Blood Advances (Apr 2017)
Direct evidence for a polygenic etiology in familial multiple myeloma
- Britt-Marie Halvarsson,
- Anna-Karin Wihlborg,
- Mina Ali,
- Konstantinos Lemonakis,
- Ellinor Johnsson,
- Abhishek Niroula,
- Carrie Cibulskis,
- Niels Weinhold,
- Asta Försti,
- Evren Alici,
- Christian Langer,
- Michael Pfreundschuh,
- Hartmut Goldschmidt,
- Ulf-Henrik Mellqvist,
- Ingemar Turesson,
- Anders Waage,
- Kari Hemminki,
- Todd Golub,
- Hareth Nahi,
- Urban Gullberg,
- Markus Hansson,
- Björn Nilsson
Affiliations
- Britt-Marie Halvarsson
- Hematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden;
- Anna-Karin Wihlborg
- Hematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden;
- Mina Ali
- Hematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden;
- Konstantinos Lemonakis
- Hematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden;; Hematology Clinic, Skåne University Hospital, Lund, Sweden;
- Ellinor Johnsson
- Hematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden;
- Abhishek Niroula
- Hematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden;
- Carrie Cibulskis
- Broad Institute, Cambridge, MA;
- Niels Weinhold
- Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany;
- Asta Försti
- German Cancer Research Center, Heidelberg, Germany;; Center for Primary Health Care Research, Lund University, Malmö, Sweden;
- Evren Alici
- Center for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden;
- Christian Langer
- Department of Internal Medicine III, University of Ulm, Ulm, Germany;
- Michael Pfreundschuh
- José Carreras Center for Immuno and Gene Therapy, Department of Internal Medicine I, Saarland University Medical School, Homburg (Saar), Germany;
- Hartmut Goldschmidt
- Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany;; National Center for Tumor Diseases, Heidelberg, Germany;
- Ulf-Henrik Mellqvist
- Section of Hematology, Sahlgrenska University Hospital, Gothenburg, Sweden
- Ingemar Turesson
- Hematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden;
- Anders Waage
- Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
- Kari Hemminki
- German Cancer Research Center, Heidelberg, Germany;; Center for Primary Health Care Research, Lund University, Malmö, Sweden;
- Todd Golub
- Broad Institute, Cambridge, MA;
- Hareth Nahi
- Center for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden;
- Urban Gullberg
- Hematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden;
- Markus Hansson
- Hematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden;; Hematology Clinic, Skåne University Hospital, Lund, Sweden;
- Björn Nilsson
- Hematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden;; Broad Institute, Cambridge, MA;; Björn Nilsson, Hematology and Transfusion Medicine, Department of Laboratory Medicine, BMC B13, 221 84 Lund, Sweden;
- Journal volume & issue
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Vol. 1,
no. 10
pp. 619 – 623
Abstract
Abstract: Although common risk alleles for multiple myeloma (MM) were recently identified, their contribution to familial MM is unknown. Analyzing 38 familial cases identified primarily by linking Swedish nationwide registries, we demonstrate an enrichment of common MM risk alleles in familial compared with 1530 sporadic cases (P = 4.8 × 10−2 and 6.0 × 10−2, respectively, for 2 different polygenic risk scores) and 10 171 population-based controls (P = 1.5 × 10−4 and 1.3 × 10−4, respectively). Using mixture modeling, we estimate that about one-third of familial cases result from such enrichments. Our results provide the first direct evidence for a polygenic etiology in a familial hematologic malignancy.
