The CCND1 870G Risk Allele Is Enriched in African Individuals with Plasma Cell Dyscrasias

• Published in: Blood 2019-11, Vol.134 (Supplement_1), p.4362-4362
• Main Authors: Baughn, Linda B, Li, Zhou, Pearce, Kathryn E., Vachon, Celine M., Polley, Mei-Yin, Keats, Jonathan J, Elhaik, Eran, Baird, Michael L., Therneau, Terry, Cerhan, James R., Bergsagel, P. Leif, Dispenzieri, Angela, Rajkumar, S.Vincent, Asmann, Yan, Kumar, Shaji K.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2019-124979

Purpose: Multiple myeloma (MM) is a plasma cell (PC) malignancy with an increasing incidence in the US. Epidemiological studies demonstrate a 2-3 fold higher incidence of the pre-malignant monoclonal gammopathy of undetermined significance (MGUS) and MM with a ~4-year younger age of onset among African Americans (AA) compared to European Americans (EAs) (Fonseca, Leukemia, 2017). With equal access to care, AAs have better overall survival compared to EAs (Waxman, Blood, 2010). This disparity may be explained by ancestral-associated genetic predisposition of AAs to development of monoclonal gammopathies and to specific acquired, cytogenetically-defined subtypes. Using calculated genetic ancestry data, we have previously identified a higher prevalence of IgH translocations t(11;14), t(14;16) and t(14;20) in individuals with >80% African ancestry (Baughn, BCJ, 2018). Since SNP rs9344 encoding the CCND1 870G>A polymorphism has been reported in association with increased risk of t(11;14) (Weinhold, Nature Genetics, 2013), we investigated whether rs9344 correlates with African ancestry and with t(11;14) in our cohort of patients with plasma cell dyscrasias. Methods: We studied 898 patients with monoclonal gammopathies who had undergone uniform testing to identify MM-specific cytogenetic abnormalities. DNA from bone marrow samples was genotyped on the Precision Medicine Research Array and biogeographical ancestry was assessed using the Geographic Population Structure Origins tool (Elhaik, Nat Commun, 2014). Plasma cell proliferative disorder FISH of immunoglobulin (cIg)-stained positive plasma cells was performed as described (Baughn, BCJ, 2018). Individuals were divided into three ancestral groups: 1. EAs (