29 results on '"Goldin, Lynn"'
Search Results
2. Additional file 1: of Sex-related DNA methylation differences in B cell chronic lymphocytic leukemia
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Shuchun Lin, Liu, Yun, Goldin, Lynn, Lyu, Chen, Xiangyin Kong, Zhang, Yan, Caporaso, Neil, Xiang, Song, and Gao, Ying
- Abstract
Table S1. Samples for RNA-Seq analysis and replication of DNA methylation. Table S2. CLL subgroups of this study classified by Queiros et al. Table S3. Normal B cells subtypes samples from Kulis et al. Figure S1. Sex-related X chromosomal DMPs stratified by gene features and CpG features. Figure S2a. Thirty-six replicated autosomal DMPs. b. The 7 X chromosomal DMPs of figure 2d in EGA data. c. Genes with numbers of X chromosomal DMPs ≥ 4 in EGA data. Figure S3a. CLL sex-related DEGs. b. The 18 DNAm-DEGs and their DMPs. Figure S4a. There were 549 X chromosomal DMPs with median β 0.8 in CLL females. b. Genes with at least 3 DMPs in Figure S4a (N=43). Figure S5. MED14 hotspot detected by FEM algorithm. (DOCX 3039 kb)
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- 2019
- Full Text
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3. Additional file 2: of Prevalence of pathogenic/likely pathogenic variants in the 24 cancer genes of the ACMG Secondary Findings v2.0 list in a large cancer cohort and ethnicity-matched controls
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Kim, Jung, Luo, Wen, Mingyi Wang, Wegman-Ostrosky, Talia, Frone, Megan, Johnston, Jennifer, Nickerson, Michael, Rotunno, Melissa, Shengchao Li, Achatz, Maria, Brodie, Seth, Dean, Michael, Andrade, Kelvin, Fortes, Fernanda, Gianferante, Matthew, Payal Khincha, McMaster, Mary, McReynolds, Lisa, Pemov, Alexander, Pinheiro, Maisa, Santiago, Karina, Alter, Blanche, Caporaso, Neil, Shahinaz Gadalla, Goldin, Lynn, Greene, Mark, Loud, Jennifer, Xiaohong Yang, Freedman, Neal, Gapstur, Susan, Gaudet, Mia, Calista, Donato, Ghiorzo, Paola, Fargnoli, Maria, Nagore, Eduardo, Peris, Ketty, Puig, Susana, Landi, Maria, Belynda Hicks, Zhu, Bin, Liu, Jia, Sampson, Joshua, Chanock, Stephen, Mirabello, Lisa, Morton, Lindsay, Biesecker, Leslie, Tucker, Margaret, Savage, Sharon, Goldstein, Alisa, and Stewart, Douglas
- Abstract
Figure S1. Population stratification of cancer cases and controls. Figure S2. Principal component analysis of cancer cases and controls. Table S1. Study names and predominant cancer types in DCEG Familial Exome cohort. (PDF 449 kb)
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- 2018
- Full Text
- View/download PDF
4. Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia
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Law, Philip J, Berndt, Sonja I, Speedy, Helen E, Camp, Nicola J, Sava, Georgina P, Skibola, Christine F, Holroyd, Amy, Joseph, Vijai, Sunter, Nicola J, Nieters, Alexandra, Bea, Silvia, Monnereau, Alain, Martin-Garcia, David, Goldin, Lynn R, Clot, Guillem, Teras, Lauren R, Quintela, Inés, Birmann, Brenda M, Jayne, Sandrine, Cozen, Wendy, Majid, Aneela, Smedby, Karin E, Lan, Qing, Dearden, Claire, Brooks-Wilson, Angela R., Hall, Andrew G, Purdue, Mark P, Mainou-Fowler, Tryfonia, Vajdic, Claire M, Jackson, Graham H, Cocco, Pierluigi, Marr, Helen, Zhang, Yawei, Zheng, Tongzhang, Giles, Graham G, Lawrence, Charles, Call, Timothy G, Liebow, Mark, Melbye, Mads, Glimelius, Bengt, Mansouri, Larry, Glenn, Martha, Curtin, Karen, Diver, W Ryan, Link, Brian K, Conde, Lucia, Bracci, Paige M., Holly, Elizabeth A, Jackson, Rebecca D, Tinker, Lesley F, Benavente, Yolanda, Boffetta, Paolo, Brennan, Paul, Maynadie, Marc, McKay, James, Albanes, Demetrius, Weinstein, Stephanie, Wang, Zhaoming, Caporaso, Neil E., Morton, Lindsay M, Severson, Richard K, Riboli, Elio, Vineis, Paolo, Vermeulen, Roel C H, Southey, Melissa C, Milne, Roger L., Clavel, Jacqueline, Topka, Sabine, Spinelli, John J, Kraft, Peter, Ennas, Maria Grazia, Summerfield, Geoffrey, Ferri, Giovanni M, Harris, Robert J, Miligi, Lucia, Pettitt, Andrew R, North, Kari E, Allsup, David J, Fraumeni, Joseph F, Bailey, James