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.

Migrainous Disorder and its Relation to Migraine Without Aura and Migraine with Aura. A Genetic Epidemiological Study

Cephalalgia ◽  
1996 ◽  
Vol 16 (6) ◽  
pp. 431-435 ◽  
Author(s):  
MB Russell ◽  
J Olesen
Keyword(s):  
Migraine With Aura ◽  
Migraine Without Aura ◽  
International Headache Society ◽  
Large Population ◽  
Population Based ◽  
Population Based Study ◽  
Female Ratio ◽  
First Degree Relatives ◽  
Increased Risk ◽  
Male Female Ratio

Migrainous disorder was analysed in a large population-based study of 4000 forty-year-old males and females. All interviews were conducted by one physician and the diagnostic criteria of the International Headache Society were used. Of the 48 people with migrainous disorder, 40 had migrainous disorder without aura and 9 had migrainous disorder with aura One person had co-occurrence of migrainous disorder with and without aura. The lifetime prevalence of migrainous disorder was 2.5% with a male: female ratio of 1:1.2. The first-degree relatives of probands with migrainous disorder were blindly interviewed. Compared with the general population, first-degree relatives of probands with migrainous disorder without aura had a slightly but less increased risk of migraine without aura than first-degree relatives of probands with migraine without aura. First-degree relatives of probands with migrainous disorder with aura had no increased risk of migraine with aura. We conclude that migrainous disorder without aura in some people is a type of migraine without aura and in other people not. Migrainous disorder with aura may be unrelated to migraine with aura. œ

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.

Peripheral Neuropathy in MGUS and Progression to Amyloid Light-Chain Amyloidosis: A Population-Based Study Including 15,351 MGUS Cases

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5444-5444
Author(s):  
Sæmundur Rögnvaldsson ◽  
Ingemar Turesson ◽  
Magnus Björkholm ◽  
Ola Landgren ◽  
Sigurður Yngvi Kristinsson
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Large Population ◽  
Diagnostic Delay ◽  
Population Based ◽  
Lymphoproliferative Disorders ◽  
First Year ◽  
Advisory Committees ◽  
Population Based Study ◽  
Increased Risk

