BACKGROUND: Genome-wide association studies (GWAS) of multiple myeloma in populations of European ancestry (EA) identified and confirmed 24 susceptibility loci. For other cancers (e.g., colorectum and melanoma), risk loci have also been associated with patient survival. METHODS: We explored the possible association of all the known risk variants and their polygenic risk score (PRS) with multiple myeloma overall survival (OS) in multiple populations of EA [the International Multiple Myeloma rESEarch (IMMEnSE) consortium, the International Lymphoma Epidemiology consortium, CoMMpass, and the German GWAS] for a total of 3,748 multiple myeloma cases. Cox proportional hazards regression was used to assess the association between each risk SNP with OS under the allelic and codominant models of inheritance. All analyses were adjusted for age, sex, country of origin (for IMMEnSE) or principal components (for the others) and disease stage (ISS). SNP associations were meta-analyzed. RESULTS: SNP associations were meta-analyzed. From the meta-analysis, two multiple myeloma risk SNPs were associated with OS (P < 0.05), specifically POT1-AS1-rs2170352 [HR = 1.37; 95% confidence interval (CI) = 1.09-1.73; P = 0.007] and TNFRSF13B-rs4273077 (HR = 1.19; 95% CI = 1.01-1.41; P = 0.04). The association between the combined 24 SNP MM-PRS and OS, however, was not significant. CONCLUSIONS: Overall, our results did not support an association between the majority of multiple myeloma risk SNPs and OS. IMPACT: This is the first study to investigate the association between multiple myeloma PRS and OS in multiple myeloma.

Biomedical Center Faculty of Medicine Charles University in Pilsen Pilsen Czech Republic

Cancer Epidemiology Division Cancer Council Victoria Melbourne Victoria Australia

CCU Molecular Hematology Oncology German Cancer Research Center Heidelberg Germany

Centre for Epidemiology and Biostatistics School of Population and Global Health The University of Melbourne Melbourne Victoria Australia

Clinical and Experimental Medicine Section of Hematology University of Pisa Pisa Italy

Community Engagement Program Clinical and Translational Science Center University of California Davis Sacramento California

Department of Biochemistry and Molecular Medicine School of Medicine University of California Davis Sacramento California

Department of Biology University of Pisa Pisa Italy

Department of Epidemiology and Biostatistics Arnold School of Public Health University of South Carolina Greenville South Carolina

Department of Haematology and Bone Marrow Transplantation SSM im M Kopernika Torun Poland

Department of Haematology Rigshospitalet Copenhagen University Copenhagen Denmark

Department of Hematology and Internal Medicine Semmelweis University Budapest Hungary

Department of Hematology and Transplantology Medical Univeristy of Gdańsk Gdańsk Poland

Department of Hematology Institute of Medical Sciences College of Medical Sciences University of Rzeszów Rzeszów Poland

Department of Hematology Medical University of Lodz Lodz Poland

Department of Hematology Military Institute of Medicine Warsaw Poland

Department of Hematology Rydygier Hospital Cracow Poland

Department of Hematology Specialist Hospital No 1 in Bytom Bytom Poland

Department of Hematology Transplantation and Internal Disease Medical University of Warsaw Warsaw Poland

Department of Hematology University Hospital Bydgoszcz Bydgoszcz Poland

Department of Hematology University Hospital of Cracow Cracow Poland

Department of Hematooncology and Bone Marrow Transplantation Medical University of Lublin Poland

Department of Internal and Occupational Diseases Medical University Wroclaw Wroclaw Poland

Department of Internal Medicine 5 University of Heidelberg Heidelberg Germany

Department of Lymphoma Myeloma Division of Cancer Medicine The University of Texas MD Anderson Cancer Center Houston Texas

Department of Medicine University of California San Francisco Helen Diller Family Comprehensive Cancer Center San Francisco California

Department of Pathology School of Medicine University of Alabama Birmingham Alabama

Division of Biostatistics German Cancer Research Center Heidelberg Germany

Division of Cancer Epidemiology and Genetics NCI NIH Bethesda Maryland

Division of Cancer Epidemiology German Cancer Research Center Heidelberg Germany

Division of Computational Biology Department of Quantitative Health Sciences Mayo Clinic Rochester Minnesota

Division of Epidemiology Department of Quantitative Sciences Mayo Clinic Rochester Minnesota

Division of Hematology and Huntsman Cancer Institute University of Utah Salt Lake City Utah

Division of Hematology Department of Internal Medicine Mayo Clinic Rochester Minnesota

Division of Hematology Oncology Department of Medicine School of Medicine Department of Pathology School of Medicine Susan and Henry Samueli College of Health Sciences Chao Family Comprehensive Cancer Center University of California at Irvine California

Division of Pediatric Neurooncology German Cancer Research Center Heidelberg Germany

Division of Population Oncology Cancer Control Research BC Cancer Vancouver Bristish Columbia Canada

Genomic Epidemiology Group German Cancer Research Center Heidelberg Germany

Genomic Oncology Area GENYO Centre for Genomics and Oncological Research Pfizer University of Granada Andalusian Regional Government Granada Spain

Hematology Clinic Holycross Cancer Center Kielce Poland

Hematology department Virgen de las Nieves University Hospital Granada Spain

Hopp Children's Cancer Center Heidelberg Germany

Latinos United for Cancer Health Advancement Initiative University of California Davis Comprehensive Cancer Center Sacramento California

Life and Health Sciences Research Institute School of Health Sciences University of Minho Braga Portugal and ICVS 3B's PT Government Associate Laboratory Braga Guimarães Portugal

Molecular Oncology Research Center Barretos Cancer Hospital Barretos Brazil

Plasma Cell Dyscrasias Center Department of Hematology Faculty of Medicine Jagiellonian University Kraków Poland

Precision Medicine School of Clinical Sciences at Monash Health Monash University Clayton Victoria Australia

Program in Epidemiology Public Health Sciences Division Fred Hutchinson Cancer Research Center Seattle Washington

Servicio de Hematología Centro de Actividades Ambulatorias Madrid Spain

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