R, Offit, Kenneth, Pratt, Guy, Hjalgrim, Henrik, Pepper, Christopher, Chanock, Stephen J, Fegan, Chris, Rosenquist, Richard, de Sanjose, Silvia, Carracedo, Angel, Dyer, Martin J S, Catovsky, Daniel, Campo, Elias, Cerhan, James R., Allan, James M, Rothman, Nathanial, Houlston, Richard, Slager, Susan, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Microsoft Research [Redmond], Microsoft Corporation [Redmond, Wash.], Department of Physics, Loyola College, Nungambakkam, Chennai – 600 034, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), University of Aleppo [Aleppo], Sea Mammal Research Unit [University of St Andrews] (SMRU), School of Biology [University of St Andrews], University of St Andrews [Scotland]-University of St Andrews [Scotland]-Natural Environment Research Council (NERC), Department of Chemical Engineering, Imperial College London, De la Molécule aux Nanos-objets : Réactivité, Interactions et Spectroscopies (MONARIS), Institut de Chimie du CNRS (INC)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), The Cancer Council Victoria, University of Oulu, Uppsala Universitet [Uppsala], Université Paris Nanterre (UPN), University of Iowa [Iowa City], Registre des hémopathies malignes de Côte d'Or, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), B.B. Brodie Department of Neuroscience, Pennsylvania State University (Penn State), Penn State System, University of Newcastle [Australia] (UoN), Astrophysique Interprétation Modélisation (AIM (UMR_7158 / UMR_E_9005 / UM_112)), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7), Department of Haematology, School of Medicine, Cardiff University, CIBER de Enfermedades Raras (CIBERER), University of Leeds, Haemato-oncology, Institute of cancer research, Mayo Clinic [Rochester], Northern Institute for Cancer Research [Newcastle] (NICR), Newcastle University [Newcastle], Institute of Cancer Research, Belmont, Sutton, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Sea Mammal Research Unit, Scottish Oceans Institute, University of St Andrews [Scotland], Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), University of Cardiff, Équipe Instrumentation embarquée et systèmes de surveillance intelligents (LAAS-S4M), Laboratoire d'analyse et d'architecture des systèmes (LAAS), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse 1 Capitole (UT1)-Université Toulouse - Jean Jaurès (UT2J)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse 1 Capitole (UT1)-Université Toulouse - Jean Jaurès (UT2J), University of Newcastle [Callaghan, Australia] (UoN), Astrophysique Interprétation Modélisation (AIM (UMR7158 / UMR_E_9005 / UM_112)), LS IRAS EEPI GRA (Gezh.risico-analyse), dIRAS RA-2, Université Toulouse 1 Capitole (UT1)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse 1 Capitole (UT1)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), and Université Fédérale Toulouse Midi-Pyrénées
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Adult ,Male ,RM ,Cancer och onkologi ,B-Lymphocytes ,[SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT] ,Science ,Chromosome Mapping ,Middle Aged ,Leukemia, Lymphocytic, Chronic, B-Cell ,Polymorphism, Single Nucleotide ,Article ,Young Adult ,Cancer and Oncology ,Case-Control Studies ,Antibody Formation ,Chromosomes, Human ,Humans ,Female ,Genetic Predisposition to Disease ,RC ,Genome-Wide Association Study - Abstract
Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10−13), 1q42.13 (rs41271473, P=1.06 × 10−10), 4q24 (rs71597109, P=1.37 × 10−10), 4q35.1 (rs57214277, P=3.69 × 10−8), 6p21.31 (rs3800461, P=1.97 × 10−8), 11q23.2 (rs61904987, P=2.64 × 10−11), 18q21.1 (rs1036935, P=3.27 × 10−8), 19p13.3 (rs7254272, P=4.67 × 10−8) and 22q13.33 (rs140522, P=2.70 × 10−9). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response., Chronic lymphocytic leukaemia has a hereditary component, much of which remains to be identified. Here, the authors perform a genome-wide association study and find new risk loci for the disease, which are associated with genes involved in immune function.