Introduction Peripheral neuropathy (PN) is a common disorder that can be caused by amyloid light-chain amyloidosis (AL). AL is a rare disorder caused by the deposition of amyloid fibers, originating from malignant plasma cells. Amyloid deposition in peripheral nerves causes PN and is present in 35% of patients with newly diagnosed AL. Diagnosis of AL can be difficult, leading to under-recognition, diagnostic delay, and delayed treatment. Virtually all instances of AL are preceded by monoclonal gammopathy of undetermined significance (MGUS). MGUS is relatively common with a reported prevalence of 4.2% in the general Caucasian population over the age of 50 years. Although MGUS is usually considered asymptomatic, a significant proportion of affected individuals develop PN. However, we are not aware of any studies assessing how PN affects risk of MGUS progression to AL. We were therefore motivated to conduct a large population-based study including 15,351 Swedish individuals with MGUS diagnosed 1986-2013. Methods Participants diagnosed with MGUS between 1986-2013 were recruited from a registry of a nationwide network of hematology- and oncology centers and the Swedish Patient Registry. We then cross-linked data on recorded diagnoses of AL and PN from the Swedish Patient Registry, diagnoses of lymphoproliferative disorders form the Swedish Cancer Registry, and dates of death from the Cause of Death Registry to our study cohort. Individuals with a previous history of other lymphoproliferative disorders were excluded from the study. A multi-state survival model was created. At inclusion, participants started providing person time into the PN or the non-PN states depending on whether they had a previous diagnosis of PN. Those with MGUS who developed PN after inclusion were included into the PN state at the time of PN diagnosis and provided person time in the PN state after that. We then created a Cox proportional hazard regression model with AL as the endpoint. Participants were censored at diagnosis of other lymphoproliferative disorders. We adjusted for sex, age, and year of MGUS diagnosis. Results We included 15,351 participants with MGUS. Of those, 996 participants provided person-time with PN (6.5%). About half of those had PN at MGUS diagnosis (55%). A total of 174 cases of AL were recorded, with AL being more common among those who had PN (2.1% vs 1.0% p=0.002). Those who had PN had a 2.3-fold increased risk of AL as compared to those who did not have PN (hazard ratio (HR): 2.3; 95% confidence interval (95% CI): 1.5-3.7; p<0.001). The results were similar for those who had PN at MGUS diagnosis and those who did not. More than half of AL cases (53%) were diagnosed within one year after MGUS diagnosis. The rate was even higher among those with PN, with 82% of AL cases among those who presented with PN being diagnosed within one year after MGUS diagnosis. In the first year after inclusion, the incidence of AL was 15.2 and 6.1 per 1000 person-years for participants with and without PN respectively (HR: 1.8; 95% CI:1.0-3.4; p=0.04). Participants with PN continued to have an increased risk of progression to AL after the first year with an incidence of AL of 2.6 per 1000 person-years as compared to 1.1 per 1000 person-years among participants who did not have PN (HR:2.4; 95% CI: 1.1-5.0; p=0.02) (Figure). Discussion In this large population-based study, including 15,351 individuals with MGUS, we found that individuals with MGUS who develop PN have an increased risk of progression to AL. In fact, individuals with MGUS who have PN at MGUS diagnosis might already have AL. This risk of AL was highest during the first year after MGUS diagnosis with participants with PN having a higher risk than those who did not have PN. PN continued to be associated with a higher risk of MGUS progression to AL throughout the study period. This is the largest study that we are aware of assessing the association of PN and MGUS progression to AL. Since this is a registry-based study based on recorded diagnoses, some clinical data, including MGUS isotype, is not available. These findings suggest that increased awareness of PN as a feature of MGUS might decrease diagnostic delay and improve outcomes for patients with AL. Figure Disclosures Landgren: Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Theradex: Other: IDMC; Adaptive: Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Other: IDMC; Abbvie: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Multiple Myeloma and Infections: A Population-Based Study Based On 9,610 Multiple Myeloma Patients

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 945-945
Author(s):  
Cecilie Blimark ◽  
Ulf-Henrik Mellqvist ◽  
Ola Landgren ◽  
Magnus Björkholm ◽  
Malin L Hultcrantz ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bacterial Infections ◽  
Viral Infections ◽  
Normal Population ◽  
Large Population ◽  
Population Based ◽  
First Year ◽  
Population Based Study ◽  
Prophylactic Measures ◽  
Increased Risk

Abstract Abstract 945 Background Infections are a major cause of morbidity and mortality in patients with multiple myeloma (MM). No large population-based evaluation has been made to assess the risk of infections in MM patients compared to the normal population. Therefore, we performed a large study, using population-based data from Sweden, to estimate the risk of bacterial and viral infections among 9,610 MM patients compared to 37,718 matched controls. Methods We gathered information on all MM patients reported to the nationwide Swedish Cancer Registry from 1988 to 2004, with follow-up to 2007. For each MM patient, four population-based controls (matched by age, sex, and county of residence) were identified randomly from the Swedish population database. Information on occurrence and date of infections was obtained from the centralized Swedish Patient registry that captures information on individual patient-based discharge diagnosis from inpatient (with very high coverage) and outpatient care (since 2000). Cox proportional hazard models were used to estimate the overall, one- and five-year risk of infections. In addition, the effect of gender, age and calendar period of diagnosis was evaluated. Hazard ratios (HRs) and confidence intervals (CIs) were calculated for the occurrence of different infections. Results Overall, MM patients had a 6-fold (HR= 5.9; 95% CI=5.7-6.1) risk of developing any infection compared to matched controls (Figure). The increased risk of developing a bacterial infection was 6-fold (HR=5.9; 95%; CI=5.6-6.1), and for viral infections 9-fold (HR=9.0; 95% CI=8.0-10.1), compared to controls. More specifically, MM patients had an increased risk (p<0.05) of the following bacterial infections: cellulitis (HR=2.6; 95% CI =2.2-3.1), osteomyelitis (HR=3.0; 95% CI 2.0–4.4), endocarditis (HR=4.4; 95% CI 2.9–6.6), meningitis (HR=14.5; 95% CI 9.1–23.0), pneumonia (HR=6.2; 95% CI 5.9–6.5), pyelonephritis (HR=2.5; 95% CI 2.1–3.0), and septicaemia (HR=13.7; 95% CI 12.5–14.9) and for the viral infections influenza (HR=5.4; 95% CI 4.4–6.7) and herpes zoster (HR=12.8; 95% CI 10.5–15.5). The risk of infections was highest during the first year after diagnosis; the risk of bacterial infections was 11-fold (95% CI 10.7–12.9) and the risk of viral infections was 18-fold (95% CI 13.5–24.4) higher compared to controls during the first year after diagnosis. MM patients diagnosed in the more recent calendar periods had significantly higher risk of infections, reflected in a 1.6-fold (95% CI=1.5-1.7) and 2-fold (95% CI=1.9-2.1) increased risk in patients diagnosed during 1994–1999 and 2000–2004, compared to patients diagnosed 1986–1993. Females had a significantly lower risk of infections compared to males (p<0.001). Increasing age was significantly associated with a higher risk of infections (p<0.001). Discussion In this large population-based study including over 9,000 MM patients and 35,000 matched controls, we found that bacterial and viral infections represent a major threat to myeloma patients. We found the risk of specific infections like pneumonia, and septicemia to be over ten times higher in patients than in controls during the first year after MM diagnosis. Importantly, the risk of infections increased in more recent years. The effect on infectious complications due to novel drugs in the treatment of MM needs to be established and trials on prophylactic measures are required. Disclosures: Mellqvist: Janssen, Celgene: Honoraria.

