Journal article
A Meta-analysis of Multiple Myeloma Risk Regions in African and European Ancestry Populations Identifies Putatively Functional Loci
Cancer epidemiology, biomarkers & prevention, v 25(12), pp 1609-1618
01 Dec 2016
PMID: 27587788
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Background: Genome-wide association studies (GWAS) in European populations have identified genetic risk variants associated with multiple myeloma.
Methods: We performed association testing of common variation in eight regions in 1,318 patients with multiple myeloma and 1,480 controls of European ancestry and 1,305 patients with multiple myeloma and 7,078 controls of African ancestry and conducted a meta-analysis to localize the signals, with epigenetic annotation used to predict functionality.
Results: We found that variants in 7p15.3, 17p11.2, 22q13.1 were statistically significantly (P < 0.05) associated with multiple myeloma risk in persons of African ancestry and persons of European ancestry, and the variant in 3p22.1 was associated in European ancestry only. In a combined African ancestry-European ancestry meta-analysis, variation in five regions (2p23.3, 3p22.1, 7p15.3, 17p11.2, 22q13.1) was statistically significantly associated with multiple myeloma risk. In 3p22.1, the correlated variants clustered within the gene body of ULK4. Correlated variants in 7p15.3 clustered around an enhancer at the 30 end of the CDCA7L transcription termination site. A missense variant at 17p11.2 (rs34562254, Pro251Leu, OR, 1.32; P = 2.93 x 10(-7)) in TNFRSF13B encodes a lymphocyte-specific protein in the TNF receptor family that interacts with the NF-kB pathway. SNPs correlated with the index signal in 22q13.1 cluster around the promoter and enhancer regions of CBX7.
Conclusions: We found that reported multiple myeloma susceptibility regions contain risk variants important across populations, supporting the use of multiple racial/ethnic groups with different underlying genetic architecture to enhance the localization and identification of putatively functional alleles.
Impact: A subset of reported risk loci for multiple myeloma has consistent effects across populations and is likely to be functional. Cancer Epidemiol Biomarkers Prev; 25(12); 1609-18. (C) 2016 AACR.
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Details
- Title
- A Meta-analysis of Multiple Myeloma Risk Regions in African and European Ancestry Populations Identifies Putatively Functional Loci
- Creators
- Kristin A. Rand - University of Southern CaliforniaChi Song - University of Southern CaliforniaEric Dean - Sutter HealthDaniel J. Serie - Mayo ClinicKaren Curtin - University of UtahXin Sheng - University of Southern CaliforniaDonglei Hu - University of California, San FranciscoCarol Ann Huff - Johns Hopkins UniversityLeon Bernal-Mizrachi - Emory UniversityMichael H. Tomasson - Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, St Louis, MO USASikander Ailawadhi - Mayo ClinicSeema Singhal - Northwestern UniversityKaren Pawlish - New Jersey Dept Hlth, New Jersey State Canc Registry, Trenton, NJ USAEdward S. Peters - Louisiana State UniversityCathryn H. Bock - Wayne State UniversityAlex Stram - Genom Hlth Inc, Redwood City, CA USADavid J. Van den Berg - University of Southern CaliforniaChristopher K. Edlund - University of Southern CaliforniaDavid V. Conti - University of Southern CaliforniaTodd Zimmerman - University of ChicagoAmie E. Hwang - University of Southern CaliforniaScott Huntsman - University of California, San FranciscoJohn Graff - Rutgers, The State University of New JerseyAjay Nooka - Emory UniversityYinfei Kong - University of Southern CaliforniaSilvana L. Pregja - Wayne State UniversitySonja I. Berndt - National Institutes of HealthWilliam J. Blot - Vanderbilt UniversityJohn Carpten - Translational Genomics Research InstituteGraham Casey - University of Southern CaliforniaLisa Chu - Stanford UniversityW. Ryan Diver - American Cancer SocietyVictoria L. Stevens - American Cancer SocietyMichael R. Lieber - University of Southern CaliforniaPhyllis J. Goodman - SWOG Stat Ctr, Seattle, WA USAAnselm J. M. Hennis - SUNY Stony Brook, Stony Brook, NY 11794 USAAnn W. Hsing - Stanford UniversityJayesh Mehta - Northwestern UniversityRick A. Kittles - University of ArizonaSuzanne Kolb - Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South AfricaEric A. Klein - Cleveland Clin, Glickman Urol & Kidney Inst, Cleveland, OH 44106 USACristina Leske - Stony Brook UniversityAdam B. Murphy - Northwestern UniversityBarbara Nemesure - Stony Brook UniversityChristine Neslund-Dudas - Henry Ford Health SystemSara S. Strom - The University of Texas MD Anderson Cancer CenterRavi Vij - Washington University in St. LouisBenjamin A. Rybicki - Henry Ford Health SystemJanet L. Stanford - Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South AfricaLisa B. Signorello - Harvard UniversityJohn S. Witte - University of California, San FranciscoChristine B. Ambrosone - Roswell Park Cancer InstituteParveen Bhatti - Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South AfricaEsther M. John - Stanford UniversityLeslie Bernstein - City Of Hope National Medical CenterWei Zheng - Int Epidemiol Inst, Rockville, MD USAAndrew F. Olshan - University of North Carolina at Chapel HillJennifer J. Hu - University of MiamiRegina G. Ziegler - National Institutes of HealthSarah J. Nyante - University of North Carolina at Chapel HillElisa V. Bandera - Rutgers, The State University of New JerseyBrenda M. Birmann - Harvard UniversitySue A. Ingles - University of Southern CaliforniaMichael F. Press - University of Southern CaliforniaDjordje Atanackovic - University of UtahMartha J. Glenn - University of UtahLisa A. Cannon-Albright - University of UtahBrandt Jones - University of UtahGuido Tricot - University of IowaThomas G. Martin - University of California, San