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Blood, 15 October 2008, Vol. 112, No. 8, pp. 3052-3056.
Prepublished online as a Blood First Edition Paper on August 13, 2008; DOI 10.1182/blood-2008-06-162768.
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Submitted June 11, 2008
Accepted August 7, 2008
Risk of lymphoproliferative disorders among first-degree relatives of lymphoplasmacytic lymphoma/Waldenstrom's macroglobulinemia patients: A population-based study in Sweden
Sigurdur Y Kristinsson*, Magnus Bjorkholm, Lynn R. Goldin, Mary L McMaster, Ingemar Turesson, and Ola Landgren
Hematology Center, Internal Medicine Unit, Karolinska University Hospital, Stockholm
NIH, National Cancer Institute, Bethesda
Hematology Section, Malmo University Hospital, Malmo, Sweden
* Corresponding author; email: sigurdur.kristinsson{at}karolinska.se.
A role for genetic factors in the etiology of lymphoplasmacytic lymphoma/Waldenstrom's macroglobulinemia (LPL/WM) is implicated based on prior findings from multiply affected families and small case-control and cohort studies. We identified 2,144 LPL/WM patients (1,539 WM [72%] and 605 LPL [28%]) diagnosed in Sweden, 8,279 population-based matched controls, and linkable first-degree relatives of patients (n=6,177) 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 a 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 (above/below 70 years), and sex of the first-degree relative, we did not observe the risk-estimates to be significantly different compared to 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.
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