A meta-analysis of multiple myeloma risk regions in African and European ancestry populations identifies putatively functional loci

Details

• Alternative Title:
  Cancer Epidemiol Biomarkers Prev
• Personal Author:
  Rand, Kristin A. ; Song, Chi ; Dean, Eric ; Serie, Daniel J. ; Curtin, Karen ; Sheng, Xin ; Hu, Donglei ; Huff, Carol Ann ; Bernal-Mizrachi, Leon ; Tomasson, Michael H. ; Ailawadhi, Sikander ; Singhal, Seema ; Pawlish, Karen ; Peters, Edward S. ; Bock, Cathryn H. ; Stram, Alex ; Van Den Berg, David J ; Edlund, Christopher K. ; V.Conti, David ; Zimmerman, Todd ; Hwang, Amie E. ; Huntsman, Scott ; Graff, John ; Nooka, Ajay ; Kong, Yinfei ; Pregja, Silvana L. ; Berndt, Sonja I. ; Blot, William J. ; Carpten, John ; Casey, Graham ; Chu, Lisa ; Diver, W. Ryan ; Stevens, Victoria L. ; Lieber, Michael R. ; Goodman, Phyllis J. ; Hennis, Anselm J.M. ; Hsing, Ann W. ; Mehta, Jayesh ; Kittles, Rick A. ; Kolb, Suzanne ; Klein, Eric A. ; Leske, Cristina ; Murphy, Adam B. ; Nemesure, Barbara ; Neslund-Dudas, Christine ; Strom, Sara S. ; Vij, Ravi ; Rybicki, Benjamin A. ; Stanford, Janet L. ; Signorello, Lisa B. ; Witte, John S. ; Ambrosone, Christine B. ; Bhatti, Parveen ; John, Esther M. ; Bernstein, Leslie ; Zheng, Wei ; Olshan, Andrew F. ; Hu, Jennifer J. ; Ziegler, Regina G. ; Nyante, Sarah J. ; Bandera, Elisa V. ; Birmann, Brenda M. ; Ingles, Sue A. ; Press, Michael F. ; Atanackovic, Djordje ; Glenn, Martha J. ; Cannon-Albright, Lisa A. ; Jones, Brandt ; Tricot, Guido ; Martin, Thomas G. ; Kumar, Shaji K. ; Wolf, Jeffrey L. ; Deming, Sandra L. ; Rothman, Nathaniel ; Brooks-Wilson, Angela R. ; Rajkumar, S. Vincent ; Kolonel, Laurence N. ; Chanock, Stephen J. ; Slager, Susan L. ; Severson, Richard K. ; Janakiraman, Nalini ; Terebelo, Howard R. ; Brown, Elizabeth E. ; De Roos, Anneclaire J. ; Mohrbacher, Ann F. ; Colditz, Graham A. ; Giles, Graham G. ; Spinelli, John J. ; Chiu, Brian C. ; Munshi, Nikhil C. ; Anderson, Kenneth C. ; Levy, Joan ; Zonder, Jeffrey A. ; Orlowski, Robert Z. ; Lonial, Sagar ; Camp, Nicola J. ; Vachon, Celine M. ; Ziv, Elad ; Stram, Daniel O. ; Hazelett, Dennis J. ; Haiman, Christopher A. ; Cozen, Wendy
• Description:
  Background
  
  Genome-wide association studies (GWAS) in European populations have identified genetic risk variants associated with multiple myeloma (MM).
  
  Methods
  
  We performed association testing of common variation in eight regions in 1,264 MM patients and 1,479 controls of European ancestry (EA) and 1,305 MM patients and 7,078 controls of African ancestry (AA) 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 MM risk in AAs and EAs and the variant in 3p22.1 was associated in EAs only. In a combined AA-EA meta-analysis, variation in five regions (2p23.3, 3p22.1, 7p15.3, 17p11.2, 22q13.1) was statistically signficantly associated with MM 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 3′ 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 tumor necrosis factor receptor family that interacts with the NF-κB pathway. SNPs correlated with the index signal in 22q13.1 cluster around the promoter and enhancer regions of CBX7.
  
  Conclusions
  
  We found that reported MM 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 have consistent affects across populations and are likely to be functional.
  
