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Two high-risk susceptibility loci at 6p25.3 and 14q32.13 for Waldenström macroglobulinemia
ML. McMaster, SI. Berndt, J. Zhang, SL. Slager, SA. Li, CM. Vajdic, KE. Smedby, H. Yan, BM. Birmann, EE. Brown, A. Smith, G. Kleinstern, MM. Fansler, C. Mayr, B. Zhu, CC. Chung, JH. Park, L. Burdette, BD. Hicks, A. Hutchinson, LR. Teras, HO....
Jazyk angličtina Země Anglie, Velká Británie
Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem
NLK
Directory of Open Access Journals
od 2015
Free Medical Journals
od 2010
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od 2010-12-01
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od 2012
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od 2010-01-01
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od 2015-01-01
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od 2015-01-01
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- MeSH
- anotace sekvence MeSH
- genetická predispozice k nemoci * MeSH
- genotypizační techniky MeSH
- HEK293 buňky MeSH
- jednonukleotidový polymorfismus genetika MeSH
- lidé MeSH
- lidské chromozomy, pár 14 genetika MeSH
- lidské chromozomy, pár 6 genetika MeSH
- mikro RNA metabolismus MeSH
- proliferace buněk MeSH
- reportérové geny MeSH
- reprodukovatelnost výsledků MeSH
- rizikové faktory MeSH
- rodina MeSH
- sekvence nukleotidů MeSH
- typy dědičnosti genetika MeSH
- Waldenströmova makroglobulinemie genetika MeSH
- zelené fluorescenční proteiny metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
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 × 10-54) and 14q32.13 (rs117410836, near TCL1; OR = 4.90, 95% CI: 3.45-6.96, P = 8.75 × 10-19). 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.
Bill Lyons Informatics Centre UCL Cancer Institute University College London London WC1E 6DD UK
Cancer Biology and Genetics Program Memorial Sloan Kettering Cancer Center New York 10065 NY USA
Cancer Epidemiology Unit University of Oxford Oxford OX3 7LF UK
Centre for Big Data Research in Health University of New South Wales Sydney 2052 NSW Australia
Department of Environmental Health Sciences Yale School of Public Health New Haven 06520 CT USA
Department of Epidemiology Brown University Providence 02903 RI USA
Department of Family Medicine and Public Health Sciences Wayne State University Detroit 48201 MI USA
Department of Health Sciences Research Mayo Clinic Rochester 55905 MN USA
Department of Health Sciences University of York York YO10 5DD UK
Department of Immunology Genetics and Pathology Uppsala University Uppsala 75105 Sweden
Department of Internal Medicine Mayo Clinic Rochester 55905 MN USA
Department of Laboratory Medicine and Pathology Mayo Clinic Rochester 55905 MN USA
Department of Medicine Memorial Sloan Kettering Cancer Center New York 10065 NY USA
Department of Pathology University of Alabama at Birmingham Birmingham 35233 AL USA
Department of Statistics Dongguk University Seoul 100 715 Republic of Korea
Division of Cancer Epidemiology and Genetics National Cancer Institute Bethesda 20892 MD USA
Division of Endocrinology Diabetes and Metabolism The Ohio State University Columbus 43210 OH USA
Division of Public Health Sciences Fred Hutchinson Cancer Research Center Seattle 98117 WA USA
Epidemiology Research Program American Cancer Society Atlanta 30303 GA USA
Genomic Epidemiology Group German Cancer Research Center Heidelberg 69120 Germany
International Agency for Research on Cancer Lyon 69372 France
School of Nursing and Human Sciences Dublin City University Dublin 9 Ireland
The Tisch Cancer Institute Icahn School of Medicine at Mount Sinai New York 10029 NY USA
Citace poskytuje Crossref.org
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