Abstract
Abstract 4629: Multiple myeloma susceptibility loci examined in African and European ancestry populations
Cancer research (Chicago, Ill.), Vol.75(15_Supplement), pp.4629-4629
08/01/2015
DOI: 10.1158/1538-7445.AM2015-4629
Abstract
Abstract
Genome-wide association studies (GWAS) of multiple myeloma (MM) in Northern Europeans have identified seven novel risk loci (2p23.3, 3p22.1, 3q26.2, 6p21.33, 7p15.3, 17p11.2, 22q13.1). We performed a multiethnic meta-analysis of these regions in 1,274 MM patients and 1,486 controls of European ancestry (EA) and 1,049 MM patients and 7,080 controls of African ancestry (AA), leveraging the differential linkage-disequilibrium of these populations in order to better localize the putative functional variants. We observed directionally consistent effects for all seven index SNPs in both populations, with four significantly associated (p<0.05) with risk in EAs (3p22.1, 7p15.3, 17p11.2, 22q13.1), and two significantly associated with risk in AAs (7p15.3 and 22q13.1). In a fixed effects meta-analysis of six regions (excluding the HLA region on chromosome 6), variation in five of the regions (2p33.3, 3p22.1, 7p15.3, 17p11.2, 22q13.1) had statistically significant associations with risk (Table 1). In one region, the index variant had the strongest association [rs4487645 at 7p15.3, (OR = 1.30, p = 8.7×10−8)]. Five of the six most significantly associated variants identified in the multiethnic analyses overlapped with biologically relevant features indicating regulatory activity based on CD20+ (B lymphocyte) cells, showing evidence of potential function; those included a missense variant in (17p11.2, rs34562254, Pro251Leu) in TNFRSF13B, which encodes a lymphocyte-specific protein in the tumor necrosis factor receptor family that interacts with the NF-kb pathway. Our study shows that these regions are important in MM risk across ethnicities and further supports the use of multiple ethnic groups in genetic studies to enhance identification of risk variants.
Table 1.Most significant associations for each region in the multiethnic meta-analysis.Individuals of European AncestryIndividuals of African AncestryMulitethnic Metar2 with IndexcCHRSNPRAaFreqbORP-valueFreqbORP-valueORP-valueP-het2rs732075G0.591.222.0×10−30.621.122.0×10−21.162.6×10−40.280.09/0.283rs73069394A0.191.243.0×10−30.621.181.5×10−21.201.3×10−50.550.77/0.963rs12637184G0.761.136.0×10−20.921.192.7×10−11.151.0×10−20.640.94/1.007rs4487645C0.671.237.0×10−40.891.485.5×10−51.308.7×10−80.07-d17rs34562254A0.121.452.4×10−50.131.212.2×10−31.312.5×10−60.120.33/0.9022rs139400T0.491.224.0×10−40.531.172.1×10−31.191.2×10−60.630.63/0.96aRisk allelebFrequency of the risk allele in European and African ancestry studiescr2 metrics based on 1000 Genomes Project AFR/EUR populationsdIndex SNP
Citation Format: Kristin A. Rand, Chi Song, Eric Dean, Daniel Serie, Karen Curtin, Dennis Hazelett, Amie E. Hwang, Xin Sheng, Alex Stram, David J. Van Den Berg, Carol Ann Huff, Leon Bernal-Mizrachi, Michael H. Tomasson, Sikander Ailawadhi, Anneclaire De Roos, Seema Singhal, Karen Pawlish, Edward Peters, Catherine Bock, David V. Conti, Graham Colditz, Todd Zimmerman, Scott Huntsman, John Graff, African Ancestry Prostate Cancer GWAS Consortium,African Ancestry Breast Cancer GWAS Consortium, Stephen J. Chanock, Michael Lieber, Jayesh Mehta, Eric A. Klein, Nalini Janakiraman, Richard K. Severson, Angela R. Brooks-Wilson, Vincent Rajkumar, Elizabeth E. Brown, Laurence Kolonel, Susan Slager, Brian E. Henderson, Graham G. Giles, John J. Spinelli, Brian Chiu, Kenneth C. Anderson, Jeffrey Zonder, Robert Z. Orlowski, Sagar Lonial, Nicola Camp, Celine Vachon, Elad Ziv, Dan O. Stram, Christopher A. Haiman, Wendy Cozen. Multiple myeloma susceptibility loci examined in African and European ancestry populations. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4629. doi:10.1158/1538-7445.AM2015-4629
Details
- Title: Subtitle
- Abstract 4629: Multiple myeloma susceptibility loci examined in African and European ancestry populations
- Creators
- Kristin A. Rand - University of Southern CaliforniaChi Song - University of Southern CaliforniaEric Dean - University of California, San FranciscoDaniel Serie - Mayo ClinicKaren Curtin - University of UtahDennis Hazelett - University of Southern CaliforniaAmie E. Hwang - University of Southern CaliforniaXin Sheng - University of Southern CaliforniaAlex Stram - University of Southern CaliforniaDavid J. Van Den Berg - University of Southern CaliforniaCarol Ann Huff - Johns Hopkins UniversityLeon Bernal-Mizrachi - Emory UniversityMichael H. Tomasson - Washington University in St. LouisSikander Ailawadhi - Mayo Clinic in ArizonaAnneclaire De Roos - Drexel UniversitySeema Singhal - Northwestern UniversityKaren Pawlish - New Jersey Department of HealthEdward Peters - Louisiana State UniversityCatherine Bock - The Barbara Ann Karmanos Cancer InstituteDavid V. Conti - University of Southern CaliforniaGraham Colditz - Washington University in St. LouisTodd Zimmerman - University of ChicagoScott Huntsman - University of California, San FranciscoJohn Graff - Rutgers, The State University of New JerseyStephen J. Chanock - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD;Michael Lieber - University of Southern CaliforniaJayesh Mehta - Northwestern UniversityEric A. KleinNalini Janakiraman - Henry Ford HospitalRichard K. Severson - The Barbara Ann Karmanos Cancer InstituteAngela R. Brooks-Wilson - BC Cancer AgencyVincent RajkumarElizabeth E. BrownLaurence Kolonel - University of Hawaii SystemSusan Slager - Mayo ClinicBrian E. Henderson - University of Southern CaliforniaGraham G. Giles - Cancer Council VictoriaJohn J. Spinelli - University of British ColumbiaBrian ChiuKenneth C. Anderson - Dana-Farber Cancer InstituteJeffrey Zonder - The Barbara Ann Karmanos Cancer InstituteRobert Z. Orlowski - The University of Texas MD Anderson Cancer CenterSagar Lonial - Emory UniversityNicola Camp - University of UtahCeline Vachon - Mayo ClinicElad Ziv - University of California, San FranciscoDan O. StramChristopher A. Haiman - University of Southern CaliforniaWendy Cozen - University of Southern CaliforniaAfrican Ancestry Prostate Cancer GWAS Consortium, African Ancestry Breast Cancer GWAS Consortium
- Resource Type
- Abstract
- Publication Details
- Cancer research (Chicago, Ill.), Vol.75(15_Supplement), pp.4629-4629
- DOI
- 10.1158/1538-7445.AM2015-4629
- ISSN
- 0008-5472
- eISSN
- 1538-7445
- Language
- English
- Date published
- 08/01/2015
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Health and Human Physiology; Internal Medicine
- Record Identifier
- 9984363432202771
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