title: Risk of plasma cell and lymphoproliferative disorders among 14621 first-degree relatives of 4458 patients with monoclonal gammopathy of undetermined significance in Sweden.
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.
authors.affiliation: Division of Cancer Epidemiology and Genetics, and Center for Cancer Research, Medical Oncology Branch, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA. landgreo@mail.nih.gov
authors.forename: Ola
authors.initials: O
authors.lastname: Landgren
authors.forename: Sigurdur Y
authors.initials: SY
authors.lastname: Kristinsson
authors.forename: Lynn R
authors.initials: LR
authors.lastname: Goldin
authors.forename: Neil E
authors.initials: NE
authors.lastname: Caporaso
authors.forename: Cecilie
authors.initials: C
authors.lastname: Blimark
authors.forename: Ulf-Henrik
authors.initials: UH
authors.lastname: Mellqvist
authors.forename: Anders
authors.initials: A
authors.lastname: Wahlin
authors.forename: Magnus
authors.initials: M
authors.lastname: Bjorkholm
authors.forename: Ingemar
authors.initials: I
authors.lastname: Turesson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005190:Family; D005260:Female; D006801:Humans; D008232:Lymphoproliferative Disorders / Q000453:epidemiology / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D054219:Neoplasms, Plasma Cell / Q000453:epidemiology / Q000209:etiology*; D010265:Paraproteinemias / Q000453:epidemiology; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology