scholarly journals Risk of lymphoproliferative disorders among first-degree relatives of lymphoplasmacytic lymphoma/Waldenström macroglobulinemia patients: a population-based study in Sweden

Blood ◽  
2008 ◽  
Vol 112 (8) ◽  
pp. 3052-3056 ◽  
Author(s):  
Sigurdur Y. Kristinsson ◽  
Magnus Björkholm ◽  
Lynn R. Goldin ◽  
Mary L. McMaster ◽  
Ingemar Turesson ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Familial Aggregation ◽  
Population Based ◽  
Lymphoproliferative Disorders ◽  
Lymphoplasmacytic Lymphoma ◽  
Degree Relative ◽  
Waldenström Macroglobulinemia ◽  
First Degree Relatives ◽  
Waldenstrom Macroglobulinemia ◽  
Increased Risk

Abstract A role for genetic factors in the etiology of lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM) is implicated based on prior findings from multiply affected families and small case-control and cohort studies. We identified 2144 LPL/WM patients (1539 WM [72%] and 605 LPL [28%]) diagnosed in Sweden, 8279 population-based matched controls, and linkable first-degree relatives of patients (n = 6177) and controls (n = 24 609). Using a marginal survival model, we calculated relative risks and 95% confidence intervals as measures of familial aggregation. We found first-degree relatives of LPL/WM patients to have 20-fold (4.1-98.4), 3.0-fold (2.0-4.4), 3.4-fold (1.7-6.6), and 5.0-fold (1.3-18.9) increased risks of developing LPL/WM, non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), and monoclonal gammopathy of undetermined significance (MGUS), respectively. However, there was no evidence of an increased risk of developing multiple myeloma or Hodgkin lymphoma. In analyses stratified by type of first-degree relative (parent, sibling, offspring), age at diagnosis of the probands (greater or less than 70 years), and sex of the first-degree relative, we did not observe the risk estimates to be significantly different compared with the overall analyses. Our findings of highly increased risks of developing LPL/WM, NHL, CLL, and MGUS support the operation of shared susceptibility genes that predispose to LPL/WM and other lymphoproliferative disorders.

scholarly journals Risk of plasma cell and lymphoproliferative disorders among 14621 first-degree relatives of 4458 patients with monoclonal gammopathy of undetermined significance in Sweden

Blood ◽  
2009 ◽  
Vol 114 (4) ◽  
pp. 791-795 ◽  
Author(s):  
Ola Landgren ◽  
Sigurdur Y. Kristinsson ◽  
Lynn R. Goldin ◽  
Neil E. Caporaso ◽  
Cecilie Blimark ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Monoclonal Gammopathy ◽  
Case Reports ◽  
Population Based ◽  
Lymphocytic Leukemia ◽  
Degree Relative ◽  
First Degree Relatives ◽  
Non Hodgkin Lymphoma ◽  
Increased Risk ◽  
Undetermined Significance

Abstract Familial clustering of the precursor condition, monoclonal gammopathy of undetermined significance (MGUS) has been observed in case reports and in smaller studies. Using population-based data from Sweden, we identified 4458 MGUS patients, 17505 population-based controls, and first-degree relatives of patients (n = 14621) and controls (n = 58387) with the aim to assess risk of MGUS and lymphoproliferative malignancies among first-degree relatives of MGUS patients. Compared with relatives of controls, relatives of MGUS patients had increased risk of MGUS (relative risk [RR] = 2.8; 1.4-5.6), multiple myeloma (MM; RR = 2.9; 1.9-4.3), lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM; RR = 4.0; 1.5-11), and chronic lymphocytic leukemia (CLL; RR = 2.0; 1.2-2.3). Relatives of patients with IgG/IgA MGUS had a 4.0-fold (1.7-9.2), 2.9-fold (1.7-4.9), and 20-fold (2.3-170) elevated risk of developing MGUS, MM, and LPL/WM, respectively. Relatives of IgM MGUS patients had 5.0-fold (1.1-23) increased CLL risk and nonsignificant excess MM and LPL/WM risks. The results were very similar when we assessed risk by type of first-degree relative, age at MGUS (above/below 65 years), or sex. Risk of non-Hodgkin lymphoma or Hodgkin lymphoma was not increased among MGUS relatives. Among first-degree relatives of a nationwide MGUS cohort, we found elevated risks of MGUS, MM, LPL/WM, and CLL, supporting a role for germline susceptibility genes, shared environmental influences, or an interaction between both.

scholarly journals Increased risks of polycythemia vera, essential thrombocythemia, and myelofibrosis among 24 577 first-degree relatives of 11 039 patients with myeloproliferative neoplasms in Sweden

