Familial myeloma and monoclonal gammopathy: A report of eight African American families

Abstract

Previous descriptions of familial myeloma have been mainly of Caucasian families. We report here eight African American families with familial multiple myeloma and monoclonal gammopathy identified over a 30 year period. Six patients with multiple myeloma (MM) and two with monoclonal gammopathy of unknown significance (MGUS) reported a family history of MM or had family members with MGUS found on screening. A pedigree compiled for each family included a history of other cancers. In the eight families, 21 of 58 first degree relatives had a plasma cell dyscrasia including 12 MM, eight MGUS, and one amyloidosis patient(s). The age of the MM patients ranged from 50 to 78 years (median 61 years). Four families had two members with MM, including one mother-son and three sibling pairs. Two MM families each had two additional first degree relatives with MGUS, with three generations involved in one family. Anticipation was suggested in two families with parent-child pairs with monoclonal gammopathy. The eight pedigrees had 66 members, 21 of whom had a diagnosis of cancer, including non-Hodgkin lymphoma and Hodgkin disease, or a clonal myeloproliferative disorder other than MM. Although the mode of genetic transmission and anticipation cannot be confirmed due to the small sample size, the increased number of MM and MGUS family members suggests underlying genetic susceptibility factors for plasma cell dyscrasias and possibly for other cancers in these families. Am. J. Hematol. 84:34-38, 2009. V V C 2008 Wiley-Liss, Inc. IntroductionMultiple myeloma (MM) is a progressive disease of malignant plasma cells causing 20% of the deaths due to hematologic malignancies [1]. A more common clonal plasma cell disorder is monoclonal gammopathy of unknown significance (MGUS) which occurs in 1-2% of the population over the age of 50 years and is associated with progression to malignant plasma cell disorders at a rate of 1% per year [2]. The incidence rate of MM is twice as high for African Americans (AAs) (11.3 per 100,000) when compared with Whites (5.1 per 100,000) [3]. Similarly, it has been shown that MGUS is found more frequently in AAs than in White individuals [4][5][6].Several studies have investigated possible reasons for the race-related differences in MM. Pottern et al. [7] showed an association between MM and the HLA-Cw2 allele; however, this allele was found in the same frequency in AA and Caucasian controls, suggesting other factors must play a role. Brown et al. [8] found that cigarette smoking and alcohol intake could not account for the disparity in the incidence rates. Other work has suggested that environmental factors such as exposure to pesticides and solvents or genetic factors such as translocations involving Chromosomes 13 and 14 may play a role [9,10].There have been many reports of the familial occurrence of myeloma in the literature, implying a hereditary element or a common environmental factor [11][12][13][14][15][16]. Most of these families have been of Caucasian origin. A recent study [16] investigated 39 MM...

Patterns of monoclonal gammopathy of undetermined significance and multiple myeloma in various ethnic/racial groups: support for genetic factors in pathogenesis

“…Lynch et al 33 described an African-American family with five cases of MM, three case of MGUS and five cases of prostate cancer among 11 first-degree relatives. Jain et al 34 reported on eight African-American families with familial MM and MGUS seen in a 30-year period at a single institution. A total of 21 of 58 first-degree relatives had a plasma cell dyscrasia including 12 MM, eight MGUS and one amyloidosis.…”

“…Additional malignancies were found 21 other family members, most commonly leukemia, lymphoma and myeloproliferative disorders (n ¼ 5), breast cancer (n ¼ 4), prostate cancer (n ¼ 3) and colon cancer (n ¼ 3). 34 …”

Familial monoclonal gammopathy of undetermined significance and multiple myeloma: epidemiology, risk factors, and biological characteristics

“…Another investigation focused on examining the pedigrees of 6 African American patients with MM and 2 with MGUS. 12 Of the 58 first-degree blood relatives, 21 were found to have a plasma cell disorder (12 MM, 8 MGUS, 1 amyloidosis; Table 1). Despite the small sample size in both of these studies and lack of comparison groups, both indicate possible underlying genetic factors that could play a role in susceptibility in African American populations.…”

A Rare Case of Renal Recovery in a Young Patient with Multiple Myeloma

“…MM has been known to be a disease of older adults, where the median age at diagnosis is 66 years. Only 10 percent are younger than 50 years, and a mere 2 percent of patients are younger than 40 years [6, 7]. …”