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Differences in genomic abnormalities among African individuals with monoclonal gammopathies using calculated ancestry

Baughn, Linda B ; Pearce, Kathryn ; Larson, Dirk ; Polley, Mei-Yin ; Elhaik, Eran LU ; Baird, Michael ; Colby, Colin ; Benson, Joanne ; Li, Zhuo and Asmann, Yan , et al. (2018) In Blood Cancer Journal 8.
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... (More)

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.

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publication status
published
keywords
Adult, African Continental Ancestry Group/genetics, Aged, Aged, 80 and over, Chromosome Aberrations, Chromosome Banding, Disease Progression, Female, Gene Rearrangement, Genes, myc, Genetic Variation, Humans, In Situ Hybridization, Fluorescence, Male, Middle Aged, Odds Ratio, Paraproteinemias/diagnosis
in
Blood Cancer Journal
volume
8
article number
96 (2018)
pages
10 pages
publisher
Nature Publishing Group
external identifiers
  • pmid:30305608
  • scopus:85054626458
ISSN
2044-5385
DOI
10.1038/s41408-018-0132-1
language
English
LU publication?
no
id
2daea72e-bc57-48a3-9a31-c3bd4247c762
date added to LUP
2019-11-10 16:35:58
date last changed
2020-06-03 05:12:54
@article{2daea72e-bc57-48a3-9a31-c3bd4247c762,
  abstract     = {<p>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 (&lt;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.</p>},
  author       = {Baughn, Linda B and Pearce, Kathryn and Larson, Dirk and Polley, Mei-Yin and Elhaik, Eran and Baird, Michael and Colby, Colin and Benson, Joanne and Li, Zhuo and Asmann, Yan and Therneau, Terry and Cerhan, James R and Vachon, Celine M and Stewart, A Keith and Bergsagel, P Leif and Dispenzieri, Angela and Kumar, Shaji and Rajkumar, S Vincent},
  issn         = {2044-5385},
  language     = {eng},
  month        = {10},
  publisher    = {Nature Publishing Group},
  series       = {Blood Cancer Journal},
  title        = {Differences in genomic abnormalities among African individuals with monoclonal gammopathies using calculated ancestry},
  url          = {http://dx.doi.org/10.1038/s41408-018-0132-1},
  doi          = {10.1038/s41408-018-0132-1},
  volume       = {8},
  year         = {2018},
}