Blood ◽  
2008 ◽  
Vol 112 (6) ◽  
pp. 2199-2204 ◽  
Author(s):  
Ola Landgren ◽  
Lynn R. Goldin ◽  
Sigurdur Y. Kristinsson ◽  
Elin A. Helgadottir ◽  
Jan Samuelsson ◽  
...  
Keyword(s):  
Polycythemia Vera ◽  
Essential Thrombocythemia ◽  
Myeloid Leukemia ◽  
Myeloproliferative Neoplasms ◽  
Familial Aggregation ◽  
Susceptibility Gene ◽  
Degree Relative ◽  
First Degree Relatives ◽  
Relative Risks ◽  
Increased Risk

Abstract Previous small studies have reported familial clustering of myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF). We identified 6217 PV, 2838 ET, 1172 MF, and 812 MPN unclassifiable (NOS) patients diagnosed in Sweden, 43 550 controls, and first-degree relatives of cases (n = 24 577) and controls (n = 99 542). Using a marginal survival model, we calculated relative risks (RRs) and 95% confidence intervals as measures of familial aggregation. Relatives of MPN patients had significantly increased risks of PV (RR = 5.7; 3.5-9.1), ET (RR = 7.4; 3.7-14.8), and MPN NOS (RR = 7.5; 2.7-20.8). Analyses stratified by type of first-degree relative revealed consistently higher risks for siblings, compatible with a model of recessive genetic inheritance, which can be confirmed only by identifying the susceptibility gene(s). Mean age at MPN diagnosis was not different (P = .20) for affected relatives of cases (57.5 years) versus controls (60.6 years), and risk of MPN by age was not different for parents versus offspring of MPN cases (P = .10), providing no support for anticipation. Relatives of MPN patients had a borderline increased risk of chronic myeloid leukemia (CML; RR = 1.9; 0.9-3.8; P = .09). Our findings of 5- to 7-fold elevated risk of MPNs among first-degree relatives of MPN patients support the hypothesis that common, strong, shared susceptibility genes predispose to PV, ET, MF, and possibly CML.

scholarly journals Familial Aggregation of Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia with Solid Tumors and Myeloid Malignancies

2012 ◽  
Vol 127 (3) ◽  
pp. 173-177 ◽  
Author(s):  
Sigurdur Y. Kristinsson ◽  
Lynn R. Goldin ◽  
Ingemar Turesson ◽  
Magnus Björkholm ◽  
Ola Landgren
Keyword(s):  
Solid Tumors ◽  
Familial Aggregation ◽  
Lymphoplasmacytic Lymphoma ◽  
Waldenström Macroglobulinemia ◽  
Myeloid Malignancies ◽  
Waldenstrom Macroglobulinemia

Familial Aggregation of Multiple Myeloma and Its Precursor Monoclonal Gammopathy of Undetermined Significance (MGUS): A Population-Based Study in Sweden.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1678-1678
Author(s):  
Sigurdur Y Kristinsson ◽  
Magnus Bjorkholm ◽  
Lynn R. Goldin ◽  
Cecilie Blimark ◽  
Ulf-Henrik Mellqvist ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Hodgkin Lymphoma ◽  
Monoclonal Gammopathy ◽  
Familial Aggregation ◽  
Large Population ◽  
Population Based ◽  
Case Control ◽  
Population Based Study ◽  
First Degree Relatives ◽  
Undetermined Significance

Abstract Background: Evidence from multiply affected families, case-control and population-based registry studies implicate a role for genetic factors in multiple myeloma (MM). The aim of this large population-based familial case-control study was to quantify risks of MM, monoclonal gammopathy of undetermined significance (MGUS), and other lymphoproliferative disorders among first-degree relatives of MM patients. Methods: We identified 13,963 MM patients diagnosed in Swedish hospitals 1958–2005, with linkable relatives. Using the population-based central Population- and Multigenerational registries, we obtained 54,610 matched controls and first-degree relatives of MM patients (n=37,838) and controls (n=151,068). Relatives of MM patients and controls were linked with hospital-based outpatient registries and the central Swedish Cancer Registry to define occurrence of MGUS and lymphoproliferative malignancies. Measures of familial aggregation were calculated by a marginal survival model using relatives as the cohort. Results: First-degree relatives of MM patients had a significantly increased risk of developing MM [relative risk (RR)=2.1; (95% confidence interval (CI), 1.6–2.9)] and MGUS [2.1 (1.5–3.1)]. The risk estimates were very similar when we conducted analyses by gender of proband, by type of first-degree relative (parent, sibling, offspring), and by age at MM diagnosis (below/above 65 yrs) for probands. Among relatives of MM patients, we found no excess risk of chronic lymphocytic leukemia, non-Hodgkin lymphoma, Hodgkin lymphoma, or lymphoplasmacytic lymphoma/Waldenström’s macroglobulinemia. Conclusions: In this large population-based study, we found relatives of MM patients to have a 2-fold excess risk of developing MM and MGUS compared with relatives of controls. Our findings support the theory that there are common, shared susceptibility genes that predispose to MM and MGUS. Better characterization of early genetic lesions mediating monoclonal plasma-cell proliferation, survival, and migration in the bone marrow microenvironment will potentially provide clues to pathogenesis and allow identification of novel molecular targets.

