Personal and family history of immune-related conditions increase the risk of plasma cell disorders: a population-based study

Abstract The associations between immune-related conditions and multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) have previously been investigated with inconsistent results. In a large population-based study, we identified 19 112 patients with MM, 5403 patients with MGUS, 96 617 matched control subjects, and 262 931 first-degree relatives. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for the association of MM and MGUS with immune-related conditions by use of logistic regression. A personal history of all infections combined was associated with a significantly increased risk of MM (OR = 1.2; 95% CI, 1.1-1.3), and a personal history of all conditions in the categories infections (OR = 1.6; 95% CI, 1.5-1.7), inflammatory conditions (OR = 1.4; 95% CI, 1.2-1.5), and autoimmune diseases (OR = 2.1; 95% CI, 1.9-2.4) was associated with a significantly increased risk of MGUS. Several specific immune-related conditions elevated the risk of MM and/or MGUS. A family history of autoimmune disease was associated with a significantly increased risk of MGUS (OR = 1.1; 95% CI, 1.00-1.2), but not MM. Our findings suggest that immune-related conditions and/or their treatment are of importance in the etiology of MGUS and possibly MM. The association of both personal and family history of autoimmune disease with MGUS indicates the potential for shared susceptibility for these conditions.

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Family History of Venous Thromboembolism As a Risk Factor for Thrombosis in Multiple Myeloma Patients: A Population-Based Study,

Blood ◽

10.1182/blood.v118.21.3987.3987 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3987-3987

Author(s):

Sigurdur Y Kristinsson ◽

Lynn Goldin ◽

Ingemar Turesson ◽

Magnus Bjorkholm ◽

Ola Landgren

Keyword(s):

Multiple Myeloma ◽

Risk Factor ◽

Venous Thromboembolism ◽

Family History ◽

Large Population ◽

Population Based ◽

Population Based Study ◽

Increased Risk ◽

History Of ◽

The Impact

Abstract Abstract 3987 Background: Patients with multiple myeloma are at an increased risk of venous thromboembolism (VTE), especially when treated with thalidomide and lenalidomide. The etiology of this is largely unknown, but probably involves both genetic and environmental factors. Family history of VTE is a known risk factor for VTE in the general population, including known inherited thrombophilic abnormalities. The influence of a family history of VTE as a potential risk factor for VTE in multiple myeloma patients is unknown. To expand our knowledge on this topic, we conducted a large population-based study based on all multiple myeloma patients diagnosed in Sweden 1958–2004. Patients and Methods: We assessed the impact of family history of VTE as a risk factor for VTE among 21,067 multiple myeloma patients and 83,094 matched controls. Data on multiple myeloma patients was gathered from the Swedish Cancer Registry, information on first-degree relatives from the national Multigenerational Registry, and occurrence of VTE from the nationwide Patient Registry. We calculated odds ratios (OR) and 95% confidence intervals (CI) using chi-square. Results: Of the 21,067 multiple myeloma patients included in the study (54% males, median age at diagnosis 71 years), 66% had an identifiable first-degree relative. VTE was diagnosed in 1,429 multiple myeloma patients, and 921 had a family history of VTE. Compared to multiple myeloma patients without a family history of VTE, multiple myeloma patients with a family history of VTE had a 2.2-fold (95% CI 1.8–2.7; p<0.001) higher risk of VTE. Among 4,986 controls that were diagnosed with VTE, 316 had a family history of VTE. Controls with a family history of VTE had a 1.5-fold (95% CI 1.3–1.7; p<0.001) increased risk of VTE compared to controls without a family history of VTE. The difference of the impact of family history of VTE on the risk of VTE in multiple myeloma patients versus controls was significant. Summary and Conclusions: In this large population-based study including more than 20,000 multiple myeloma patients, we found family history of VTE to have a larger impact on VTE risk in multiple myeloma than in matched controls. Our findings confirm that genetic factors contribute to thrombophilia in multiple myeloma and may have therapeutic implications regarding thromboprophylaxis and treatment. Disclosures: No relevant conflicts of interest to declare.

