Blood Advances (Jan 2020)
A meta-analysis of genome-wide association studies of multiple myeloma among men and women of African ancestry
- Zhaohui Du,
- Niels Weinhold,
- Gregory Chi Song,
- Kristin A. Rand,
- David J. Van Den Berg,
- Amie E. Hwang,
- Xin Sheng,
- Victor Hom,
- Sikander Ailawadhi,
- Ajay K. Nooka,
- Seema Singhal,
- Karen Pawlish,
- Edward S. Peters,
- Cathryn Bock,
- Ann Mohrbacher,
- Alexander Stram,
- Sonja I. Berndt,
- William J. Blot,
- Graham Casey,
- Victoria L. Stevens,
- Rick Kittles,
- Phyllis J. Goodman,
- W. Ryan Diver,
- Anselm Hennis,
- Barbara Nemesure,
- Eric A. Klein,
- Benjamin A. Rybicki,
- Janet L. Stanford,
- John S. Witte,
- Lisa Signorello,
- Esther M. John,
- Leslie Bernstein,
- Antoinette M. Stroup,
- Owen W. Stephens,
- Maurizio Zangari,
- Frits Van Rhee,
- Andrew Olshan,
- Wei Zheng,
- Jennifer J. Hu,
- Regina Ziegler,
- Sarah J. Nyante,
- Sue Ann Ingles,
- Michael F. Press,
- John David Carpten,
- Stephen J. Chanock,
- Jayesh Mehta,
- Graham A. Colditz,
- Jeffrey Wolf,
- Thomas G. Martin,
- Michael Tomasson,
- Mark A. Fiala,
- Howard Terebelo,
- Nalini Janakiraman,
- Laurence Kolonel,
- Kenneth C. Anderson,
- Loic Le Marchand,
- Daniel Auclair,
- Brian C.-H. Chiu,
- Elad Ziv,
- Daniel Stram,
- Ravi Vij,
- Leon Bernal-Mizrachi,
- Gareth J. Morgan,
- Jeffrey A. Zonder,
- Carol Ann Huff,
- Sagar Lonial,
- Robert Z. Orlowski,
- David V. Conti,
- Christopher A. Haiman,
- Wendy Cozen
Affiliations
- Zhaohui Du
- Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA;
- Niels Weinhold
- Myeloma Center, University of Arkansas for Medical Sciences, Little Rock, AR;
- Gregory Chi Song
- Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA;
- Kristin A. Rand
- Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA;
- David J. Van Den Berg
- Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA;
- Amie E. Hwang
- Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA;
- Xin Sheng
- Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA;
- Victor Hom
- Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA;
- Sikander Ailawadhi
- Division of Hematology-Oncology, Mayo Clinic, Jacksonville, FL;
- Ajay K. Nooka
- Winship Cancer Institute, Department of Hematology and Medical Oncology, Emory University, Atlanta, GA;
- Seema Singhal
- Division of Hematology-Oncology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL;
- Karen Pawlish
- Cancer Epidemiology Services, Epidemiology, Environmental and Occupational Health Division, New Jersey Department of Health, Trenton, NJ;
- Edward S. Peters
- Department of Epidemiology, Louisiana State University School of Public Health, New Orleans, LA;
- Cathryn Bock
- Karmanos Cancer Center, Wayne State University, Detroit, MI;
- Ann Mohrbacher
- Division of Hematology, Department of Medicine, University of Southern California, Los Angeles, CA;
- Alexander Stram
- Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA;
- Sonja I. Berndt
- Division of Cancer Genetics and Epidemiology, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD;
- William J. Blot
- Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN;
- Graham Casey
- Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA;
- Victoria L. Stevens
- American Cancer Society, Atlanta, GA;
- Rick Kittles
- City of Hope National Medical Center, Duarte, CA;
- Phyllis J. Goodman
- The Southwest Oncology Group Statistical Center, Seattle, WA;
- W. Ryan Diver
- American Cancer Society, Atlanta, GA;
- Anselm Hennis
- Department of Preventive Medicine, Stony Brook University, Stony Brook, NY;
- Barbara Nemesure
- Department of Preventive Medicine, Stony Brook University, Stony Brook, NY;
- Eric A. Klein
- Cleveland Clinic Foundation, Cleveland, OH;
- Benjamin A. Rybicki
- Henry Ford Hospital, Detroit, MI;
- Janet L. Stanford
- Fred Hutchinson Cancer Center, Seattle, WA;
- John S. Witte
- Department of Epidemiology and Biostatistics, University of California, San Francisco, CA;
- Lisa Signorello
- Division of Cancer Genetics and Epidemiology, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD;
- Esther M. John
- Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA;
- Leslie Bernstein
- City of Hope National Medical Center, Duarte, CA;
- Antoinette M. Stroup
- Cancer Epidemiology Services, Epidemiology, Environmental and Occupational Health Division, New Jersey Department of Health, Trenton, NJ;; Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Rutgers University, New Brunswick, NJ;
- Owen W. Stephens
- Myeloma Center, University of Arkansas for Medical Sciences, Little Rock, AR;
- Maurizio Zangari
- Myeloma Center, University of Arkansas for Medical Sciences, Little Rock, AR;
- Frits Van Rhee
- Myeloma Center, University of Arkansas for Medical Sciences, Little Rock, AR;
- Andrew Olshan
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC;
- Wei Zheng
- Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN;
- Jennifer J. Hu
