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Over one‐third of African‐American MGUS and multiple myeloma patients are carriers of hyperphosphorylated paratarg‐7, an autosomal dominantly inherited risk factor for MGUS/MM
Author(s) -
Zwick Carsten,
Held Gerhard,
Auth Michaela,
BernalMizrachi Leon,
Roback John D.,
Sunay Susan,
Iida Shinsuke,
Kuroda Yoshiaki,
Sakai Akira,
Ziepert Marita,
Ueda Ryuzo,
Pfreundschuh Michael,
Preuss KlausDieter
Publication year - 2014
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.28731
Subject(s) - paraproteins , monoclonal gammopathy of undetermined significance , multiple myeloma , risk factor , medicine , incidence (geometry) , odds ratio , population , immunology , antibody , monoclonal , monoclonal antibody , physics , environmental health , optics
As hyperphosphorylated paratarg‐7 (pP‐7) carrier state was shown to be the first molecularly defined autosomal dominantly inherited risk factor for monoclonal gammopathy of unknown significance (MGUS) and multiple myeloma (MM) in a European population, the prevalence of pP‐7 carrier state among African‐Americans who have a significantly higher incidence of MGUS/MM is of interest. We therefore determined pP‐7 carrier state and paraproteins with specificity for P‐7 in African‐American, European and Japanese patients with MGUS/MM and healthy controls. By isoelectric focusing and ELISA, a paratarg‐7‐specific paraprotein and the associated pP‐7 carrier state was observed in 30/81 (37.0%) African‐American, 42/252 (16.7%) European and 7/176 (4.0%) Japanese MGUS/MM patients ( p < 0.001). A pP‐7 carrier state was found in 11/100 (11.0%) African‐American, 8/550 (1.5%) European and 1/278 (0.4%) Japanese healthy controls ( p < 0.001), resulting in an odds ratio for MGUS/MM of 4.8 ( p < 0.001) among African‐American, 13.6 among European ( p < 0.001) and 11.5 ( p = 0.023) among Japanese carriers of pP‐7. We conclude that pP‐7 carriers are most prevalent among African‐Americans, but a pP‐7 carrier state is the strongest molecularly defined single risk factor for MGUS/MM known to date in all three ethnic groups. The high prevalence of pP‐7 carriers among African‐American patients emphasizes a predominant role of this genetic factor in the pathogenesis of these diseases. The large number of pP7 African‐American patients and controls should facilitate the identification of the SNP or mutation underlying the pP‐7 carrier state.