FranciscoShaji K. Kumar - Mayo ClinicJeffrey L. Wolf - University of California, San FranciscoSandra L. Deming Halverson - Int Epidemiol Inst, Rockville, MD USANathaniel Rothman - National Institutes of HealthAngela R. Brooks-Wilson - University of British ColumbiaS. Vincent Rajkumar - Mayo ClinicLaurence N. Kolonel - Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USAStephen J. Chanock - National Institutes of HealthSusan L. Slager - Mayo ClinicRichard K. Severson - Wayne State UniversityNalini Janakiraman - Henry Ford Health SystemHoward R. Terebelo - St. John Providence Health SystemElizabeth E. Brown - University of Alabama at BirminghamAnneclaire J. De Roos - Drexel UniversityAnn F. Mohrbacher - University of Southern CaliforniaGraham A. Colditz - Washington University in St. LouisGraham G. Giles - Monash UniversityJohn J. Spinelli - University of British ColumbiaBrian C. Chiu - University of ChicagoNikhil C. Munshi - Harvard UniversityKenneth C. Anderson - Harvard UniversityJoan Levy - Multiple Myeloma Research FoundationJeffrey A. Zonder - Wayne State UniversityRobert Z. Orlowski - The University of Texas MD Anderson Cancer CenterSagar Lonial - Emory UniversityNicola J. Camp - University of UtahCeline M. Vachon - Mayo ClinicElad Ziv - University of California, San FranciscoDaniel O. Stram - University of Southern CaliforniaDennis J. Hazelett - Cedars-Sinai Medical CenterChristopher A. Haiman - University of Southern CaliforniaWendy Cozen - University of Southern California
- Publication Details
- Cancer epidemiology, biomarkers & prevention, v 25(12), pp 1609-1618
- Publisher
- Amer Assoc Cancer Research
- Number of pages
- 10
- Grant note
- LLS 6067-090 / Leukemia Lymphoma Society; Leukemia and Lymphoma Society Intramural Program of the National Human Genome Research Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI) N01-PC-35139 / NCI, NIH, Department of Health and Human Services; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) CA68485 / Vanderbilt-Ingram Cancer Center IRG60-001-47 / American Cancer Society CA63464; CA54281; CA1326792; CA148085; HG004726; CA056678; CA082664; CA092579; ES011126 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01-CA100598 / WCHS [NIH]; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA 99- 00524V10258; 9712013 / Cancer Research Fund 261201300021I; N01PC-2013 00021; HHSN261201000026C / HHSN Department of Health Services Cancer Research Program P50-CA58223 / CBCS (NIH Specialized Program of Research Excellence in Breast Cancer); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA P01-CA151135; U19-CA148065 / Norris Foundation U01-CA69417 / NC-BCFR (NIH); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA 5U58DP003931-02; 1U58DP000807-01 / National Program of Cancer Registries of the Centers for Disease Control and Prevention DAMD-17-01-0-0334 / WCHS [U.S. Army Medical Research and Material Command (USAMRMC)]; U.S. Army Medical Research & Materiel Command (USAMRMC) 98-00924V / University of California; University of California System R01-CA77305 / SFBCS (NIH); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA P30-ES10126 / Center for Environmental Health and Susceptibility National Institute of Environmental Health Sciences, NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS) 103885 / California Department of Health Services R01-CA63464; R37-CA54281; UM1-CA164973 / MEC (NIH) PLCO (Intramural Research Program, National Cancer Institute, NIH) P30ES010126 / NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS) R35GM118009 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) Fred Hutchinson Cancer Research Center P30CA014089 / USC Norris Comprehensive Cancer Center Core grant from the National Cancer Institute RFA-CA-06-503 / National Cancer Institute, NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) U01HG004726 / NATIONAL HUMAN GENOME RESEARCH INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI) Intramural Research Program of the Division of Cancer Epidemiology and Genetics, NCI, NIH Huntsman Cancer Institute (HCI) P30 CA42014 / HCI Cancer Center Support grant WCHS [Breast Cancer Research Foundation] R01-CA100374 / NBHS (National Institutes of Health); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA U58DP003931 / NATIONAL CENTER FOR CHRONIC DISEASE PREV AND HEALTH PROMO; United States Department of Health & Human Services; Centers for Disease Control & Prevention - USA 1R01CA134786; 2P50CA100707; Myeloma SPORE 2P50CA100707 Project; R01CA152336; R01CA134674; P50 CA142509; R01CA184464; R21CA155951; R25CA76023; R01CA186646; U54CA118948; P30CA13148; R21CA191896; K24CA169004 / National Cancer Institute at the NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) N01-PC-35139 / National Cancer Institute Surveillance Epidemiology and End Results Population-based Registry Program, NIH, Department of Health and Human Services U10 CA37429; UM1 CA182883 / Public Health Service from the National Cancer Institute NO1-HD-3-3175; K05 CA136967 / CARE (National Institute for Child Health and Development); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) R01-CA73629 / WFBC (NIH); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Steve and Nancy Grand Multiple Myeloma Translational Initiative W81XWH-08-1-0383 / Department of Defense Breast Cancer Research Program Era of Hope Scholar Award; United States Department of Defense R21CA191896 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) DAMD17-96-6071 / SFBCS (United States Army Medical Research Program)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Environmental and Occupational Health
- Web of Science ID
- WOS:000389704300009
- Scopus ID
- 2-s2.0-85006255902
- Other Identifier
- 991019168853204721
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- Web of Science research areas
- Oncology
- Public, Environmental & Occupational Health