scholarly journals Risk of Immune Thrombocytopenia Induced By Influenza Vaccine. a Nationwide Population-Based Study in France

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1086-1086
Author(s):  
Margaux Lafaurie ◽  
Bérangère Baricault ◽  
Maryse Lapeyre-Mestre ◽  
Laurent Sailler ◽  
Agnès Sommet ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Influenza Vaccination ◽  
Research Funding ◽  
Case Series ◽  
Population Based ◽  
Case Control ◽  
Population Based Study ◽  
Case Series Study ◽  
Increased Risk ◽  
Series Study

Introduction: Epidemiological studies suggest a risk of immune thrombocytopenia (ITP) following viral infections, particularly influenza. Conversely, an increased risk of ITP following vaccination has been proven for some vaccines like Measles-Mumps-Rubella vaccine. However, the risk of ITP induced by influenza vaccine is debated. Two case-controls studies has been conducted, with contradictory results: in the Berlin Case-Control Surveillance Study, an increased risk has been found (odds ratio - OR: 3.8 [95% confidence interval - CI: 1.5- 9.1]. Conversely, the French PGRx study suggested the absence of risk of ITP after influenza vaccination [OR: 0.9; 95% CI: 0.4-2.1]. These studies were limited by the number of ITP patients included (169 and 198, respectively) and other limitations. Therefore, we aimed to assess the risk of ITP induced by influenza vaccine in a nationwide cohort in France. Methods: We conducted a population-based study in France within the FAITH cohort (NCT03429660). This cohort is built within the National Health Database that links sociodemographic, hospital and out-hospital data. The FAITH cohort includes all adult patients with incident ITP in France since 2009. Patients are identified using a validated algorithm combining diagnosis codes and drug exposures (with very high positive predictive values). We included in the present study all patients with incident primary ITP aged ≥65 years at ITP diagnosis (indication of influenza vaccination in the general population in France) between July 2009 and June 2015. We assessed the link between influenza vaccine and ITP onset using two designs: a case-control and a self-controlled case series designs. In the case-control design, ITP cases were matched with four controls from the general population for age, sex and place of residency. Index dates for controls were similar to index dates of their matched cases. Cases and controls were compared for exposure to influenza vaccine in the 6 weeks before the index date using conditional logistic regression models adjusted for exposure to other drugs known as inducers of ITP. In the self-controlled case series study, only vaccinated ITP cases were included. The analysis compared the incidence of ITP within periods of risk (6 weeks following vaccination) to the incidence of ITP within other periods of time. We further excluded the 2 weeks prior to vaccine dispensing from the analysis to address selective survival bias (healthy vaccinee effect). Incidence rate ratios (IRRs) adjusted for seasonality were calculated. Results: We included 3,142 incident primary ITP patients aged ≥65 years matched with 12,528 controls in the case-control study. Overall, 147 cases (4.7%) and 579 controls (4.6%) were vaccinated with influenza vaccine during the 6 weeks prior to the index date (adjusted OR: 0.99; 95% CI: 0.80-1.23]). In the self-controlled case series study, 1,875 vaccinated ITP cases were included. Among them, 146 (7.8%) patients were diagnosed for ITP during one of the risk periods following vaccination. The adjusted IRR was 0.96 [95 CI%: 0.80-1.17]. Conclusion: This nationwide population-based study using two different designs showed no increased risk of ITP after influenza vaccination. Disclosures Moulis: Novartis pharma: Research Funding, Speakers Bureau; Amgen pharma: Research Funding, Speakers Bureau; CSL Behring: Research Funding.