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Family History Of Hematologic Malignancies and Disorders In a Population Based Study Of Myelodysplastic Syndromes (MDS)

Blood ◽

10.1182/blood.v122.21.1541.1541 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1541-1541

Author(s):

Angela R. Smith ◽

Erica D. Warlick ◽

Rachel K. Fonstad ◽

Michelle A. Roesler ◽

Jenny N. Poynter ◽

...

Keyword(s):

Family History ◽

Conflicts Of Interest ◽

Positive Family History ◽

Hematologic Malignancies ◽

Population Based ◽

Newly Diagnosed ◽

Population Based Study ◽

Hematopoietic Stem ◽

Increased Risk ◽

History Of

Abstract Background MDS is a clonal hematopoietic stem cell disorder characterized by dysplastic changes in the bone marrow, ineffective hematopoiesis and an increased risk for developing acute myeloid leukemia (AML). The majority of MDS cases are sporadic, but rare familial cases have been described and are often ascertained through clinic-based referrals. To our knowledge, no population based study of MDS has examined the frequency of family history of hematologic malignancies and disorders in patients, nor associations with disease characteristics and outcomes. Methods Newly diagnosed MDS cases are being identified by rapid case ascertainment by the Minnesota Cancer Surveillance System (MCSS), a population-based cancer registry in Minnesota. Eligibility criteria include all newly diagnosed cases of MDS during the period April 1, 2010-October 31, 2014, between 20-85 years, Minnesota resident, and ability to understand English or Spanish. Proxy interviews are not being conducted. Medical records and biologic samples are obtained and questionnaires are filled out by participants. Centralized pathology and cytogenetics review confirm diagnosis and classify by subtype and risk score including the Revised International Prognostic Scoring System (IPSS-R). Since 2010, information on family history has been obtained through questionnaire responses and/or medical record review on 353 MDS patients. Cases were considered to have a positive family history if they reported a first degree relative with MDS, leukemia, lymphoma or other hematologic condition (multiple myeloma [n=4], Waldenstrom’s macroglobulinemia [n=1] and idiopathic thrombocytopenic purpura [n=1]). Treatment related MDS cases were excluded leaving 330 MDS patients for analysis. Unconditional logistic regression was used to calculate crude odds ratios (ORs) and 95% confidence intervals (CI) overall and by sex. Results A total of 61/330 (18.5%) cases reported a family history of a hematologic condition. The mean age at diagnosis was 71.3 years in those with a family history compared to 72.2 years in those without a family history (p=0.53). There was no difference in the sex distribution between the two groups. Though not statistically significant, the odds of having abnormal cytogenetics or an IPSS-R of High/Very High was lower for those having a positive family history (OR 0.57 [CI 0.25-1.33, p=0.19 and 0.67 [CI 0.24-1.84, p=0.29], respectively). The odds of survival at one year after diagnosis was significantly higher in those with a family history (OR 2.79 [CI 1.04-7.51, p=0.04]) compared to those without (Table). Further stratification by sex revealed that this association was strongest for males (OR=4.23, [CI 0.94-19.0, p=0.06] compared to females (OR=1.84 [CI=0.47-7.19, p=0.38]). Discussion In this population based study of adults with MDS, the prevalence of MDS cases having a positive family history was higher than previous reports. Additionally, cases reporting a family history of hematologic malignancies and disorders appear to experience lower risk disease and have significantly improved overall survival, especially males. It is possible that patients with a family history of hematologic conditions are diagnosed earlier in the course of their disease secondary to increased awareness about blood disorders and/or more active screening within the family. Our analysis is limited by relatively small numbers, but enrollment is ongoing so subsequent analyses with larger numbers of subjects may be more revealing. Additionally, a prospective study to examine these families further, including detailed medical histories and collection of biospecimens (saliva, blood, skin) for genetic analyses is underway in order to identify potential mechanisms and mutations involved in the development of MDS and progression to AML. Disclosures: No relevant conflicts of interest to declare.

