Publication

A Meta-analysis of Multiple Myeloma Risk Regions in African and European Ancestry Populations Identifies Putatively Functional Loci

Downloadable Content

Persistent URL
Last modified
  • 03/05/2025
Type of Material
Authors
    Kristin A. Rand, University of Southern CaliforniaChi Song, University of Southern CaliforniaEric Dean, Sutter HealthDaniel J. Serie, Mayo Clinic, JacksonvilleKaren 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 UniversitySikander Ailawadhi, Mayo Clinic, JacksonvilleSeema Singhal, Northwestern UniversityKaren Pawlish, New Jersey Department of HealthEdward S. Peters, Louisiana State UniversityCathryn H. Bock, Wayne State UniversityAlex Stram, Genomic Health, Inc.David 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 State UniversityAjay Nooka, Emory UniversityYinfei Kong, University of Southern CaliforniaSilvana L. Pregja, Wayne State UniversitySonja Berndt, National Institutes of HealthWilliam J. Blot, International Epidemiology InstituteJohn Carpten, The Translational Genomics Research InstituteGraham Casey, University of Southern CaliforniaLisa Chu, Cancer Prevention Institute of CaliforniaW. Ryan Diver, American Cancer SocietyVictoria L. Stevens, American Cancer SocietyMichael R. Lieber, University of Southern CaliforniaPhyllis J. Goodman, SWOG Statistical CenterAnselm J.M. Hennis, Stony Brook UniversityAnn W. Hsing, Stanford UniversityJayesh Mehta, Northwestern UniversityRick A. Kittles, University of ArizonaSuzanne Kolb, Fred Hutchinson Cancer Research CenterEric A. Klein, Cleveland ClinicCristina Leske, Stony Brook UniversityAdam B. Murphy, Northwestern UniversityBarbara Nemesure, Stony Brook UniversityChristine Neslund-Dudas, Henry Ford HospitalSara S. Strom, The University of Texas MD Anderson Cancer CenterRavi Vij, Washington UniversityBenjamin A. Rybicki, Henry Ford HospitalJanet L. Stanford, Fred Hutchinson Cancer Research CenterLisa B. Signorello, Harvard UniversityJohn S. Witte, University of California San FranciscoChristine B. Ambrosone, Roswell Park Cancer InstituteParveen Bhatti, Fred Hutchinson Cancer Research CenterEsther M. John, Cancer Prevention Institute of CaliforniaLeslie Bernstein, Beckman Research Institute of the City of HopeWei Zheng, International Epidemiology InstituteAndrew F. Olshan, University of North CarolinaJennifer J. Hu, University of MiamiRegina C. Ziegler, National Institutes of HealthSarah J. Nyante, University of North CarolinaElisa V. Bandera, Rutgers State UniversityBrenda 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. Halverson, International Epidemiology InstituteNathaniel Rothman, National Institutes of HealthAngela R. Brooks-Wilson, BC Cancer AgencyS. Vincent Rajkumar, Mayo ClinicLaurence N. Kolonel, University of HawaiiStephen J. Chanock, National Institutes of HealthSusan L. Slager, Mayo ClinicRichard K. Severson, Wayne State UniversityNalini Janakiraman, Henry Ford HospitalHoward R. Terebelo, Providence HospitalElizabeth E. Brown, University of Alabama BirminghamAnneclaire J. De Roos, Drexel UniversityAnn F. Mohrbacher, University of Southern CaliforniaGraham A. Colditz, Washington UniversityGraham G. Giles, Cancer Council of VictoriaJohn J. Spinelli, BC Cancer AgencyBrian 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
Language
  • English
Date
  • 2016-12-01
Publisher
  • American Association for Cancer Research
Publication Version
Copyright Statement
  • © 2016 AACR.
Final Published Version (URL)
Title of Journal or Parent Work
ISSN
  • 1055-9965
Volume
  • 25
Issue
  • 12
Start Page
  • 1609
End Page
  • 1618
Grant/Funding Information
  • The collection of patients used in this publication was supported in part by the California Department of Health Services as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885.
  • See publication for additional funding related specifically to AAPC and AABC studies.
  • Additional support for collection of incident multiple myeloma patient data was obtained from the Utah State Department of Health and the University of Utah, the Utah Population Database (UPDB) and the Utah Cancer Registry (UCR), the National Program of Cancer Registries of the Centers for Disease Control and Prevention (5U58DP003931-02 to the New Jersey State Cancer Registry and 1U58DP000807-01 to the California Cancer Registry, the Huntsman Cancer Institute (HCI) and the HCI Cancer Center Support grant, P30 CA42014 and by the USC Norris Comprehensive Cancer Center Core grant P30CA014089 from the National Cancer Institute.
  • Data collection from the cancer registries was supported by the National Cancer Institute Surveillance Epidemiology and End Results Population-based Registry Program, National Institutes of Health, Department of Health and Human Services, under contracts N01-PC-35139 (to USC for Los Angeles County), HHSN 261201300021I, N01PC-2013-00021 (to the New Jersey State Cancer Registry), and HHSN261201000026C (to the Utah Cancer Registry).
  • This study was supported by the National Cancer Institute at the National Institutes of Health (1R01CA134786 to WC and CAH, 2P50CA100707 to KCA, Myeloma SPORE 2P50CA100707 Project 6 to KCA, WC and DVC, R01CA152336 and R01CA134674 to NC, P50 CA142509 and R01CA184464 to RZO, R21CA155951, R25CA76023, R01CA186646, U54CA118948 Project 3 and P30CA13148 (seed grant) to EEB, and R21CA191896 and K24CA169004 to EZ).
  • The study also received support from the Leukemia Lymphoma Society (LLS 6067-090) to NC, the American Cancer Society (IRG60-001-47) to EEB, and the Steve and Nancy Grand Multiple Myeloma Translational Initiative to EZ.
Supplemental Material (URL)
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 × 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.
Author Notes
  • Correspondence to: Wendy Cozen, USC Norris Comprehensive Cancer Center, Topping Tower, 1441 Eastlake Ave, Room 4451A, Los Angeles, CA 90033, Telephone: (323) 865-0447, Fax: (323) 865-0141, wcozen@usc.edu; or; Christopher A. Haiman, USC Norris Comprehensive Cancer Center, Harlyne Norris Research Tower, 1450 Biggy Street, Room 1504, Los Angeles, CA 90033, Telephone: (323) 442-7755, Fax: (323) 442-7749, haiman@usc.edu; or; Dennis Hazelett, Samuel Oschin Comprehensive Cancer Institute, CedarsSinai Medical Center 8700 Beverly Blvd. Los Angeles, CA 90048, Telephone: (310) 424-315-4412, Fax: (310) 273-9533, Dennis.Hazelett@csmc.edu.
Keywords
Research Categories
  • Health Sciences, Oncology
  • Health Sciences, General

Tools

Relations

In Collection:

Items

Thumbnail Title File Description Date Uploaded Visibility Actions
file details Publication File - s6r1m.pdf Primary Content 2025-03-04 Public Download