scholarly journals Success Story of Targeted Therapy in Chronic Myeloid Leukemia: A Population-Based Study of Patients Diagnosed in Sweden From 1973 to 2008

2011 ◽  
Vol 29 (18) ◽  
pp. 2514-2520 ◽  
Author(s):  
Magnus Björkholm ◽  
Lotta Ohm ◽  
Sandra Eloranta ◽  
Åsa Derolf ◽  
Malin Hultcrantz ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Large Population ◽  
Age Groups ◽  
Relative Survival ◽  
The Elderly ◽  
Population Based ◽  
Population Based Study ◽  
First Line Therapy

Purpose Chronic myeloid leukemia (CML) management changed dramatically with the development of imatinib mesylate (IM), the first tyrosine kinase inhibitor targeting the BCR-ABL1 oncoprotein. In Sweden, the drug was approved in November 2001. We report relative survival (RS) of patients with CML diagnosed during a 36-year period. Patients and Methods Using data from the population-based Swedish Cancer Registry and population life tables, we estimated RS for all patients diagnosed with CML from 1973 to 2008 (n = 3,173; 1,796 males and 1,377 females; median age, 62 years). Patients were categorized into five age groups and five calendar periods, the last being 2001 to 2008. Information on use of upfront IM was collected from the Swedish CML registry. Results Relative survival improved with each calendar period, with the greatest improvement between 1994-2000 and 2001-2008. Five-year cumulative relative survival ratios (95% Cls) were 0.21 (0.17 to 0.24) for patients diagnosed 1973-1979, 0.54 (0.50 to 0.58) for 1994-2000, and 0.80 (0.75 to 0.83) for 2001-2008. This improvement was confined to patients younger than 79 years of age. Five-year RSRs for patients diagnosed from 2001 to 2008 were 0.91 (95% CI, 0.85 to 0.94) and 0.25 (95% CI, 0.10 to 0.47) for patients younger than 50 and older than 79 years, respectively. Men had inferior outcome. Upfront overall use of IM increased from 40% (2002) to 84% (2006). Only 18% of patients older than 80 years of age received IM as first-line therapy. Conclusion This large population-based study shows a major improvement in outcome of patients with CML up to 79 years of age diagnosed from 2001 to 2008, mainly caused by an increasing use of IM. The elderly still have poorer outcome, partly because of a limited use of IM.

The risk of debilitating falls in Manitobans living with prostate cancer (pc).

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 244-244
Author(s):  
Joel Roger Gingerich ◽  
Pascal Lambert ◽  
Malcolm Doupe ◽  
Paul Joseph Daeninck ◽  
Marshall W. Pitz ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Cumulative Incidence ◽  
Large Population ◽  
Univariate Analysis ◽  
Population Based ◽  
Community Dwelling ◽  
Low Grade ◽  
Population Based Study ◽  
Increased Risk

