A meta-analysis of genome-wide association studies of multiple myeloma among men and women of African ancestry.

Autor: Du Z; Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA., Weinhold N; Myeloma Center, University of Arkansas for Medical Sciences, Little Rock, AR., Song GC; Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA., Rand KA; Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA., Van Den Berg DJ; Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA., Hwang AE; Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA., Sheng X; Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA., Hom V; Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA., Ailawadhi S; Division of Hematology-Oncology, Mayo Clinic, Jacksonville, FL., Nooka AK; Winship Cancer Institute, Department of Hematology and Medical Oncology, Emory University, Atlanta, GA., Singhal S; Division of Hematology-Oncology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL., Pawlish K; Cancer Epidemiology Services, Epidemiology, Environmental and Occupational Health Division, New Jersey Department of Health, Trenton, NJ., Peters ES; Department of Epidemiology, Louisiana State University School of Public Health, New Orleans, LA., Bock C; Karmanos Cancer Center, Wayne State University, Detroit, MI., Mohrbacher A; Division of Hematology, Department of Medicine, University of Southern California, Los Angeles, CA., Stram A; Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA., Berndt SI; Division of Cancer Genetics and Epidemiology, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD., Blot WJ; Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN., Casey G; Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA., Stevens VL; American Cancer Society, Atlanta, GA., Kittles R; City of Hope National Medical Center, Duarte, CA., Goodman PJ; The Southwest Oncology Group Statistical Center, Seattle, WA., Diver WR; American Cancer Society, Atlanta, GA., Hennis A; Department of Preventive Medicine, Stony Brook University, Stony Brook, NY., Nemesure B; Department of Preventive Medicine, Stony Brook University, Stony Brook, NY., Klein EA; Cleveland Clinic Foundation, Cleveland, OH., Rybicki BA; Henry Ford Hospital, Detroit, MI., Stanford JL; Fred Hutchinson Cancer Center, Seattle, WA., Witte JS; Department of Epidemiology and Biostatistics, University of California, San Francisco, CA., Signorello L; Division of Cancer Genetics and Epidemiology, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD., John EM; Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA., Bernstein L; City of Hope National Medical Center, Duarte, CA., Stroup AM; 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., Stephens OW; Myeloma Center, University of Arkansas for Medical Sciences, Little Rock, AR., Zangari M; Myeloma Center, University of Arkansas for Medical Sciences, Little Rock, AR., Van Rhee F; Myeloma Center, University of Arkansas for Medical Sciences, Little Rock, AR., Olshan A; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC., Zheng W; Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN., Hu JJ; Department of Public Health Sciences, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL., Ziegler R; Division of Cancer Genetics and Epidemiology, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD., Nyante SJ; Department of Radiology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC., Ingles SA; Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA., Press MF; Department of Pathology, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA., Carpten JD; Center for Translational Genomics, Department of Translational Genomics, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA., Chanock SJ; Division of Cancer Genetics and Epidemiology, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD., Mehta J; Division of Hematology-Oncology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL., Colditz GA; Division of Oncology, Washington University School of Medicine, Saint Louis, MO., Wolf J; Department of Epidemiology and Biostatistics, University of California, San Francisco, CA., Martin TG; Department of Epidemiology and Biostatistics, University of California, San Francisco, CA., Tomasson M; Division of Hematology, Oncology and Bone Marrow Transplantation, Department of Internal Medicine, University of Iowa, Iowa City, IA., Fiala MA; Division of Oncology, Washington University School of Medicine, Saint Louis, MO., Terebelo H; Providence Hospital, Southfield, MI., Janakiraman N; Division of Hematology-Oncology, Henry Ford Hospital, Detroit, MI., Kolonel L; University of Hawaii Cancer Center, Honolulu, HI., Anderson KC; J. Lipper Cancer Center for Multiple Myeloma, Dana-Farber Cancer Institute, Harvard University, Boston, MA., Le Marchand L; University of Hawaii Cancer Center, Honolulu, HI., Auclair D; Multiple Myeloma Research Foundation, Norwalk, CT., Chiu BC; Department of Public Health Sciences, University of Chicago, Chicago, IL., Ziv E; Department of Epidemiology and Biostatistics, University of California, San Francisco, CA., Stram D; Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA., Vij R; Division of Oncology, Washington University School of Medicine, Saint Louis, MO., Bernal-Mizrachi L; Grady Memorial Hospital, Emory University, Atlanta, GA., Morgan GJ; Myeloma Center, Perlmutter Cancer Center, New York University, New York, NY., Zonder JA; Karmanos Cancer Center, Wayne State University, Detroit, MI., Huff CA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD; and., Lonial S; Winship Cancer Institute, Department of Hematology and Medical Oncology, Emory University, Atlanta, GA., Orlowski RZ; Department of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX., Conti DV; Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA., Haiman CA; Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA., Cozen W; 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.
Jazyk: angličtina
Zdroj: Blood advances [Blood Adv] 2020 Jan 14; Vol. 4 (1), pp. 181-190.
DOI: 10.1182/bloodadvances.2019000491
Abstrakt: 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.
Databáze: MEDLINE