444 research outputs found
Medical history and lifestyle factors have limited impact on time-to-first-treatment in patients with chronic lymphocytic leukemia
No full textBackground Chronic lymphocytic leukemia (CLL) is a heterogeneous disease. Whereas some patients have an indolent disease, others experience an aggressive course and early death. Our aim was to investigate if modifiable and non-modifiable medical history and lifestyle factors prior to diagnosis had an impact on the natural course of the disease. Method In 1154 CLL patients, we assessed if the weight, physical activity, smoking, and alcohol consumption or non-modifiable characteristics including family history of lymphoid malignancy and medical history were associated with time-to-first-treatment (TTFT) and adjusted all results for the CLL-International Prognostic Index (CLL-IPI). Results TTFT was shorter for patients with high/very high-risk CLL-IPI than those with low/intermediate risk CLL-IPI. In the adjusted analysis we did not find additional impact on TTFT besides CLL-IPI from any environmental characteristics assessed. Conclusions We found limited impact of environmental factors on the natural course of CLL (measured as the TTFT in treatment na & iuml;ve patients) providing valuable knowledge, and potential relief, to share with patients at the time of diagnosis. How patients have lived their life (i.e. degree of physical activity, smoking and alcohol consumption) has no impact on the natural course of chronic lymphocytic leukemia (CLL), measured as time to first treatment, while CLL-international prognostic index (IPI) and its components strongly predicts prognosis. imageIngrid Glimelius and Geffen Kleinstern contributed equally to the first authorship and Susan L. Slager and Karin E. Smedby contributed equally to the last authorship.</p
Familial CLL: Genes and Environment
No full textHowever, the clinical implication of familial aggregation is minimal given the overall rarity of CLL. Linkage studies have been conducted in high-risk CLL families to screen the whole genome for loci that contribute to susceptibility, but no gene mutations have yet been identified by this method. Association studies of candidate genes have implicated immune function and other genes, but more studies are needed to verify these findings. The ability to conduct large-scale genomic studies will play an important role in detecting susceptibility genes for CLL over the next few years and thereby help to delineate etiologic pathways
Genome-wide linkage analysis of systolic blood pressure: a comparison of two approaches to phenotype definition
No full textAssociation of polygenic risk score with the risk of chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis
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An analytical framework for strategic delta planning: negotiating consent for long-term sustainable delta development
No full textSectoral planning on water, agriculture and urban development has not been able to prevent increased flood risks and environmental degradation in many deltas. Governments conceive strategic delta planning as a promising planning approach and develop strategic delta plans. Such plans are linked to actions and means for implementation in the short-term, in line with long-term strategic choices. This paper introduces an analytical framework that focuses on the role of actors, innovative solutions and participatory planning tools in negotiating consent for the strategic choices in a delta plan and its implementation. Cases of Bangladesh, the Netherlands and Vietnam are discussed as a plausibility probe to explore the framework's potential. The probe reveals that the framework is promising to explain the process and outcomes of strategic delta planning in urbanizing deltas. The paper ends with an initial research agenda to stimulate research and discussion on this new delta planning approach.Accepted Author ManuscriptPolicy Analysi
Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia
No full textChronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P=2.55 × 10−11), 6p25.2 (rs73718779, SERPINB6, P=1.97 × 10−8) and 3q28 (rs9815073, LPP, P=3.62 × 10−8), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P=1.00 × 10−11) in the combined analysis. We find suggestive evidence (P<5 × 10−7) for two additional new loci at 4q24 (rs10028805, BANK1, P=7.19 × 10−8) and 3p22.2 (rs1274963, CSRNP1, P=2.12 × 10−7). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility
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