Increased Risks of Polycythemia Vera (PV), Essential Thrombocythemia (ET), and Myelofibrosis (MF) among 24577 First-Degree Relatives of 11039 Patients with Chronic Myeloproliferative Disorders (MPD) in Sweden.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 680-680 ◽  
Author(s):  
Ola Landgren ◽  
Lynn R. Goldin ◽  
Sigurdur Y. Kristinsson ◽  
Jan Samuelsson ◽  
Magnus Bjorkholm
Keyword(s):  
Myeloid Leukemia ◽  
Familial Aggregation ◽  
Large Population ◽  
Case Series ◽  
Population Based ◽  
Local Hospital ◽  
Population Based Study ◽  
First Degree Relatives ◽  
Increased Risk ◽  
Familial Clustering

Abstract Background. Familial clustering of PV, ET, MF, and chronic myeloid leukemia (CML) has been reported through case reports and smaller case series. Recently, several studies reported that in families with multiple MPD patients, the JAK2 mutation is not an early germ line predisposing factor for MPD but rather a facilitator of proliferative advantages. However, the degree of familial clustering in the population has not been defined. We have conducted the first large population-based study to quantify risks of developing MPD and related malignancies in first-degree relatives of MPD patients. Methods. Using high-quality central population-based registries, we identified 6217 PV, 2838 ET, and 1984 MF patients diagnosed in Swedish hospitals 1958–2005 (Cancer and local hospital-based registries), with linkable relatives; 43550 frequency-matched controls (Population registry); and first-degree relatives of cases (n=24577) and controls (n=99542) (Multigenerational registry). Relatives of MPD patients and controls were linked with the Cancer and local hospital-based registries to define occurrence of MPD and other related neoplasms. We used a marginal survival model to calculate relative risks (RR) and 95% confidence intervals (CI) as measures of familial aggregation. Results. Compared with controls, relatives of MPD patients had significantly increased risks of PV (RR=5.70; 95% CI 3.55–9.14), ET (RR=7.37; 95% CI 3.67–14.81), and MF (RR=3.53; 95% CI 1.59–7.85). Risks were similar when we restricted the analyses to relatives of patients with the same MPD (PV-PV, ET-ET, and MF-MF) Also, risk-estimates were virtually the same for various types of first-degree relatives (parents, siblings, offspring); the same was true when we calculated risks by age at MPD of cases (above vs. below 65 yrs), and sex of relatives. Age at diagnosis of MPD was not different for case and control relatives. Furthermore, relatives of MPD patients (vs. controls) had a borderline increased risk of CML (RR=1.86; 95% CI 0.90–3.74; p=0.07). As expected, we found excess of subsequent acute myeloid leukemia (AML) (n=271; 2.5%) and myelodysplastic syndrome (MDS) (n=27; 0.2%) among MPD patients; however, there were no increased risks of AML or MDS among relatives of MPD patients. Conclusions. In this first large population-based study including more than 11000 MPD patients and their almost 25000 linkable first-degree relatives, we found 3- to 7-fold elevated risks of developing MPDs among first-degree relatives of MPD patients. Our results support the hypothesis that there are common, strong, shared susceptibility genes that predispose to PV, ET, MF, and possibly CML.

Increased Risk of Monoclonal Gammopathy of Undetermined Significance (MGUS) and Lymphoproliferative Tumors among 14689 First-Degree Relatives of 4488 MGUS Patients in Sweden.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 660-660
Author(s):  
Ola Landgren ◽  
Sigurdur Y. Kristinsson ◽  
Lynn R. Goldin ◽  
Neil E. Caporaso ◽  
Cecilie Blimark ◽  
...  
Keyword(s):  
Germ Line ◽  
Familial Aggregation ◽  
Age At Onset ◽  
Population Based ◽  
Excess Risk ◽  
Lymphocytic Leukemia ◽  
First Degree Relatives ◽  
Increased Risk ◽  
Swedish Cancer Registry ◽  
And Migration