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Immune-Related and Inflammatory Conditions Likely Play a Role in the Development of Lymphoplasmacytic Lymphoma/Waldenström’s Macroglobulinemia

Blood ◽

10.1182/blood.v112.11.3758.3758 ◽

2008 ◽

Vol 112 (11) ◽

pp. 3758-3758

Author(s):

Sigurdur Y Kristinsson ◽

Magnus Bjorkholm ◽

Jill Koshiol ◽

Lynn R. Goldin ◽

Mary L. McMaster ◽

...

Keyword(s):

Infectious Diseases ◽

Large Population ◽

Population Based ◽

Birth Date ◽

Prior History ◽

Hospital Inpatient ◽

Lymphoplasmacytic Lymphoma ◽

Inflammatory Conditions ◽

Increased Risk ◽

History Of

Abstract Introduction: Certain autoimmune and infectious conditions are associated with increased risks of subtypes of non-Hodgkin lymphomas (NHL). A few prior studies suggest that chronic immune stimulation may particularly elevate risk for the NHL subtype lymphoplasmacytic lymphoma (LPL)/Waldenström’s macroglobulinemia (WM). To improve our understanding on the role of immune-related and inflammatory conditions in LPL/WM pathogenesis, we conducted a large population-based study including close to 2,500 LPL/WM patients diagnosed in Sweden and almost 10,000 matched controls. Methods: Using both the central Cancer registry and local hospital-based registries, we identified all LPL/WM patients diagnosed in Swedish hospitals 1958–2005. From the Swedish Population Registry we identified four matched controls per LPL/WM patient. Through data linkage with the central Inpatient registry, we gathered information on hospital inpatient discharges that listed autoimmune-, infectious-, and other inflammatory/allergic diseases present at least 1 year prior to LPL/WM. Using Poisson regression, we calculated rate ratios (RR) and 95% confidence intervals (CI) adjusted for categorical year of birth, date of diagnosis, gender, and county. Results: A total of 2,470 LPL/WM patients (647 LPL and 1,823 WM), and 9,698 population-based matched controls were included in the study. We found an increased risk of developing LPL/WM among individuals with a prior history of systemic sclerosis (RR=4.7; 1.4–15.3), Sjögren’s syndrome (RR=12.1; 3.3–45.0), autoimmune hemolytic anemia (AIHA) (RR=24.2; 5.4–108.2), polymyalgia rheumatica (RR=2.9; 1.6–5.2), and temporalis arteritis (RR=8.3; 2.1–33.1). We also found excess risk of LPL/WM among persons with a history of pneumonia (RR=1.4; 1.1–1.7), septicaemia (RR=2.4; 1.2–4.3), pyelonephritis (RR=1.7; 1.1–2.5), sinusitis (RR=2.7; 1.4–4.9), herpes zoster (RR=3.4; 2.0–5.6), and influenza (RR=2.9; 1.7–5.0). Importantly, when we assessed the associations by latency (time between immune-related or inflammatory conditions and LPL/WM), for most autoimmune- and infectious diseases the excess LPL/WM risk remained significant at >5 years latency. We found no significant increased risk for LPL/WM among individuals with prior chronic inflammatory or allergic conditions. Conclusions: In the largest investigation of risk factors for LPL/WM to date, we found a personal history of certain autoimmune and infectious diseases to be associated with excess LPL/WM risk. Immune-related conditions might act as potential LPL/WM triggers or they could represent premalignant immune disruptions preceding LPL/WM. Our results provide novel insights into the as yet unclear pathogenesis of LPL/WM.

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Impact Of History Of Autoimmune Disease On Survival In Multiple Myeloma and Monoclonal Gammopathy Of Undetermined Significance: A Population-Based Study

Blood ◽

10.1182/blood.v122.21.1898.1898 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1898-1898

Author(s):

Ebba K Lindqvist ◽

Ingemar Turesson ◽

Ola Landgren ◽

Sigrún H Lund ◽

Lynn Goldin ◽

...

