Genetic variation associated with chromosomal aberration frequency: A genome-wide association study

Chromosomal aberrations (CAs) in human peripheral blood lymphocytes (PBL) measured with the conventional cytogenetic assay have been used for human biomonitoring of genotoxic exposure for decades. CA frequency in peripheral blood is a marker of cancer susceptibility. Previous studies have shown associations between genetic variants in metabolic pathway, DNA repair and major mitotic checkpoint genes and CAs. We conducted a genome-wide association study on 576 individuals from the Czech Republic and Slovakia followed by a replication in two different sample sets of 482 (replication 1) and 1288 (replication 2) samples. To have a broad look at the genetic susceptibility associated with CA frequency, the sample sets composed of individuals either differentially exposed to smoking, occupational/environmental hazards, or they were untreated cancer patients. Phenotypes were divided into chromosome- and chromatid-type aberrations (CSAs and CTAs, respectively) and total chromosomal aberrations (CAtot). The arbitrary cutoff point between individuals with high and low CA frequency was 2% for CAtot and 1% for CSA and CTA. The data were analyzed using age, sex, occupation/cancer and smoking history as covariates. Altogether 11 loci reached the P-value of 10⁻⁵ in the GWAS. Replication 1 supported the association of rs1383997 (8q13.3) and rs2824215 (21q21.1) in CAtot and rs983889 (5p15.1) in CTA analysis. These loci were found to be associated with genes involved in mitosis, response to environmental and chemical factors and genes involved in syndromes linked to chromosomal abnormalities. Identification of new genetic variants for the frequency of CAs offers prediction tools for cancer risk in future. Environ. Mol. Mutagen. 60:17–28, 2019. © 2018 Wiley Periodicals, Inc.     

A historical job-exposure matrix for occupational exposure to diesel exhaust using elemental carbon as an indicator of exposure

Abstract

Any study of the long-term health effects of diesel exhaust exposure requires past exposure to be assessed. Few historical measurements of occupational exposure to elemental carbon (EC) are available, so past exposure must be assessed using models and judgments based on indirect data. A job-exposure matrix (JEM) for historical occupational exposure to diesel exhaust based on EC is presented. Past exposure to EC in occupations with a high exposure to diesel exhaust was assessed using an eight-step process. The assessments were based on technical specific data and NO₂-exposure data, and a current EC-exposure measurement program. Finally, group assessment was carried out by consensus. Temporal variations in exposure were assessed for different groups. The matrix was constructed to assess annual average EC exposure for 72 occupations between 1950 and 2004. EC exposure between 1950 and 2004 varied between 1 and 247?µg/m³, for farmers in 2000 and miners in 1975 respectively, and was generally highest in the 1970s. The JEM allows lifetime diesel exhaust exposure intensity in 72 occupations to be assessed and used in epidemiological studies.     

A Swedish Mutual Support Society of Problem Gamblers

Mutual support societies for problem gamblers have existed in Sweden for 20?years. They have helped more people with gambling problems than any other institution inside or outside the Swedish health care system. This paper outlines the background of these societies and describes the meetings of one of them. Data come from interviews with members of a local society and participation in mutual support meetings. It is argued that these mutual support societies provide help in a variety of ways and in all phases of recovery from gambling problems. In particular, they help people form personal narratives about the origin, progression, and resolution of their problems, narratives that give insight and guide recovery. These mutual support societies are valuable complements and alternatives to professional treatment.     

Silica nanoparticles induce cytokine responses in lung epithelial cells through activation of a p38/TACE/TGF-α/EGFR-pathway and NF-κΒ signalling

Amorphous silica nanoparticles (SiNPs) have previously been shown to induce marked cytokine (interleukin-6; IL-6 and interleukin-8; CXCL8/IL-8) responses independently of particle uptake in human bronchial epithelial BEAS-2B cells. In this study the involvement of the mitogen-activated protein kinases (MAP-kinases), nuclear factor-kappa Β (NF-κΒ) and in particular tumour necrosis factor-α converting enzyme (TACE) and—epidermal growth factor receptor (EGFR) signalling pathways were examined in triggering of IL-6 and CXCL8 release after exposure to a 50 nm silica nanoparticle (Si50). Exposure to Si50 increased phosphorylation of NF-κΒ p65 and MAP-kinases p38 and JUN-N-terminal protein kinase pathways (JNK), but not extracellular signal regulated kinases (ERK). Inhibition of NF-κΒ and p38 reduced the cytokine responses to Si50, whereas neither JNK- nor ERK-inhibition exerted any significant effect on the responses to Si50. Increases in membrane-bound transforming growth factor-α (TGF-α) release and EGFR phosphorylation were also observed after Si50 exposure, and pre-treatment with inhibitors of these pathways reduced the release of IL-6 and CXCL8, but did not affect the Si50-induced phosphorylation of p38 and p65. In contrast, p38-inhibition partially reduced Si50-induced TGF-α release, while the p65-inhibition was without effect. Overall, our results indicate that Si50-induced IL-6 and CXCL8 responses in BEAS-2B cells were regulated through combined activation of several pathways, including NF-κΒ and p38/TACE/TGF-α/EGFR signalling. The study identifies critical, initial events in the triggering of pro-inflammatory responses by nanoparticles.     

Determinants for High Maternal Mortality in Multiethnic Populations in Western China

Our purpose of this study was to investigate determinants and patterns of associations with high maternal mortality in poor and multiethnic populations from the Xinjiang Uigur autonomous region of Western China. The researcher found that the maternal mortality ratio of Xinjiang was very high; almost half of the participants delivered at home without clean delivery, and nearly one-fifth of the participants had not received any medical treatment. Eighty-seven percent of maternal deaths were among ethnic minority groups. In multiethnic areas in Xinjiang, social–culture factors, lack of health resources, and low health services utilization were related to high maternal mortality.