All ETDs from UAB

Advisory Committee Chair

Elizabeth E Brown

Advisory Committee Members

Luciano J Costa

William M Geisler

Ralph D Sanderson

Hemant K Tiwari

Sooryanarayana Varambally

Document Type

Dissertation

Date of Award

2018

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

Multiple myeloma (MM) is a hematologic malignancy in which clonal plasma cells accumulate in the bone marrow, leading to the formation of lytic bone lesions, hypercalcemia, anemia, renal insufficiency, and immunosuppression. It develops from a pre-malignant condition known as monoclonal gammopathy of undetermined significance (MGUS), which is prevalent in up to 3% of White populations over the age of 50 years, and twice that in Black populations. Although much progress has been made toward understanding the large scale genomic aberrations that facilitate the formation of MGUS clones and the various copy-number variations and mutations that trigger the development of MM, the underlying events that drive these changes is still unknown. In addition, improved MM biomarkers are of great interest, as they may provide improved strategies for diagnosis and risk stratification. In this dissertation, we use data from the Molecular And Genetic Epidemiology (iMAGE) study of multiple myeloma to explore various immune-stimulating allergic, autoimmune, and infectious conditions as potential MGUS and MM risk factors in Black and White cases and controls. We found a consistent decrease in MM risk associated with a past history of allergies, and besides chicken pox, observed limited evidence to support most immune-stimulating conditions as risk factors of MM. We did not detect significant differences in effect between Blacks and Whites. In addition, we performed a systematic review of the literature used to assess circulating microRNAs (miRNA) as potential MM biomarkers. We found that of the 56 individual circulating miRNAs evaluated for differential expression in MM cases, only 14 miRNAs were tested in more than one study, and these results were mostly inconsistent across studies.

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