| 1. |
- Goldin, Lynn R., et al.
(författare)
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Elevated risk of chronic lymphocytic leukemia and other indolent non-Hodgkin's lymphomas among relatives of patients with chronic lymphocytic leukemia
- 2009
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 94:5, s. 647-653
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Tidskriftsartikel (refereegranskat)abstract
- Background Previous Studies have shown increased familial risk for chronic lymphocytic leukemia. In the most comprehensive study to date, we evaluated risk of chronic lymphocytic leukemia and lymphoproliferative disorders among First-degree relatives of chronic lymphocytic leukemia cases compared to first-degree relatives of controls. Design and Methods Population-based registry data from Sweden were used to evaluate outcomes in 26,947 first-degree relatives of 9,717 chronic lymphocytic leukemia patients (diagnosed 19583 8,159 matched controls. Using a 2004) compared with 107,223 first-degree relatives of 1 as marginal survival model, we calculated relative risks (RR) and 95% confidence intervals measures of Familial aggregation. Results Compared to relatives of controls, relatives of chronic lymphocytic leukemia patients had an increased risk for chronic lymphocytic leukemia (RR=8.5, 6.1-11.7) and other non-Hodkin's lymphomas (NHLs) (RR=1.9, 1.5-2.3). Evaluating NHL subtypes, we found a striking excess of indolent B-cell NHL specifically lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia and hairy cell leukemia. No excesses of aggressive B-cell or T-cell lymphomas were found. There was no statistical excess of Hodgkin's lymphoma, multiple myeloma, or the precursor condition, monoclonal gammopathy of undetermined significance, among chronic lymphocytic leukemia relatives. Conclusions These familial aggregations are striking and provide novel clues to research designed to uncover early pathogenetic mechanisms in chronic lymphocytic leukemia including studies to identify germ line susceptibility genes. However, clinicians should counsel their chronic lymphocytic leukemia patients emphasizing that because the baseline population risks are low, the absolute risk for a first-degree relative to develop chronic lymphocytic leukemia or another indolent lymphoma is low. At this time, an increased medical surveillance of first-degree relatives of chronic lymphocytic leukemia patients has no role Outside research studies.
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| 2. |
- Goldin, Lynn R., et al.
(författare)
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Highly increased familial risks for specific lymphoma subtypes
- 2009
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 146:1, s. 91-94
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Tidskriftsartikel (refereegranskat)abstract
- P>Studies have shown that familial risk contributes to aetiology of lymphomas. Using large population registries from Sweden, we evaluated risk of lymphoma subtypes among first-degree relatives of 2668 follicular lymphoma (FL) patients, 2517 diffuse large B-cell lymphoma (DLBCL) patients, and 6963 Hodgkin lymphoma (HL) patients compared to first-degree relatives of controls. Relatives were at the highest risk for developing the same lymphoma subtype as the case. DLBCL was increased 10-fold among relatives of DLBCL patients, FL was increased fourfold among relatives of FL patients and HL was increased fourfold among relatives of HL patients. These results imply that germline susceptibility genes are specific to lymphoma subtype.
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| 3. |
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| 4. |
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| 5. |
- Kristinsson, Sigurdur Y., et al.
(författare)
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Autoimmunity and risk for Hodgkin's lymphoma by subtype
- 2009
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 94:10, s. 1468-1469
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 6. |
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| 7. |
- Kristinsson, Sigurdur Y., et al.
(författare)
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Genetic and immune-related factors in the pathogenesis of lymphoproliferative and plasma cell malignancies
- 2009
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 94:11, s. 1581-1589
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Forskningsöversikt (refereegranskat)abstract
- There are data to support a role for genetic and immune-related factors in the pathogenesis of lymphomas and plasma cell diseases. In this paper, we review our published large population-based studies and other relevant studies in Hodgkin's and non-Hodgkin's lymphomas, multiple myeloma, and the precursor condition monoclonal gammopathy of undetermined significance. We discuss the overlap in risk factors between related malignancies and explore the underlying mechanisms. Based on these studies, we provide clinical implications and discuss the relevance of these data for patient counseling and clinical follow-up. Finally, we suggest future directions for new studies designed to increase our current knowledge and to define underlying biological mechanisms of our findings.
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| 8. |
- Kristinsson, Sigurdur Y., et al.
