Biological determinants of health disparities in multiple myeloma

Cheryl Jacobs Smith, Stefan Ambs, Ola Landgren, Cheryl Jacobs Smith, Stefan Ambs, Ola Landgren

Abstract

Multiple myeloma is a rare plasma cell cancer, and incidence rates among patients of African descent are about twice those among patients of European descent. Rates of multiple myeloma vary among different populations, but the reasons for the racial disparities in multiple myeloma are largely unknown. Epidemiology has identified risk factors for multiple myeloma including race, advanced age, gender, family history, and exposure to different genetic toxins including radiation. Race and ancestry play a large role in predicting the risk for multiple myeloma, yet there exists a paucity of literature that explores the molecular contribution of race and ancestry to disease. In this review, we describe the relevant literature that describes the observed racial differences according to distinct tumor immunobiological and ancestral differences in populations.

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1. Prevalence of monoclonal gammopathy of…
Fig. 1. Prevalence of monoclonal gammopathy of undetermined significance (MGUS) in the among residents of Olmsted County, Minnesota compared to persons from the National Health and Nutritional Examination Survey (NHANES).
Data has been re-plotted from original publications. Olmsted County, MN study (n = 21 462 persons). See reference for Olmsted County, MN prevalence percentages. NHANES study (n = 12 482 persons; n = 2331 non-Hispanic blacks [black or African American], n = 2475 Mexican Amersicans, n = 7051 non-Hispanic whites [white], and n = 625 “others”). See ref. for NHANES prevalence percentages. Age-adjusted prevalence rates are comparable between studies as the prevalence rates have been similarly standardized to the 2000 US population. Data represents patients over 50 years of age and includes the sexes men and women. AA, African American; WH, Whites. *NHANES age-adjusted prevalence rate contains information from Mexican Americans, whites, and African Americans. However, rates are similar among Mexican Americans and whites. MGUS estimation from the NHANES study likely reflects the true estimate as it is the most representative cohort of the United States population
Fig. 2. The Yin and Yang of…
Fig. 2. The Yin and Yang of mortality and survival in multiple myeloma.
a, b, c Age-adjusted rates of multiple myeloma incidence (a), mortality (b), and 5-year survival percentae (c) in all races (red, diamond), blacks (green, circle), and whites (blue, square) from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute (NCI) between 1975 and 2014. Despite the 2–3 times higher incidence and mortality observed among blacks with multiple myeloma, the 5-year survival for blacks is equal to superior to whites given the year

