Format

Send to

Choose Destination
Nat Commun. 2015 Jul 22;6:7539. doi: 10.1038/ncomms8539.

Genome-wide association study identifies variants at 16p13 associated with survival in multiple myeloma patients.

Author information

1
Department of Medicine, Division of General Internal Medicine, Institute for Human Genetics, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.
2
Sutter Medical Center of Santa Rosa, Santa Rosa, California.
3
Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
4
Division of Biomedical Statistics and Informatics. Department of Health Sciences Research, Mayo Clinic, Jacksonville, FL, USA.
5
Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA.
6
Department of Medicine, Division of Hematology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.
7
Department of Epidemiology and Biostatistics, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.
8
Department of Oncology, Transplants and Advanced Technologies, Section of Hematology, Pisa University Hospital, Pisa, Italy.
9
Department of Molecular Pharmacology and Experimental Therapeutics, College of Medicine, Mayo Clinic, Rochester, MN.
10
INSERM UMR 1052 / CNRS 5286, Laboratoire de Cytologie Analytique, Faculté de Médecine Rockefeller, Université Claude Bernard Lyon I, Lyon, France.
11
Department of Hematology, Rzeszow Regional Hospital, Rzeszow, Poland.
12
Center for Translational Science Activities, Mayo Clinic, Rochester, MN, USA Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, USA.
13
Department of Hematology, Medical University of Lodz, Lodz, Poland.
14
Department of Hematology, Cracow University Hospital, Cracow, Poland.
15
Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
16
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.
17
Hematology Service, CRIS facility for Hematological research, Hospital Universitario 12 de Octubre, Universidad Complutense, Madrid, Spain.
18
Genomic Oncology Area, GENYO, Centre for Genomics and Oncological Research: Pfizer / University of Granada / Andalusian Regional Government, Granada, Spain; Hematology department, Virgen de las Nieves University Hospital, Granada, Spain.
19
Department of Hematology, Righospitalet and Roskilde Hospital, Copenhagen University, Denmark.
20
Department of Hematology, Holycross Cancer Center, Kielce, Poland.
21
Division of Biomedical Statistics and Informatics. Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA.
22
Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine Rochester, MN, USA.
#
Contributed equally

Abstract

Here we perform the first genome-wide association study (GWAS) of multiple myeloma (MM) survival. In a meta-analysis of 306 MM patients treated at UCSF and 239 patients treated at the Mayo clinic, we find a significant association between SNPs near the gene FOPNL on chromosome 16p13 and survival (rs72773978; P=6 × 10(-10)). Patients with the minor allele are at increased risk for mortality (HR: 2.65; 95% CI: 1.94-3.58) relative to patients homozygous for the major allele. We replicate the association in the IMMEnSE cohort including 772 patients, and a University of Utah cohort including 318 patients (rs72773978 P=0.044). Using publicly available data, we find that the minor allele was associated with increased expression of FOPNL and increased expression of FOPNL was associated with higher expression of centrosomal genes and with shorter survival. Polymorphisms at the FOPNL locus are associated with survival among MM patients.

PMID:
26198393
PMCID:
PMC4656791
DOI:
10.1038/ncomms8539
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center