Keyword(s):

Monoclonal Gammopathy ◽

Protein Concentration ◽

Population Based ◽

Personal History ◽

M Protein ◽

Prior History ◽

Population Based Study ◽

Increased Risk ◽

Impact On Survival ◽

History Of

Abstract Background Multiple myeloma (MM) and its precursor state monoclonal gammopathy of undetermined significance (MGUS) are two plasma cell dyscrasias whose etiology is largely unknown. Autoimmune disorders (AI) include a variety of conditions, and a history of AI has been found to increase the risk of several malignancies. A personal history of AI is associated with a significantly increased risk of MGUS and to some extent MM. History of AI is a predictor of poor survival in the general population. Aims The aim of the study was to determine whether a personal history of AI has an impact on survival in MM and MGUS. Methods Using national Swedish registries we identified 2,719 patients with MM, diagnosed between January 1, 2000, and December 31, 2006, and 4,276 patients with MGUS, diagnosed between January 1, 1988, and December 31, 2006, as well as 28,063 matched control subjects. Through the Swedish Inpatient Registry and Cause of Death Registry, we obtained information on previous AI and on survival, respectively, in patients and controls. We calculated hazard ratios (HR) and 95% confidence intervals (CI). We used the Kaplan-Meier method with log-rank test and Cox proportional hazards model to compare outcome among patients and controls with and without AI. We performed sub-group analyses on seven specific AI conditions; rheumatoid arthritis, pernicious anemia, chronic rheumatic heart disease, ulcerative colitis, polymyalgia rheumatica, giant cell arteritis, and psoriasis. We also performed analyses by M-protein concentration and M-protein isotype (MGUS only). Results A history of AI was found in 232 MM patients (9%) and in 822 MM controls (8%). Compared to controls with no history of AI, male and female controls with a history of AI had a significantly 2.1-fold increased (95% CI 1.7-2.4, and 95% CI 1.7-2.5, respectively) risk of dying (Figure 1). In patients with MM and a prior history of AI, compared to MM patients with no history of AI, the risk of dying was significantly increased in females (HR=1.5, 95% CI 1.2-2.0) and in males (HR=1.3, 95% CI 1.0-1.7). The increased risk of dying after a prior AI was greater in MM patients than in controls for the specific AI conditions rheumatoid arthritis (HR=1.8, 95% CI 1.2-2.5 for controls, HR=1.9, 95% CI 1.3-2.9 for MM patients) and giant cell arteritis (HR=1.9, 95% CI 1.1-3.5 for controls, HR=4.1, 95% CI 1.3-12.7 for MM patients). For the other specific conditions analyzed, the increased risk of dying after a prior AI was smaller in MM patients than in controls. A history of AI was found in 570 MGUS patients (13%) and in 1,312 MGUS controls (8%). Compared to controls with no history of AI, male and female controls with a history of AI had a 1.8-fold (95% CI 1.7-2.1) and a 2.4-fold (95% CI 2.2-2.7) increased risk of dying, respectively (Figure 2). In patients with MGUS and a prior history of AI, compared to MGUS patients with no history of AI, the risk of dying was significantly increased in males (HR=1.3, 95% CI 1.1-1.6) and in females (HR=1.9, 95% CI 1.6-2.3). The increased risk of dying after a prior AI was greater in MGUS patients than in controls for the specific AI condition ulcerative colitis (HR= 1.2, 95% CI 0.6-2.5 for controls, HR=2.6, 95% CI 1.4-5.1 for MGUS patients). For the other specific conditions analyzed, the increased risk of dying after a prior AI was smaller in MGUS patients than in controls. In patients with MGUS, the effect of a history of AI on survival was not statistically different by isotype (IgA, IgG, or IgM), or by M-protein concentration (above/below 2.0 g/dl) at MGUS diagnosis. Conclusions In this large, population-based study aimed at evaluating the influence of a history of AI on survival in MM and in MGUS, we found AI to be a risk factor for survival in both conditions. However, a prior AI was a stronger predictor of survival in individuals without MM or MGUS. For certain AI conditions a history of AI had a greater impact on survival in MM or MGUS patients than in the general population. More attention should be paid to comorbidity as a prognostic factor in MM, and to the need for tailoring therapy according to comorbidity. Disclosures: No relevant conflicts of interest to declare.

