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

Abstract

Monoclonal gammopathy of undetermined significance (MGUS) is one of the most common premalignant disorders in Western countries. Recent studies show that almost every multiple myeloma (MM) case is preceded by an MGUS stage. Interestingly, prevalence and incidence patterns for MGUS and MM show striking disparity patterns across ethnic/racial groups, most notably the two-to threefold increase in both these disorders in African Americans compared with Caucasians. In contrast, studies on Asian patients show lower prevalence/ incidence for MGUS/MM compared with Caucasians. Familial aggregation for both MGUS and MM has been observed; the risk for MGUS or MM in family members with these disorders is increased about two-to three fold compared with the general population. Although underlying mechanisms remain unclear, there is evidence of heterogeneity among MGUS patients from different ethnic/racial groups. For example, compared with Caucasians, African-American and African MGUS patients have reportedly lower rates of immunoglobulin M (IgM) MGUS (versus IgG/IgA MGUS) and higher rates of unquantifiable immunoglobulins (Igs). This review focuses on racial disparity and familial aggregation patterns for MGUS and MM and discusses how these observations provide novel clues with regard to pathogenesis.

Risk of multiple myeloma is associated with polymorphisms within telomerase genes and telomere length

“…The two polymorphisms in the TERC region are in strong LD (r 2 5 0.82), indicating that the two associations found are not independent and represent the same locus. 4 Odds ratio (95% confidence interval). All analyses were adjusted for age at diagnosis/age at recruitment, gender and country of origin.…”

“…3,4 Several risk loci have been proposed and a few have been identified through genomewide association studies (GWAS). 2,[5][6][7][8][9][10][11] The genetic variability of the telomerase reverse transcriptase (TERT) and the telomerase RNA component (TERC) gene regions could play a role in MM etiology for two reasons: first the two genes are responsible for crucial cellular processes, namely telomere homeostasis, second their polymorphic variants have been found to be associated with multiple cancer types and other human phenotypes.…”

Compression of the Seventh Cervical Vertebra Following C6-7 and C7-T1 Discectomy, PEEK Cage Implantation in these Intervertebral Spaces, and Management of this Complication in a Patient with Multiple Myeloma

“…Furthermore, MM is a disease that affects the elderly, with a peak incidence between 65 and 70 years [4,17], and osteoporosis frequently occurs in postmenopausal women [18]. Finally, we have sufficient evidence/data to explain the presented patient's compression fractures: her age (68 years), pre-existing osteoporosis associated with her age, corticosteroid treatment for MM, and, lastly and most importantly, the effect and infiltration of plasma cells on bone tissues [2,[5][6][7].…”

“…Bone pain, kidney failure, hypercalcemia, anemia, and recurrent infection are common manifestations of MM [1][2][3]. The incidence of MM is 3-4/100,000 [4], the male/female ratio is 3:2, and most patients are aged >40 years [5,6]. Diffuse osteoporosis or discrete osteolytic lesions develop, usually in the pelvis, spine, ribs, and skull.…”

Spotlight review series on multiple myeloma

“…The rapid pace of changes in the myeloma field has resulted in the need for revising existing diagnostic, prognostic and response criteria, as well as treatment recommendations. 23,30 In this regard, the spotlight series [31][32][33][34][35][36][37][38][39][40][41][42][43][44] includes consensus statements on controversial and evolving areas such as molecular classification and new laboratory tests. We are confident that the myeloma spotlight series will be a resource for all investigators in the field, as well as clinical practitioners treating myeloma, laboratory scientists in related fields and other hematologists.…”