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- Hess, Timo, et al.
(author)
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Dissecting the genetic heterogeneity of gastric cancer
- 2023
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In: EBioMedicine. - : Elsevier. - 2352-3964. ; 92
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Journal article (peer-reviewed)abstract
- Background: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett's oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture.Methods: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO.Findings: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level.Interpretation: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO.
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| 2. |
- Reissner, Volker, et al.
(author)
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Burnout, Coping and Job Satisfaction in Service Staff Treating Opioid Addicts-from Athens to Zurich
- 2010
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In: Stress and Health. - : Wiley. - 1532-3005 .- 1532-2998. ; 26:2, s. 149-159
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Journal article (peer-reviewed)abstract
- The Treatment-systems Research on European Addiction Treatment study (TREAT-project) is a longitudinal multicenter study on predominantly opioid-dependent patients and their health-care system in six European cities. As part of the examination of the drug services, this study evaluates level of burnout, coping strategies, perceived self-efficacy and job satisfaction among health-care workers treating opioid addicts. Employees were recruited from organizations in Athens, London, Padua, Stockholm, Zurich and Essen. The Maslach burnout inventory, Brief COPE, general self-efficacy questionnaire and a job satisfaction scale were filled in by about 383 drug service workers. One-third of the staff suffer from severe burnout. London and Stockholm colleagues are significantly more burdened than Zurich personnel where job satisfaction is highest. No cross-national differences could be detected concerning coping styles or level of perceived self-efficacy. Burnout is positively correlated to passive coping strategies and negatively linked to self-efficacy and job satisfaction. Males experience more depersonalization. Organizational features such as the entry-threshold level of the institution or out- vs. inpatient setting are relevant for coping strategies and job satisfaction. These and other findings are discussed in relation to preliminary data from the TREAT-project on characteristics of opioid addicted patients and other specific features of the drug treatment system.
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