- Department of Public Health Sciences, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL;
- Regina Ziegler
- Division of Cancer Genetics and Epidemiology, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD;
- Sarah J. Nyante
- Department of Radiology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC;
- Sue Ann Ingles
- Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA;
- Michael F. Press
- Department of Pathology, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA;
- John David Carpten
- Center for Translational Genomics, Department of Translational Genomics, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA;
- Stephen J. Chanock
- Division of Cancer Genetics and Epidemiology, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD;
- Jayesh Mehta
- Division of Hematology-Oncology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL;
- Graham A. Colditz
- Division of Oncology, Washington University School of Medicine, Saint Louis, MO;
- Jeffrey Wolf
- Department of Epidemiology and Biostatistics, University of California, San Francisco, CA;
- Thomas G. Martin
- Department of Epidemiology and Biostatistics, University of California, San Francisco, CA;
- Michael Tomasson
- Division of Hematology, Oncology and Bone Marrow Transplantation, Department of Internal Medicine, University of Iowa, Iowa City, IA;
- Mark A. Fiala
- Division of Oncology, Washington University School of Medicine, Saint Louis, MO;
- Howard Terebelo
- Providence Hospital, Southfield, MI;
- Nalini Janakiraman
- Division of Hematology-Oncology, Henry Ford Hospital, Detroit, MI;
- Laurence Kolonel
- University of Hawaii Cancer Center, Honolulu, HI;
- Kenneth C. Anderson
- J. Lipper Cancer Center for Multiple Myeloma, Dana-Farber Cancer Institute, Harvard University, Boston, MA;
- Loic Le Marchand
- University of Hawaii Cancer Center, Honolulu, HI;
- Daniel Auclair
- Multiple Myeloma Research Foundation, Norwalk, CT;
- Brian C.-H. Chiu
- Department of Public Health Sciences, University of Chicago, Chicago, IL;
- Elad Ziv
- Department of Epidemiology and Biostatistics, University of California, San Francisco, CA;
- Daniel Stram
- Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA;
- Ravi Vij
- Division of Oncology, Washington University School of Medicine, Saint Louis, MO;
- Leon Bernal-Mizrachi
- Grady Memorial Hospital, Emory University, Atlanta, GA;
- Gareth J. Morgan
- Myeloma Center, Perlmutter Cancer Center, New York University, New York, NY;
- Jeffrey A. Zonder
- Karmanos Cancer Center, Wayne State University, Detroit, MI;
- Carol Ann Huff
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD
- Sagar Lonial
- Winship Cancer Institute, Department of Hematology and Medical Oncology, Emory University, Atlanta, GA;
- Robert Z. Orlowski
- Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX
- David V. Conti
- Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA;
- Christopher A. Haiman
- Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA;
- Wendy Cozen
- Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA;; Department of Pathology, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA;; Wendy Cozen, Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, 1441 Eastlake Ave, MC 9175, Los Angeles, CA 90089-9175;
- Journal volume & issue
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Vol. 4,
no. 1
pp. 181 – 190
Abstract
Abstract: Persons of African ancestry (AA) have a twofold higher risk for multiple myeloma (MM) compared with persons of European ancestry (EA). Genome-wide association studies (GWASs) support a genetic contribution to MM etiology in individuals of EA. Little is known about genetic risk factors for MM in individuals of AA. We performed a meta-analysis of 2 GWASs of MM in 1813 cases and 8871 controls and conducted an admixture mapping scan to identify risk alleles. We fine-mapped the 23 known susceptibility loci to find markers that could better capture MM risk in individuals of AA and constructed a polygenic risk score (PRS) to assess the aggregated effect of known MM risk alleles. In GWAS meta-analysis, we identified 2 suggestive novel loci located at 9p24.3 and 9p13.1 at P < 1 × 10−6; however, no genome-wide significant association was noted. In admixture mapping, we observed a genome-wide significant inverse association between local AA at 2p24.1-23.1 and MM risk in AA individuals. Of the 23 known EA risk variants, 20 showed directional consistency, and 9 replicated at P < .05 in AA individuals. In 8 regions, we identified markers that better capture MM risk in persons with AA. AA individuals with a PRS in the top 10% had a 1.82-fold (95% confidence interval, 1.56-2.11) increased MM risk compared with those with average risk (25%-75%). The strongest functional association was between the risk allele for variant rs56219066 at 5q15 and lower ELL2 expression (P = 5.1 × 10−12). Our study shows that common genetic variation contributes to MM risk in individuals with AA.
