Journal article
Two high-risk susceptibility loci at 6p25.3 and 14q32.13 for Waldenström macroglobulinemia
Nature communications, Vol.9(1), 4182
10/10/2018
DOI: 10.1038/s41467-018-06541-2
PMCID: PMC6180091
PMID: 30305637
Abstract
Waldenström macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is a rare, chronic B-cell lymphoma with high heritability. We conduct a two-stage genome-wide association study of WM/LPL in 530 unrelated cases and 4362 controls of European ancestry and identify two high-risk loci associated with WM/LPL at 6p25.3 (rs116446171, near EXOC2 and IRF4; OR = 21.14, 95% CI: 14.40-31.03, P = 1.36 × 10
) and 14q32.13 (rs117410836, near TCL1; OR = 4.90, 95% CI: 3.45-6.96, P = 8.75 × 10
). Both risk alleles are observed at a low frequency among controls (~2-3%) and occur in excess in affected cases within families. In silico data suggest that rs116446171 may have functional importance, and in functional studies, we demonstrate increased reporter transcription and proliferation in cells transduced with the 6p25.3 risk allele. Although further studies are needed to fully elucidate underlying biological mechanisms, together these loci explain 4% of the familial risk and provide insights into genetic susceptibility to this malignancy.
Details
- Title: Subtitle
- Two high-risk susceptibility loci at 6p25.3 and 14q32.13 for Waldenström macroglobulinemia
- Creators
- Mary L McMaster - National Institutes of HealthBrian K Link - University of IowaSonja I Berndt - National Institutes of HealthJames R Cerhan - Mayo ClinicJianqing Zhang - University of Alabama at BirminghamSusan L Slager - Mayo ClinicShengchao Alfred Li - Leidos Biomedical Research Inc. (United States)Claire M Vajdic - UNSW SydneyKarin E Smedby - Karolinska InstitutetHuihuang Yan - Mayo ClinicBrenda M Birmann - Harvard UniversityElizabeth E Brown - University of Alabama at BirminghamAlex Smith - University of YorkGeffen Kleinstern - Mayo Clinic in FloridaMervin M Fansler - Cornell UniversityChristine Mayr - Memorial Sloan Kettering Cancer CenterBin Zhu - Leidos Biomedical Research Inc. (United States)Charles C Chung - Leidos Biomedical Research Inc. (United States)Ju-Hyun Park - Dongguk UniversityLaurie Burdette - Leidos Biomedical Research Inc. (United States)Amy Hutchinson - Leidos Biomedical Research Inc. (United States)Lauren R Teras - American Cancer SocietyHans-Olov Adami - Karolinska InstitutetPaige M Bracci - University of California, San FranciscoJames McKay - Centre international de recherche sur le cancerAlain Monnereau - Université de BordeauxRoel C H Vermeulen - University Medical Center UtrechtStephen M Ansell - Mayo ClinicAnn Maria - Memorial Sloan Kettering Cancer CenterW Ryan Diver - American Cancer SocietyMads Melbye - Stanford UniversityAkinyemi I Ojesina - University of Alabama at BirminghamPeter Kraft - Harvard UniversityPaolo Boffetta - Icahn School of Medicine at Mount SinaiJacqueline Clavel - Délégation Paris 5Edward Giovannucci - Harvard UniversityCaroline M Besson - Centre Hospitalier de VersaillesFederico Canzian - German Cancer Research CenterRuth C Travis - University of OxfordPaolo Vineis - Imperial College LondonElisabete Weiderpass - University of HelsinkiRebecca Montalvan - Westat (United States)Zhaoming Wang - National Institutes of HealthMeredith Yeager - Leidos Biomedical Research Inc. (United States)Nikolaus Becker - German Cancer Research CenterYolanda Benavente - Centro de Investigación Biomédica en Red de Epidemiología y Salud PúblicaPaul Brennan - Centre international de recherche sur le cancerLenka Foretova - Masaryk Memorial Cancer InstituteMarc Maynadie - Université de BourgogneAlexandra Nieters - University of FreiburgSilvia de Sanjose - Centro de Investigación Biomédica en Red de Epidemiología y Salud PúblicaAnthony Staines - Dublin City UniversityLucia Conde - University College LondonJacques Riby - University of Alabama at BirminghamBengt Glimelius - Uppsala UniversityHenrik Hjalgrim - Statens Serum InstitutNisha Pradhan - Memorial Sloan Kettering Cancer CenterAndrew L Feldman - Mayo ClinicAnne J Novak - Mayo ClinicCharles Lawrence - Westat (United States)Bryan A Bassig - National Institutes of HealthQing Lan - National Institutes of HealthTongzhang Zheng - Brown UniversityKari E North - University of North Carolina at Chapel HillLesley F Tinker - Fred Hutch Cancer CenterWendy Cozen - University of Southern CaliforniaRichard K Severson - Wayne State UniversityJonathan N Hofmann - National Institutes of HealthYawei Zhang - Yale UniversityRebecca D Jackson - The Ohio State UniversityLindsay M Morton - National Institutes of HealthMark P Purdue - National Institutes of HealthNilanjan Chatterjee - Johns Hopkins UniversityKenneth Offit - Memorial Sloan Kettering Cancer CenterStephen J Chanock - National Institutes of HealthNathaniel Rothman - National Institutes of HealthJoseph Vijai - Memorial Sloan Kettering Cancer CenterLynn R Goldin - National Institutes of HealthChristine F Skibola - Emory UniversityNeil E Caporaso - National Institutes of Health
- Resource Type
- Journal article
- Publication Details
- Nature communications, Vol.9(1), 4182
- DOI
- 10.1038/s41467-018-06541-2
- PMID
- 30305637
- PMCID
- PMC6180091
- NLM abbreviation
- Nat Commun
- ISSN
- 2041-1723
- eISSN
- 2041-1723
- Grant note
- UL1 TR001863 / NCATS NIH HHS R01 CA200703 / NCI NIH HHS HHSN261200800001C / CCR NIH HHS P30 CA086862 / NCI NIH HHS P50 CA097274 / NCI NIH HHS HHSN261200800001E / NCI NIH HHS
- Language
- English
- Date published
- 10/10/2018
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Epidemiology; Internal Medicine
- Record Identifier
- 9984359579202771
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