Multiple myeloma (MM) is the second most common blood malignancy. Epidemiological family studies going back to the 1920s have provided evidence for familial aggregation, suggesting a subset of cases have an inherited genetic background. Recently, studies aimed at explaining this phenomenon have begun to provide direct evidence for genetic predisposition to MM. Genome-wide association studies have identified common risk alleles at 24 independent loci. Sequencing studies of familial cases and kindreds have begun to identify promising candidate genes where variants with strong effects on MM risk might reside. Finally, functional studies are starting to give insight into how identified risk alleles promote the development of MM. Here, we review recent findings in MM predisposition field, and highlight open questions and future directions.

Broad Institute 415 Main Street Cambridge MA 02142 USA

Department of Cancer Epidemiology German Cancer Research Center Im Neuenheimer Feld Heidelberg Germany

Division of Genetics and Epidemiology The Institute of Cancer Research 15 Cotswold Road Sutton Surrey SM2 5NG UK

Faculty of Medicine and Biomedical Center Charles University Prague 30605 Pilsen Czech Republic

Hematology and Transfusion Medicine Department of Laboratory Medicine BMC B13 221 84 Lund Sweden

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Deciphering the genetics and mechanisms of predisposition to multiple myeloma

Identification of novel genetic loci for risk of multiple myeloma by functional annotation

Investigation of Rare Non-Coding Variants in Familial Multiple Myeloma

Does a Multiple Myeloma Polygenic Risk Score Predict Overall Survival of Patients with Myeloma?

Functional dissection of inherited non-coding variation influencing multiple myeloma risk

Epidemiology, genetics and treatment of multiple myeloma and precursor diseases

Prevalence of the GFI1-36N SNP in Multiple Myeloma Patients and Its Impact on the Prognosis

Characterization of rare germline variants in familial multiple myeloma