Differential characteristics of Waldenstrom macroglobulinemia according to patterns of familial aggregation

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
Blood (Impact Factor: 10.45). 03/2010; 115(22):4464-71. DOI: 10.1182/blood-2009-10-247973
Source: PubMed


Familial aggregation of Waldenström macroglobulinemia (WM) and related B-cell disorders (BCDs) suggests a role for genetic factors, but few data address environmental influences. We designed a questionnaire-based study to examine clinical and environmental factors in a cohort of WM families with various patterns of case aggregation. We analyzed data on 103 WM patients and 272 unaffected relatives from 35 multiple-case WM and 46 mixed WM/BCD kindred and 28 nonfamilial (sporadic) WM patients, using logistic regression models with generalized estimating equations to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for association. In this study population, the WM disease process appeared similar among patients regardless of family history. Familial WM patients were more likely than unaffected relatives to report a history of autoimmune disease (OR, 2.27; 95% CI = 1.21-4.28) and infections (OR, 2.13; 95% CI = 1.25-3.64). Familial WM patients were also more likely to report exposure to farming (OR, 2.70; 95% CI = 1.34-5.42), pesticides (OR, 2.83; 95% CI = 1.56-5.11), wood dust (OR, 2.86; 95% CI = 1.54-5.33), and organic solvents (multiple-case WM OR, 4.21; 95% CI = 1.69-10.51) compared with unaffected family members. These data provide clues to both genetic and environmental factors that may influence development of WM. Well-designed case-control studies are needed to confirm these findings.

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Available from: Jill Koshiol, Sep 01, 2015
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    • "Family members of patients with MGUS or MM have a two-three-fold higher risk of developing MGUS and multiple myeloma [19]–[22]. CLL and WM include both sporadic and familial forms of the disease [23]–[26]. Inherited polymorphisms are associated with both CLL and WM [15]; [25]; [27]–[31], and a strongly recurrent somatic mutation with WM [32]. The odds ratios found here for CLL and WM were considerably more pronounced than those found for MM which appears to have less familial influence. "
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    • "Studies of familial aggregation have long been used for generating hypotheses regarding shared genetic and environmental factors [5] [6]. Previous studies suggest that genetic and environmental risk factors for B-cell disorders may also be risk factors for WM [7] [8] [9], but additional hypothesis sources are needed. We thus examined potential associations of WM with "
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