References

    1. Benjamin M, Reddy S, Brawley OW. Myeloma and race: a review of the literature. Cancer Metastas. Rev. 2003;22:87–93. doi: 10.1023/A:1022268103136.
    1. Howlader N. N. A., et al. SEER Cancer Statistics Review, 1975–2014. 2017; based on November 2016 SEER data submission.
    1. Landgren O, et al. Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study. Blood. 2009;113:5412–5417. doi: 10.1182/blood-2008-12-194241.
    1. Weiss BM, Abadie J, Verma P, Howard RS, Kuehl WM. A monoclonal gammopathy precedes multiple myeloma in most patients. Blood. 2009;113:5418–5422. doi: 10.1182/blood-2008-12-195008.
    1. Weiss BM, et al. Patterns of monoclonal immunoglobulins and serum free light chains are significantly different in black compared to white monoclonal gammopathy of undetermined significance (MGUS) patients. Am. J. Hematol. 2011;86:475–478. doi: 10.1002/ajh.22025.
    1. Kyle RA, Rajkumar SV. Epidemiology of the plasma-cell disorders. Best Pract. Res. Clin. Haematol. 2007;20:637–664. doi: 10.1016/j.beha.2007.08.001.
    1. Alexander DD, et al. Multiple myeloma: a review of the epidemiologic literature. Int. J. Cancer. 2007;120(Suppl 12):40–61. doi: 10.1002/ijc.22718.
    1. McFarlane H. Multiple myeloma in Jamaica: a study of 40 cases with special reference to the incidence and laboratory diagnosis. J. Clin. Pathol. 1966;19:268–271. doi: 10.1136/jcp.19.3.268.
    1. Talerman A. Clinico-pathological study of multiple myeloma in Jamaica. Br. J. Cancer. 1969;23:285–293. doi: 10.1038/bjc.1969.38.
    1. McFarlane H, Talerman A, Steinberg AG. Immunoglobulins in Jamaicans and Nigerians with immunogenetic typing of myeloma and lymphoma in Jamaicans. J. Clin. Pathol. 1970;23:124–126. doi: 10.1136/jcp.23.2.124.
    1. Brown LM, Gridley G, Check D, Landgren O. Risk of multiple myeloma and monoclonal gammopathy of undetermined significance among white and black male United States veterans with prior autoimmune, infectious, inflammatory, and allergic disorders. Blood. 2008;111:3388–3394. doi: 10.1182/blood-2007-10-121285.
    1. Landgren O, Weiss BM. Patterns of monoclonal gammopathy of undetermined significance and multiple myeloma in various ethnic/racial groups: support for genetic factors in pathogenesis. Leukemia. 2009;23:1691–1697. doi: 10.1038/leu.2009.134.
    1. Greenberg AJ, Vachon CM, Rajkumar SV. Disparities in the prevalence, pathogenesis and progression of monoclonal gammopathy of undetermined significance and multiple myeloma between blacks and whites. Leukemia. 2012;26:609–614. doi: 10.1038/leu.2011.368.
    1. Baker A, et al. Uncovering the biology of multiple myeloma among African Americans: a comprehensive genomics approach. Blood. 2013;121:3147–3152. doi: 10.1182/blood-2012-07-443606.
    1. Landgren O, et al. Prevalence of monoclonal gammopathy of undetermined significance among men in Ghana. Mayo Clin. Proc. 2007;82:1468–1473. doi: 10.1016/S0025-6196(11)61089-6.
    1. Landgren O, et al. Racial disparities in the prevalence of monoclonal gammopathies: a population-based study of 12,482 persons from the National Health and Nutritional Examination Survey. Leukemia. 2014;28:1537–1542. doi: 10.1038/leu.2014.34.
    1. Soderberg KC, Hagmar L, Schwartzbaum J, Feychting M. Allergic conditions and risk of hematological malignancies in adults: a cohort study. BMC Public Health. 2004;4:51. doi: 10.1186/1471-2458-4-51.
    1. Kristinsson SY, et al. Genetic and immune-related factors in the pathogenesis of lymphoproliferative and plasma cell malignancies. Haematologica. 2009;94:1581–1589. doi: 10.3324/haematol.2009.008979.
    1. Dosani T, Carlsten M, Maric I, Landgren O. The cellular immune system in myelomagenesis: NK cells and T cells in the development of MM and their uses in immunotherapies. Blood Cancer J. 2015;5:e321. doi: 10.1038/bcj.2015.49.
    1. Rajkumar SV, Kyle RA, Buadi FK. Advances in the diagnosis, classification, risk stratification, and management of monoclonal gammopathy of undetermined significance: implications for recategorizing disease entities in the presence of evolving scientific evidence. Mayo Clin. Proc. 2010;85:945–948. doi: 10.4065/mcp.2010.0520.
    1. Zingone A, Kuehl WM. Pathogenesis of monoclonal gammopathy of undetermined significance and progression to multiple myeloma. Semin. Hematol. 2011;48:4–12. doi: 10.1053/j.seminhematol.2010.11.003.
    1. Cohen HJ, Crawford J, Rao MK, Pieper CF, Currie MS. Racial differences in the prevalence of monoclonal gammopathy in a community-based sample of the elderly. Am. J. Med. 1998;104:439–444. doi: 10.1016/S0002-9343(98)00080-1.
    1. Landgren O, et al. Risk of monoclonal gammopathy of undetermined significance (MGUS) and subsequent multiple myeloma among African American and white veterans in the United States. Blood. 2006;107:904–906. doi: 10.1182/blood-2005-08-3449.
