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- Kaerlev, L, et al.
(författare)
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Occupational risk factors for small bowel carcinoid tumor: A European population-based case-control study
- 2002
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Ingår i: Journal of Occupational and Environmental Medicine. - 1536-5948. ; 44:6, s. 516-522
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Tidskriftsartikel (refereegranskat)abstract
- Small bowel carcinoid tumor (SBC) is a rare disease of unknown etiology bill with all age-, sex-, and place-specific occurrence that may indicate an occupational origin. A European multicenter population-based case-control study was conducted from 1995 through 1997. Incident SBC cases between 35 and 69 years of age (n = 101) were identified, together with 3335 controls sampled from the catchment area of the cases. Histological review performed by a reference pathologist left 99 cases for study; 84 cases and 2070 population controls were interviewed. The industries most closely associated (a twofold or more odds ratio [OR]) with SBC taking into account a 10-year time lag after exposure were, among women, employment in wholesale industry of food and beverages (OR, 8.2; 95% confidence interval [CI], [1.9 to 34.9]) and among men, manufacture of motor vehicle bodies (OR, 5.2; 95% CI, 1.2 to 22.4), footwear (OR, 3.9: 95% CI, 0.9 to 16.1), and metal structures (OR, 3.3; 95% CI, 1.0 to 10.4). The identified high-risk occupations with all OR above 2 were shoemakers, structural metal preparers, construction painters and other construction workers. bookkeepers, machine fitters, and welders (men). The OR for regular occupational use of organic. solvents for at least half a year was 2.0 (95% CI, 1.0 to 4.2). Exposure to rust-preventive paint containing lead was suggested as another potential occupational exposure (OR, 9.1; 95% CI, 0.8 to 107). This explorative study suggests an association between certain occupational exposures and SBC, bill some of these associations could be attributable to chance. All findings should be regarded as tentative.
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- Kaerlev, L, et al.
(författare)
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The importance of smoking and medical history for development of small bowel carcinoid tumor: a European population-based case-control study
- 2002
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Ingår i: Cancer Causes and Control. - 1573-7225. ; 13:1, s. 27-34
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Little is known about the etiology of small bowel carcinoid tumor (SBC), but a few studies have pointed to certain medical and lifestyle factors as potential risk factors. This study aims to evaluate these findings and to identify new associations. Methods: A population-based European multicenter case-control study was conducted from 1995 through 1997. Incident histologically verified 35-69 year-old SBC cases (n = 99) and 3335 controls were recruited; 84 cases and 2070 controls were interviewed. Results: Ever being a smoker was associated with SBC (odds ratio = 1.9; 95% confidence interval 1.1-3.2) and increased risk estimates were seen for all smoking categories. SBC was associated with previous gallstone disease and ovariectomy, but only when these conditions occurred within two years prior to the SBC diagnosis. No association was seen for a history of cholecystitis, liver cirrhosis, ulcerative disease, or Crohn's disease. Intake of alcoholic beverages - as well as medical treatments with radioactive substances, hormones, or corticosteroid tablets - were not associated with SBC. Conclusions: This study indicates that tobacco smoking is a risk factor for SBC. The associations with gallstone and ovarian diseases may be due to enhanced medical surveillance during the early phase of the cancer disease.
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- Pedersen, LN, et al.
(författare)
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Glutathione S-transferase genotype and p53 mutations in adenocarcinoma of the small intestine
- 2003
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 38:8, s. 845-849
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Tidskriftsartikel (refereegranskat)abstract
- Adenocarcinoma of the small intestine (ASI) is a rare disease of unknown aetiology. The glutathione S-transferase M1 (GSTM1) enzyme catalyses the detoxification of compounds involved in carcinogenesis of adenocarcinoma of the stomach, colon and lung, including constituents of tobacco smoke. We investigated a possible interaction between the lack of GSTM1 enzyme activity and the carcinogenic compounds of tobacco smoke. Based on the theory that certain carcinogens cause specific point mutations in the p53 gene we analysed by single strand conformation polymorphism (SSCP) and sequencing, p53 exon 5-8 of 52 samples of ASI collected in Sweden, Germany, France, Italy and Denmark between 1995 and 1997. The GSTM1 gene status was investigated by multiplex PCR. The prevalence of GSTM1 negative genotype among cases with ASI was 69% and higher than previous reports of 50% suggesting a higher risk of ASI among GSTM1 negative compared with GSTM1 positive subjects. A 'case-only' approach was used to address the combined association between the GSTM1 negative genotype and lifestyle exposures in patients with ASI. Using this method, heavy smokers (>20 pack-years) with the GSTM1 negative genotype had an odds ratio of 4.8; 95% confidence interval (CI) (0.6-38.7) for ASI as compared to smokers who expressed GSTM1. No similar association between alcohol consumption and ASI was found. No p53 mutations in exon 5-8 were found in these samples, but the method may not be sensitive enough to identify smaller differences. Thus p53 does not seem to be the target of carcinogens acting in the small intestine.