  
• Keywords:
  Adult African-American Aged Black People Female Genetic Epidemiology Genetic Loci Genetic Predisposition To Disease Genome-Wide Association Study GWAS Humans Male Meta-analysis Middle Aged Multiple Myeloma Polycomb Repressive Complex 1 Polymorphism, Single Nucleotide Protein Serine-Threonine Kinases Repressor Proteins Transmembrane Activator And CAML Interactor Protein White People

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• Source:
  Cancer Epidemiol Biomarkers Prev. 25(12):1609-1618
• Pubmed ID:
  27587788
• Pubmed Central ID:
  PMC5524541
• Document Type:
  Journal Article
• Funding:
  R01 CA100504/CA/NCI NIH HHSUnited States/ ; R21 CA152336/CA/NCI NIH HHSUnited States/ ; U10 CA037429/CA/NCI NIH HHSUnited States/ ; U54 CA118948/CA/NCI NIH HHSUnited States/ ; P30 CA086862/CA/NCI NIH HHSUnited States/ ; P30 CA013148/CA/NCI NIH HHSUnited States/ ; R01 CA056678/CA/NCI NIH HHSUnited States/ ; R25 CA076023/CA/NCI NIH HHSUnited States/ ; R01 CA184464/CA/NCI NIH HHSUnited States/ ; P50 CA100707/CA/NCI NIH HHSUnited States/ ; U19 CA148065/CA/NCI NIH HHSUnited States/ ; R01 ES011126/ES/NIEHS NIH HHSUnited States/ ; U58 DP003931/DP/NCCDPHP CDC HHSUnited States/ ; U01 CA069417/CA/NCI NIH HHSUnited States/ ; R21 CA191896/CA/NCI NIH HHSUnited States/ ; P30 ES010126/ES/NIEHS NIH HHSUnited States/ ; RC2 CA148085/CA/NCI NIH HHSUnited States/ ; UM1 CA164973/CA/NCI NIH HHSUnited States/ ; R01 CA134786/CA/NCI NIH HHSUnited States/ ; P50 CA140388/CA/NCI NIH HHSUnited States/ ; P50 CA142509/CA/NCI NIH HHSUnited States/ ; R01 CA196671/CA/NCI NIH HHSUnited States/ ; U01 CA127298/CA/NCI NIH HHSUnited States/ ; UG1 CA189974/CA/NCI NIH HHSUnited States/ ; P01 CA151135/CA/NCI NIH HHSUnited States/ ; R01 CA073629/CA/NCI NIH HHSUnited States/ ; R21 CA155951/CA/NCI NIH HHSUnited States/ ; P50 CA058223/CA/NCI NIH HHSUnited States/ ; R01 CA068578/CA/NCI NIH HHSUnited States/ ; R01 CA100374/CA/NCI NIH HHSUnited States/ ; U58 DP000807/DP/NCCDPHP CDC HHSUnited States/ ; P50 CA186781/CA/NCI NIH HHSUnited States/ ; R01 CA186646/CA/NCI NIH HHSUnited States/ ; P30 CA014089/CA/NCI NIH HHSUnited States/ ; K05 CA136967/CA/NCI NIH HHSUnited States/ ; R01 CA063464/CA/NCI NIH HHSUnited States/ ; HHSN261201300021C/CA/NCI NIH HHSUnited States/ ; R01 CA082664/CA/NCI NIH HHSUnited States/ ; P30 ES007784/ES/NIEHS NIH HHSUnited States/ ; R01 CA054281/CA/NCI NIH HHSUnited States/ ; U01 CA063464/CA/NCI NIH HHSUnited States/ ; P30 CA068485/CA/NCI NIH HHSUnited States/ ; R01 CA088164/CA/NCI NIH HHSUnited States/ ; R01 CA092579/CA/NCI NIH HHSUnited States/ ; R01 CA134674/CA/NCI NIH HHSUnited States/ ; UM1 CA182883/CA/NCI NIH HHSUnited States/ ; N01PC35139/CA/NCI NIH HHSUnited States/ ; HHSN261201000026C/CA/NCI NIH HHSUnited States/ ; R37 CA054281/CA/NCI NIH HHSUnited States/ ; K24 CA169004/CA/NCI NIH HHSUnited States/ ; P30 CA042014/CA/NCI NIH HHSUnited States/ ; R35 GM118009/GM/NIGMS NIH HHSUnited States/ ; U01 HG004726/HG/NHGRI NIH HHSUnited States/ ; R01 CA100598/CA/NCI NIH HHSUnited States/
• Volume:
  25
• Issue:
  12
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:a12b678d7e83141b016553e38f652ab94daf923e4ef6b3a0da29184f6a60533a
• Download URL:
  https://stacks.cdc.gov/view/cdc/46892/cdc_46892_DS1.pdf
• File Type:
  [PDF - 530.65 KB ]