    1. Landgren O, et al. Prevalence of myeloma precursor state monoclonal gammopathy of undetermined significance in 12372 individuals 10-49 years old: a population-based study from the National Health and Nutrition Examination Survey. Blood Cancer J. 2017;7:e618. doi: 10.1038/bcj.2017.97.
    1. Kyle RA, et al. Prevalence of monoclonal gammopathy of undetermined significance. N. Engl. J. Med. 2006;354:1362–1369. doi: 10.1056/NEJMoa054494.
    1. Jain M, Ascensao J, Schechter GP. Familial myeloma and monoclonal gammopathy: a report of eight African American families. Am. J. Hematol. 2009;84:34–38. doi: 10.1002/ajh.21325.
    1. Gragert L, et al. Fine-mapping of HLA associations with chronic lymphocytic leukemia in US populations. Blood. 2014;124:2657–2665. doi: 10.1182/blood-2014-02-558767.
    1. Beksac M, et al. HLA polymorphism and risk of multiple myeloma. Leukemia. 2016;30:2260–2264. doi: 10.1038/leu.2016.199.
    1. Prokunina-Olsson L, et al. A variant upstream of IFNL3 (IL28B) creating a new interferon gene IFNL4 is associated with impaired clearance of hepatitis C virus. Nat. Genet. 2013;45:164–171. doi: 10.1038/ng.2521.
    1. Aka PV, et al. Association of the IFNL4-DeltaG allele with impaired spontaneous clearance of hepatitis C virus. J. Infect. Dis. 2014;209:350–354. doi: 10.1093/infdis/jit433.
    1. Pulte D, Redaniel MT, Brenner H, Jansen L, Jeffreys M. Recent improvement in survival of patients with multiple myeloma: variation by ethnicity. Leuk. Lymphoma. 2014;55:1083–1089. doi: 10.3109/10428194.2013.827188.
    1. Waxman AJ, et al. Racial disparities in incidence and outcome in multiple myeloma: a population-based study. Blood. 2010;116:5501–5506. doi: 10.1182/blood-2010-07-298760.
    1. Fast Stats: An interactive tool for access to SEER cancer statistics.
    1. Greenberg AJ, et al. Racial differences in primary cytogenetic abnormalities in multiple myeloma: a multi-center study. Blood Cancer J. 2015;5:e271. doi: 10.1038/bcj.2014.91.
    1. Manojlovic Z, et al. Comprehensive molecular profiling of 718 Multiple Myelomas reveals significant differences in mutation frequencies between African and European descent cases. PLoS Genet. 2017;13:e1007087. doi: 10.1371/journal.pgen.1007087.
    1. Wallace TA, et al. Tumor immunobiological differences in prostate cancer between African-American and European-American men. Cancer Res. 2008;68:927–936. doi: 10.1158/0008-5472.CAN-07-2608.
    1. Powell IJ, et al. Genes associated with prostate cancer are differentially expressed in African American and European American men. Cancer Epidemiol Biomark Prev. 2013;22:891–897. doi: 10.1158/1055-9965.EPI-12-1238.
    1. Rose AE, et al. Copy number and gene expression differences between African American and Caucasian American prostate cancer. J. Transl. Med. 2010;8:70. doi: 10.1186/1479-5876-8-70.
    1. Hardiman G, et al. Systems analysis of the prostate transcriptome in African-American men compared with European-American men. Pharmacogenomics. 2016;17:1129–1143. doi: 10.2217/pgs-2016-0025.
    1. Reis BS, et al. Prostate cancer progression correlates with increased humoral immune response to a human endogenous retrovirus GAG protein. Clin. Cancer Res. 2013;19:6112–6125. doi: 10.1158/1078-0432.CCR-12-3580.
    1. Goering W, Ribarska T, Schulz WA. Selective changes of retroelement expression in human prostate cancer. Carcinogenesis. 2011;32:1484–1492. doi: 10.1093/carcin/bgr181.
    1. Pérot P. et al. Microarray-based identification of individual HERV loci expression: application to biomarker discovery in prostate cancer. J Vis Exp. e50713 (2013). 10.3791/50713
    1. Wallace TA, et al. Elevated HERV-K mRNA expression in PBMC is associated with a prostate cancer diagnosis particularly in older men and smokers. Carcinogenesis. 2014;35:2074–2083. doi: 10.1093/carcin/bgu114.
    1. Macfarlane C, Simmonds P. Allelic variation of HERV-K(HML-2) endogenous retroviral elements in human populations. J. Mol. Evol. 2004;59:642–656. doi: 10.1007/s00239-004-2656-1.
    1. Jha AR, et al. Cross-sectional dating of novel haplotypes of HERV-K 113 and HERV-K 115 indicate these proviruses originated in Africa before Homo sapiens. Mol. Biol. Evol. 2009;26:2617–2626. doi: 10.1093/molbev/msp180.
    1. Smith CJ, et al. Aspirin use reduces the risk of aggressive prostate cancer and disease recurrence in African-American men. Oncology. 2017;26:845–853.
    1. Buadi F, et al. High prevalence of polyclonal hypergamma-globulinemia in adult males in Ghana, Africa. Am. J. Hematol. 2011;86:554–558. doi: 10.1002/ajh.22040.
    1. Idelman G, et al. Functional profiling of uncommon VCAM1 promoter polymorphisms prevalent in African American populations. Hum. Mutat. 2007;28:824–829. doi: 10.1002/humu.20523.

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