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- Van Mieghem, NM, et al.
(författare)
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Self-expanding Transcatheter vs Surgical Aortic Valve Replacement in Intermediate-Risk Patients: 5-Year Outcomes of the SURTAVI Randomized Clinical Trial
- 2022
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Ingår i: JAMA cardiology. - : American Medical Association (AMA). - 2380-6591 .- 2380-6583. ; 7:10, s. 1000-1008
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Tidskriftsartikel (refereegranskat)abstract
- In patients with severe aortic valve stenosis at intermediate surgical risk, transcatheter aortic valve replacement (TAVR) with a self-expanding supra-annular valve was noninferior to surgery for all-cause mortality or disabling stroke at 2 years. Comparisons of longer-term clinical and hemodynamic outcomes in these patients are limited.ObjectiveTo report prespecified secondary 5-year outcomes from the Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement (SURTAVI) randomized clinical trial.Design, Setting, and ParticipantsSURTAVI is a prospective randomized, unblinded clinical trial. Randomization was stratified by investigational site and need for revascularization determined by the local heart teams. Patients with severe aortic valve stenosis deemed to be at intermediate risk of 30-day surgical mortality were enrolled at 87 centers from June 19, 2012, to June 30, 2016, in Europe and North America. Analysis took place between August and October 2021.InterventionPatients were randomized to TAVR with a self-expanding, supra-annular transcatheter or a surgical bioprosthesis.Main Outcomes and MeasuresThe prespecified secondary end points of death or disabling stroke and other adverse events and hemodynamic findings at 5 years. An independent clinical event committee adjudicated all serious adverse events and an independent echocardiographic core laboratory evaluated all echocardiograms at 5 years.ResultsA total of 1660 individuals underwent an attempted TAVR (n = 864) or surgical (n = 796) procedure. The mean (SD) age was 79.8 (6.2) years, 724 (43.6%) were female, and the mean (SD) Society of Thoracic Surgery Predicted Risk of Mortality score was 4.5% (1.6%). At 5 years, the rates of death or disabling stroke were similar (TAVR, 31.3% vs surgery, 30.8%; hazard ratio, 1.02 [95% CI, 0.85-1.22]; P = .85). Transprosthetic gradients remained lower (mean [SD], 8.6 [5.5] mm Hg vs 11.2 [6.0] mm Hg; P < .001) and aortic valve areas were higher (mean [SD], 2.2 [0.7] cm2 vs 1.8 [0.6] cm2; P < .001) with TAVR vs surgery. More patients had moderate/severe paravalvular leak with TAVR than surgery (11 [3.0%] vs 2 [0.7%]; risk difference, 2.37% [95% CI, 0.17%- 4.85%]; P = .05). New pacemaker implantation rates were higher for TAVR than surgery at 5 years (289 [39.1%] vs 94 [15.1%]; hazard ratio, 3.30 [95% CI, 2.61-4.17]; log-rank P < .001), as were valve reintervention rates (27 [3.5%] vs 11 [1.9%]; hazard ratio, 2.21 [95% CI, 1.10-4.45]; log-rank P = .02), although between 2 and 5 years only 6 patients who underwent TAVR and 7 who underwent surgery required a reintervention.Conclusions and RelevanceAmong intermediate-risk patients with symptomatic severe aortic stenosis, major clinical outcomes at 5 years were similar for TAVR and surgery. TAVR was associated with superior hemodynamic valve performance but also with more paravalvular leak and valve reinterventions.
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| 15. |
- van Rheenen, W, et al.
(författare)
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Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology
- 2021
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 53:12, s. 1636-
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Tidskriftsartikel (refereegranskat)abstract
- Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons.
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