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

Blood. 2008 Oct 15;112(8):3052-6. doi: 10.1182/blood-2008-06-162768. Epub 2008 Aug 13.

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.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Family Health
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / epidemiology*
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • Lymphoproliferative Disorders / diagnosis
  • Lymphoproliferative Disorders / epidemiology*
  • Lymphoproliferative Disorders / genetics*
  • Male
  • Middle Aged
  • Registries
  • Sweden
  • Waldenstrom Macroglobulinemia / epidemiology*
  • Waldenstrom Macroglobulinemia / genetics*