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Family history of diabetes identifies a group at increased risk for the metabolic consequences of obesity and physical inactivity in EPIC-Norfolk: a population-based study

International Journal of Obesity ◽

10.1038/sj.ijo.0801383 ◽

2000 ◽

Vol 24 (10) ◽

pp. 1333-1339 ◽

Cited By ~ 49

Author(s):

LA Sargeant ◽

NJ Wareham ◽

K-T Khaw

Keyword(s):

Family History ◽

Physical Inactivity ◽

Population Based ◽

Population Based Study ◽

Family History Of Diabetes ◽

Increased Risk ◽

History Of ◽

Consequences Of Obesity

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Family history of venous thromboembolism is associated with increased risk for thrombosis in multiple myeloma: a population-based study

Journal of Thrombosis and Haemostasis ◽

10.1111/j.1538-7836.2012.04676.x ◽

2012 ◽

Vol 10 (5) ◽

pp. 962-964 ◽

Cited By ~ 3

Author(s):

S. Y. KRISTINSSON ◽

L. GOLDIN ◽

I. TURESSON ◽

M. HULTCRANTZ ◽

M. BJÖRKHOLM ◽

...

Keyword(s):

Multiple Myeloma ◽

Venous Thromboembolism ◽

Family History ◽

Population Based ◽

Population Based Study ◽

Increased Risk ◽

History Of ◽

Risk For Thrombosis

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Melanoma is associated with an increased risk of bullous pemphigoid: a large population-based longitudinal study

Archives of Dermatological Research ◽

10.1007/s00403-021-02211-4 ◽

2021 ◽

Author(s):

Khalaf Kridin ◽

Jennifer E. Hundt ◽

Ralf J. Ludwig ◽

Kyle T. Amber ◽

Dana Tzur Bitan ◽

...

Keyword(s):

Bullous Pemphigoid ◽

Statistical Significance ◽

Large Population ◽

Underlying Mechanism ◽

Population Based ◽

Control Subjects ◽

Increased Risk ◽

Bidirectional Association ◽

History Of ◽

Incident Cases

AbstractThe association between bullous pemphigoid (BP) and melanoma is yet to be investigated. We aimed to assess assess the bidirectional association between BP and melanoma and to delineate the epidemiological features of patients with both diagnoses. A population-based cohort study was performed comparing BP patients (n = 3924) with age-, sex- and ethnicity-matched control subjects (n = 19,280) with regard to incident cases of melanoma. A case–control design was additionally adopted to estimate the risk of BP in individuals with a preexisting diagnosis of melanoma. The prevalence of preexisting melanoma was higher in patients with BP than in control subjects (1.5% vs. 1.0%, respectively; P = 0.004). A history of melanoma confers a 50% increase in the risk of subsequent BP (OR 1.53; 95% CI 1.14–2.06). This risk was higher among males (OR 1.66; 95% CI 1.09–2.54) and individuals older than 80 years (OR 1.63; 95% CI 1.11–2.38), and persisted after adjustment for multiple putative confounders including PD-1/PDL-1 antagonists (adjusted OR 1.53; 95% CI 1.14–2.06). Conversely, the risk of melanoma among patients with BP was slightly elevated, but did not reach the level of statistical significance (adjusted HR 1.13; 95% CI 0.73–1.74). Patients with a dual diagnosis of BP and melanoma were older at the onset of BP and had lower body mass index. A history of melanoma is associated with a 50% increase in the incidence of subsequent BP. Physicians managing patients with both conditions should be aware of this association. Further research is warranted to reveal the underlying mechanism of these findings.

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