(författare)
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Genetics- and Immune-Related Factors in the Pathogenesis of Lymphoplasmacytic Lymphoma/Waldenstrom's Macroglobulinemia
- 2009
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Ingår i: Clinical Lymphoma & Myeloma. - 1557-9190. ; 9:1, s. 23-26
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Konferensbidrag (refereegranskat)abstract
- There are emerging data to support a role for genetic and immune-related factors in the pathogenesis of lymphoplasmacytic lymphoma/Waldenstrom's macroglobulinemia. In this article, we review our recently published, large, population-based studies using data from Sweden and from United States veterans and propose mechanisms and pathways underlying our observations. We also discuss future directions for new studies designed to increase our current knowledge and to define underlying biologic mechanisms of our findings. Finally, based on novel insights on this topic, we discuss clinical implications and provide perspective on the relevance of these data for patient counseling and clinical follow-up.
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| 9. |
- Kristinsson, Sigurdur Y, et al.
(författare)
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Patterns of hematologic malignancies and solid tumors among 37,838 first-degree relatives of 13,896 patients with multiple myeloma in Sweden.
- 2009
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 125:9, s. 2147-2150
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Tidskriftsartikel (refereegranskat)abstract
- There are emerging data to suggest a role for genetic factors in the pathogenesis of multiple myeloma (MM). Based on small numbers, certain solid tumors have been reported to occur more frequently among blood relatives of patients with MM. Using population-based data, we assessed risks for hematologic malignancies, monoclonal gammopathy of undetermined significance (MGUS), and solid tumors among first-degree relatives of patients with MM. We included 13,896 patients with MM and 54,365 matched controls. Also we identified first-degree relatives of patients with MM (n = 37,838) and controls (n = 151,068). Using a marginal survival model, we estimated relative risks (RRs) and 95% confidence intervals (CIs) for hematologic and solid tumors among family members of patients with MM and controls as measures of familial aggregation. Compared with relatives of controls, relatives of patients with MM had an increased risk of developing MM (RR = 2.1; 95% CI 1.6-2.9), MGUS (2.1; 1.5-3.1), acute lymphoblastic leukemia (ALL) (2.1; 1.0-4.2), any solid tumor (1.1; 1.0-1.1) and bladder cancer (1.3; 1.0-1.5). No significantly increased risk was found for other hematologic or solid malignancies. Our findings support a role for a shared susceptibility (genetic, environmental or both) that predisposes to MM, MGUS, ALL and bladder cancer.
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| 10. |
- Kristinsson, Sigurdur Y, et al.
(författare)
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Patterns of survival and causes of death following a diagnosis of monoclonal gammopathy of undetermined significance. A population-based study.
- 2009
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Ingår i: Haematologica. - : Ferrata Storti Foundation. - 0390-6078 .- 1592-8721. ; 94:12, s. 1714-1720
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: There are limited data on survival patterns among patients with monoclonal gammopathy of undetermined significance. DESIGN AND METHODS: We compared the survival of 4,259 patients with monoclonal gammopathy of undetermined significance, collected from hematology outpatient units in Sweden, with the survival of the general population by computing relative survival ratios. We also compared causes of death in these patients with those in 16,151 matched controls. RESULTS: One-, 5-, 10-, and 15-year relative survival ratios were 0.98 (95% CI 0.97-0.99), 0.93 (0.91-0.95), 0.82 (0.79-0.84), and 0.70 (0.64-0.76), respectively. Younger age at diagnosis of the gammopathy was associated with a significantly lower excess mortality compared to that in older patients (p<0.001). The excess mortality among patients with gammopathy increased with longer follow-up (p<0.0001). IgM (versus IgG/A) gammopathy was associated with a superior survival (p=0.038). Patients with monoclonal gammopathy of undetermined significance had an increased risk of dying from multiple myeloma (hazards ratio (HR)=553; 95% CI 77-3946), Waldenström's macroglobulinemia (HR=infinity), other lymphoproliferative malignancies (6.5; 2.8-15.1), other hematologic malignancies (22.9; 8.9-58.7), amyloidosis (HR=infinity), bacterial infections (3.4; 1.7-6.7), ischemic heart disease (1.3; 1.1-1.4), other heart disorders (1.5; 1.2-1.8), other hematologic conditions (6.9; 2.7-18), liver (2.1; 1.1-4.2), and renal diseases (3.2; 2.0-4.9). CONCLUSIONS: Our finding of decreased life expectancy in patients with monoclonal gammopathy of undetermined significance, which was most pronounced in the elderly and explained by both malignant transformation and non-malignant causes, is of importance in the understanding and clinical management of this disease. The underlying mechanisms may be causally related to the gammopathy, but may also be explained by underlying disease that led to the detection of the hematologic disease. Our results are of importance since they give a true estimation of survival in patients with monoclonal gammopathy of undetermined significance diagnosed in clinical practice.
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