244 Background: Falls and fall-related injuries are important patient safety problems. Some studies suggest that pc patients have higher fall rates, however the severity of these falls is unknown. We sought to measure if pc patients are at increased risk of a debilitating fall requiring hospitalization. Methods: This is a retrospective population-based study utilizing the Manitoba Cancer Registry and Manitoba Health administrative databases. Our cohort consists of all community-dwelling patients living in Manitoba Canada who were diagnosed with pc between 2004 and 2008. These individuals were matched by age, sex, and time of diagnosis with up to three cancer-free controls. Debilitating falls were defined as falls/fractures requiring hospitalization and were identified using ICD-9 and -10 billing codes. A competing risk model was used to compare debilitating falls between the pc and cancer-free cohorts and expressed as sub-hazard ratios. Follow-up ended December 31, 2009. Results: 2,903 pc patients were identified along with 8,686 matched controls. The mean age was 69.3 and 68.8 respectively. The median follow-up was 3.05 years. Debilitating falls were identified in 109 patients (3.8%) with pc and 345 (4%) matched controls. The cumulative incidence of debilitating falls for those with pc vs cancer-free controls were: 1.08% vs. 1.13% at 1-year and 5.25% vs. 5.96% at five years of follow-up (SHR = 0.95, 95% CI = 0.77 – 1.18, p = 0.65). On univariate analysis, patients with stage IV pc were at higher risk of falls compared to matched controls. This difference was not significant on multivariate analysis though (SHR = 1.19, 95% CI = 0.74 – 1.89, p = 0.48). On multivariate analysis, patients with a Gleason score of ≤6 experienced a reduced risk of debilitating falls compared to matched controls (SHR = 0.44, 95% CI = 0.27 – 0.72, p = 0.001), whereas patients with other Gleason scores did not. The analysis was similar when patients with fractures were excluded. Conclusions: In this large population-based study, the 1- and 5-year cumulative incidence of debilitating falls did not differ significantly for patients with vs without pc. In fact, compared to matched controls, low grade pc patients were less likely to experience a debilitating fall.

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 Acute Myeloid Leukemia and Myelodysplastic Syndromes

2012 ◽  
Vol 30 (2) ◽  
pp. 179-183 ◽  
Author(s):  
Lynn R. Goldin ◽  
Sigurdur Y. Kristinsson ◽  
Xueying Sharon Liang ◽  
Åsa R. Derolf ◽  
Ola Landgren ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndromes ◽  
Myeloid Leukemia ◽  
Myeloproliferative Neoplasms ◽  
Familial Aggregation ◽  
Young Patients ◽  
Myeloid Malignancies ◽  
First Degree Relatives ◽  
Increased Risk ◽  
Acute Myeloid

Purpose Apart from rare pedigrees with multiple cases of acute myeloid leukemia (AML), there is limited data on familial aggregation of AML and myelodysplastic syndromes (MDSs) in the population. Patients and Methods Swedish population-based registry data were used to evaluate risk of AML, MDS, and other malignancies among 24,573 first-degree relatives of 6,962 patients with AML and 1,388 patients with MDS compared with 106,224 first-degree relatives of matched controls. We used a marginal survival model to calculate familial aggregation. Results AML and/or MDS did not aggregate significantly in relatives of patients with AML. There was a modest risk ratio (RR, 1.3; 95% CI, 0.9 to 1.8) in myeloproliferative/myeloid malignancies combined. The risks for any hematologic or any solid tumor were modestly but significantly increased. Relatives of patients with MDS did not show an increased risk for any hematologic tumors. In contrast, we found a significantly increased risk (RR, 6.5; 95% CI, 1.1 to 38.0) of AML/MDS and of all myeloid malignancies combined (RR, 3.1; 95% CI, 1.0 to 9.8) among relatives of patients diagnosed at younger than age 21 years. Conclusion We did not find evidence for familial aggregation of the severe end of the spectrum of myeloid malignancies (AML and MDS). The risks of myeloproliferative neoplasms were modestly increased with trends toward significance, suggesting a possible role of inheritance. In contrast, although limited in sample size, relatives of young patients with AML were at increased risk of AML/MDS, suggesting that germline genes may play a stronger role in these patients. The increased risk of all hematologic malignancies and of solid tumors among relatives of patients with AML suggests that genes for malignancy in general and/or other environmental factors may be shared.

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