death, low Apgar score (less than seven at 5 minutes). Results Infants of women with one previous caesarean section were at increased risk of low Apgar score compared with infants of women with one previous vaginal delivery (OR, 2.0; 95% CI, 1.9-2.1). The risk estimate was reduced when adjustment for maternal and fetal/infant characteristics was made (OR, 1.6; 95% CI, 1.5-1.8). The corresponding crude and adjusted odds ratios for perinatal death were 1.6 (95% CI, 1.4-1.7) and 1.1 (95% CI, 1.0-1.2), respectively. The infant outcome of the delivery after one caesarean section was mainly dependent on the indication for the first-delivery caesarean section and, when no medical indication was present, no increase in risk was detected. Conclusions Infants of women with one previous caesarean section were at increased risk of low Apgar score and/or perinatal death compared with infants of women with one previous vaginal delivery. The results suggest that medical conditions, not the previous caesarean section per se, contributed to the increase in risk

Antimicrobial resistance in colonizing group B Streptococci before the implementation of a Swedish intrapartum antibiotic prophylaxis program

The prevalence of antibiotic resistance and their genetic determinants in colonizing group B streptococci (GBS) sampled in a Swedish nationwide survey was examined. In five GBS isolates (1.3%), kanamycin/amikacin resistance and the presence of the aphA-3 gene was identified. Three of these isolates carried the aad-6 gene and were streptomycin-resistant. Screening with kanamycin and streptomycin 1,000-mu g disks enabled a rapid and easy detection of these isolates. In all, 312/396 (79%) GBS were tetracycline-resistant and 95% of the examined isolates harbored the tetM gene. Among the 22 (5.5%) GBS resistant to erythromycin and/or clindamycin, the ermB gene was detected in nine isolates (41%) and erm(A/TR) in ten isolates (45%). A high level of erythromycin and clindamycin resistance with minimum inhibitory concentrations (MICs) > 256 mg/L was found in four serotype V isolates that harbored ermB. The erythromycin/clindamycin resistance was distributed among all of the common serotypes Ia, Ib, II, III, IV, and V, but was not present in any of the 44 serotype III isolates associated to clonal complex 17. Screening for penicillin resistance with 1-mu g oxacillin disks showed a homogenous population with a mean inhibition zone of 20 mm. A change in the present oxacillin breakpoints for GBS is suggested

Consumer Projects: Cultural Resources and the Pursuit of Consumer Agency

Consumer projects, such as Do-it-Yourself (DIY) projects are a pervasive yet highly involving form of consumption in the United States. Among other things, perhaps at their core, consumer projects have a cultural model of agentic experience and action. North American consumers use consumer projects to craft deeply meaningful, creative, and even transcendental experiences in which consumers see themselves as agentic actors. Our presentation examines how and under what conditions consumers generate a sense of consumer agency through their projects. We examine various consumer projects, such as home improvement, car tuning, bike fixing, and house painting and illuminate the relationships between cultural resources and agentic experiences

Non-Hodgkin Lymphoma, Body Mass Index, and Cytokine Polymorphisms: A Pooled Analysis from the InterLymph Consortium

BACKGROUND: Excess adiposity has been associated with lymphomagenesis, possibly mediated by increased cytokine production causing a chronic inflammatory state. The relationship between obesity, cytokine polymorphisms and selected mature B-cell neoplasms is reported. METHOD: Data on 4979 cases and 4752 controls from nine American/European studies from the InterLymph consortium (1988–2008) were pooled. For diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL), joint associations of body mass index (from self-reported height and weight) and 12 polymorphisms in cytokines IL1A (rs1800587), IL1B (rs16944, rs1143627), IL1RN (rs454078), IL2 (rs2069762), IL6 (rs1800795, rs1800797), IL10 (rs1800890, rs1800896), TNF (rs1800629), LTA (rs909253), and CARD15 (rs2066847) were investigated using unconditional logistic regression. BMI-polymorphism interaction effects were estimated using the relative excess risk due to interaction (RERI). RESULTS: Obesity (BMI≥30kg m(−2)) was associated with DLBCL risk (OR=1.33, 95%CI 1.02–1.73), as was TNF-308GA+AA (OR=1.24, 95%CI 1.07–1.44). Together, being obese and TNF-308GA+AA increased DLBCL risk almost two-fold relative to those of normal weight and TNF-308GG (OR=1.93 95%CI 1.27–2.94), with a RERI of 0.41 (95%CI −0.05,0.84, P(interaction)=0.13). For FL and CLL/SLL, no associations with obesity or TNF-308GA+AA, either singly or jointly, were observed. No evidence of interactions between obesity and the other polymorphisms were detected. CONCLUSIONS: Our results suggest that cytokine polymorphisms do not generally interact with BMI to increase lymphoma risk but obesity and TNF-308GA+AA may interact to increase DLBCL risk. IMPACT: Studies using better measures of adiposity are needed to further investigate the interactions between obesity and TNF-308G>A in the pathogenesis of lymphoma

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

Background: We explored the interaction between non-Hodgkin lymphoma (NHL), infectious mononucleosis (IM) history, and immune-related genotypes in a pooled case-control analysis. Methods: 7926 NHL patients and 10 018 controls from 12 studies were included. Self-reported IM history and genotypes were provided by the InterLymph Data Coordinating Center at Mayo Clinic. Odds ratios (OR) were estimated using multivariate logistic and linear regression, and interactions with the empirical Bayes method. Bonferroni corrections and pACT were 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 (pinteraction= 0.02, ORinteraction = 0.09, 95% confidence interval [CI] = 0.01, 0.87) and rs1800797 in interleukin-6 (pinteraction = 0.02, ORinteraction=0.08, 95% CI = 0.01, 0.80). Neither interaction effect withstood adjustment for multiple comparisons. Among controls, increasing socioeconomic status (OR = 1.69, 95% CI = 1.48, 1.93) and female sex (OR = 1.53, 95% CI = 1.26, 1.87) were positively associated with IM. Large sibship size (3+) was inversely associated with IM among controls born before 1960 (OR<1960 = 0.40, 95% CI = 0.24, 0.67), but not after. Conclusions: Genetic risk variants in IL1B and IL6 may affect the association between IM and TCL. Risk factors for IM are consistent with lower Epstein-Barr virus exposure in early life; the association with female sex is unexplained. Keywords: Infectious mononucleosis, non-Hodgkin lymphoma, T-cell lymphoma, genotype, interleukin 1B, interleukin 6, siblings, family size, socioeconomic status Key Messages • A suggestion that genetic variation in interleukin-1B (IL1B) and interleukin-6 (IL6) may attenuate the association between infectious mononucleosis and T-cell lymphoma requires confirmation with larger numbers. • Increasing socioeconomic status and female sex are independently associated with self-reported infectious mononucleosis. • The number of siblings is inversely associated with self-reported infectious mononucleosis among those born before 1960 but not those born after