Abstract Background. Evidence from multiply affected families, case-control and population-based registry studies implicate a role for genetic factors in multiple myeloma (MM). Previous studies based on small numbers have suggested excess risk of MGUS in relatives of MM patients. Aims of this large nationwide MGUS study were to quantify risks of developing MGUS and lymphoproliferative malignancies in first-degree relatives and to define characteristics of familial aggregation. Methods. We identified 4488 MGUS patients diagnosed in all major hematology/oncology outpatient units in Sweden (1967–2005), with linkable relatives. Using the population-based central Multigenerational Registry, we obtained 17628 frequency-matched controls and first-degree relatives of cases (n=14689) and controls (n=58698). Relatives of MGUS cases and controls were linked with hospital-based outpatient registries and the central Swedish Cancer Registry to define occurrence of MGUS and lymphoproliferative tumors. Measures of familial aggregation were calculated by a marginal survival model using relatives as the cohort. Results. Compared with controls, relative risk (RR) of MGUS was significantly increased (RR=2.84; 95% CI 1.45–5.57) in relatives of MGUS cases. Relatives of MGUS cases (vs. controls) also had excess risk of MM (RR=2.87; 95% CI 1.92–4.27), Waldenstrom’s macroglobulinemia (WM) (RR=4.94; 95% CI 1.32–18.46), and chronic lymphocytic leukemia (CLL) (RR=2.05; 95% CI 1.22–3.43). Risk-estimates were similar for various types of first-degree relatives (parents, siblings, offspring); the same was true when we estimated risks by age at MGUS of cases (above vs. below 65 yrs), and sex of relatives. Age at onset of MGUS and lymphoproliferative tumors was virtually the same for case and control relatives. There was no increased risk (RR∼1) of NHL or HL among relatives of MGUS cases. Conclusions. Among first-degree relatives of a large nationwide MGUS cohort in Sweden, we found 2- to 3-fold elevated risks of developing MGUS, MM, WM, and CLL. These results suggest the operation of shared common germ line susceptibility genes in the pathway to MGUS and certain lymphoproliferative tumors. Better characterization of early genetic lesions mediating monoclonal plasma-cell proliferation, survival, and migration in the bone marrow microenvironment will ultimately enhance our understanding of MGUS, MM, WM, and CLL pathophysiology, provide clues to etiology, and allow identification of novel molecular targets.

Risk and coaggregation of major psychiatric disorders among first-degree relatives of patients with bipolar disorder: a nationwide population-based study

2018 ◽  
Vol 49 (14) ◽  
pp. 2397-2404 ◽  
Author(s):  
Mu-Hong Chen ◽  
Ju-Wei Hsu ◽  
Kei-Lin Huang ◽  
Tung-Ping Su ◽  
Cheng-Ta Li ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Psychiatric Disorders ◽  
Population Based ◽  
Autism Spectrum ◽  
The Public ◽  
First Degree Relatives ◽  
Relative Risks ◽  
Dependent Relationship ◽  
Increased Risk ◽  
Bipolar Patients

AbstractBackgroundBipolar disorder is a highly heritable mental illness that transmits intergeneratively. Previous studies supported that first-degree relatives (FDRs), such as parents, offspring, and siblings, of patients with bipolar disorder, had a higher risk of bipolar disorder. However, whether FDRs of bipolar patients have an increased risk of schizophrenia, major depressive disorder (MDD), autism spectrum disorder (ASD), and attention deficit hyperactivity disorder (ADHD) remains unclear.MethodsAmong the entire population in Taiwan, 87 639 patients with bipolar disorder and 188 290 FDRs of patients with bipolar disorder were identified in our study. The relative risks (RRs) of major psychiatric disorders were assessed among FDRs of patients with bipolar disorder.ResultsFDRs of patients with bipolar disorder were more likely to have a higher risk of major psychiatric disorders, including bipolar disorder (RR 6.12, 95% confidence interval (CI) 5.95–6.30), MDD (RR 2.89, 95% CI 2.82–2.96), schizophrenia (RR 2.64, 95% CI 2.55–2.73), ADHD (RR 2.21, 95% CI 2.13–2.30), and ASD (RR 2.10, 95% CI 1.92–2.29), than the total population did. These increased risks for major psychiatric disorders were consistent across different familial kinships, such as parents, offspring, siblings, and twins. A dose-dependent relationship was also found between risk of each major psychiatric disorder and numbers of bipolar patients.ConclusionsOur study was the first study to support the familial coaggregation of bipolar disorder with other major psychiatric disorders, including schizophrenia, MDD, ADHD, and ASD, in a Taiwanese (non-Caucasian) population. Given the elevated risks of major psychiatric disorders, the public health government should pay more attention to the mental health of FDRs of patients with bipolar disorder.

Sign in / Sign up

Export Citation Format

Share Document