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Abstract
Multiple myeloma (MM) is two- to three-fold more common in African Americans (AAs) compared to European Americans (EAs). This striking disparity, one of the highest of any cancer, may be due to underlying genetic predisposition between these groups. There are multiple unique cytogenetic subtypes of MM, and it is likely that the disparity is associated with only certain subtypes. Previous efforts to understand this disparity have relied on self-reported race rather than genetic ancestry, which may result in bias. To mitigate these difficulties, we studied 881 patients with monoclonal gammopathies who had undergone uniform testing to identify primary cytogenetic abnormalities. DNA from bone marrow samples was genotyped on the Precision Medicine Research Array and biogeographical ancestry was quantitatively assessed using the Geographic Population Structure Origins tool. The probability of having one of three specific subtypes, namely t(11;14), t(14;16), or t(14;20) was significantly higher in the 120 individuals with highest African ancestry (≥80%) compared with the 235 individuals with lowest African ancestry (<0.1%) (51% vs. 33%, respectively, p value = 0.008). Using quantitatively measured African ancestry, we demonstrate a major proportion of the racial disparity in MM is driven by disparity in the occurrence of the t(11;14), t(14;16), and t(14;20) types of MM.
Highlights
Monoclonal gammopathies, such as multiple myeloma (MM), represent a collection of plasma cell (PC) neoplasms comprised of mostly incurable hematopoietic malignancies with an increasing incidence (~6 cases per 100,000 individuals during 2008–2012) in the United States[1,2]
Higher prevalence of monoclonal gammopathy of undetermined significance (MGUS) and a higher incidence of MM, along with a ~4-year younger age of onset compared to European Americans (EAs)[3]
From the 881 samples, self-reported race was available from 393 individuals and 161 self-reported as African and 185 self-reported as non-Hispanic Caucasian
Summary
Monoclonal gammopathies, such as multiple myeloma (MM), represent a collection of plasma cell (PC) neoplasms comprised of mostly incurable hematopoietic malignancies with an increasing incidence (~6 cases per 100,000 individuals during 2008–2012) in the United States[1,2]. MM is the most common hematologic malignancy in African Americans (AAs). AAs have a 2–3-fold higher prevalence of monoclonal gammopathy of undetermined significance (MGUS) and a higher incidence of MM, along with a ~4-year younger age of onset compared to European Americans (EAs)[3]. The increased incidence of MM among AAs has been attributed to the increased prevalence of MGUS, with a similar risk of MGUS to MM progression between EAs and AAs3. The combined observations that MGUS/MM clusters in families observed by a 2–4-fold increased risk of first-degree relatives of MM5–7, the higher incidence of MGUS among AAs and Western
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