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- 2017
- Full Text
- View/download PDF
5. Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia
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Law, Philip J, Berndt, Sonja I., Speedy, Helen E, Camp, Nicola J, Sava, Georgina P, Skibola, Christine F., Holroyd, Amy, Joseph, Vijai, Sunter, Nicola J, Nieters, Alexandra, Bea, Silvia, Monnereau, Alain, Martin-Garcia, David, Goldin, Lynn R, Clot, Guillem, Teras, Lauren R., Quintela, Inés, Birmann, Brenda M., Jayne, Sandrine, Cozen, Wendy, Majid, Aneela, Smedby, Karin E, Lan, Qing, Dearden, Claire, Brooks-Wilson, Angela R., Hall, Andrew G, Purdue, Mark P., Mainou-Fowler, Tryfonia, Vajdic, Claire M., Jackson, Graham H, Cocco, Pierluigi, Marr, Helen, Zhang, Yawei, Zheng, Tongzhang, Giles, Graham G., Lawrence, Charles, Call, Timothy G., Liebow, Mark, Melbye, Mads, Glimelius, Bengt, Mansouri, Larry, Glenn, Martha, Curtin, Karen, Diver, W. Ryan, Link, Brian K., Conde, Lucia, Bracci, Paige M., Holly, Elizabeth A., Jackson, Rebecca D., Tinker, Lesley F., Benavente, Yolanda, Boffetta, Paolo, Brennan, Paul, Maynadie, Marc, McKay, James, Albanes, Demetrius, Weinstein, Stephanie, Wang, Zhaoming, Caporaso, Neil E, Morton, Lindsay M., Severson, Richard K., Riboli, Elio, Vineis, Paolo, Vermeulen, Roel C H, Southey, Melissa C., Milne, Roger L, Clavel, Jacqueline, Topka, Sabine, Spinelli, John, Kraft, Peter, Ennas, Maria Grazia, Summerfield, Geoffrey, Ferri, Giovanni M, Harris, Robert J, Miligi, Lucia, Pettitt, Andrew R, North, Kari E., Allsup, David J, Fraumeni, Joseph F., Bailey, James R, Offit, Kenneth, Pratt, Guy, Hjalgrim, Henrik, Pepper, Chris, Chanock, Stephen J., Fegan, Chris, Rosenquist, Richard, De Sanjose, Silvia, Carracedo, Angel, Dyer, Martin J S, Catovsky, Daniel, Campo, Elias, Cerhan, James R., Allan, James M, Rothman, Nathanial, Houlston, Richard S, Slager, Susan L., LS IRAS EEPI GRA (Gezh.risico-analyse), and dIRAS RA-2
- Abstract
Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10-13), 1q42.13 (rs41271473, P=1.06 × 10-10), 4q24 (rs71597109, P=1.37 × 10-10), 4q35.1 (rs57214277, P=3.69 × 10-8), 6p21.31 (rs3800461, P=1.97 × 10-8), 11q23.2 (rs61904987, P=2.64 × 10-11), 18q21.1 (rs1036935, P=3.27 × 10-8), 19p13.3 (rs7254272, P=4.67 × 10-8) and 22q13.33 (rs140522, P=2.70 × 10-9). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response.
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- 2017
6. Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia
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Law, Philip J, Berndt, Sonja I, Speedy, Helen E, Camp, Nicola J, Sava, Georgina P, Skibola, Christine F, Holroyd, Amy, Vijai, Joseph, Sunter, Nicola J, Nieters, Alexandra, Bea, Silvia, Pettitt, AR, Monnereau, Alain, Martin-Garcia, David, Goldin, Lynn R, Clot, Guillem, Teras, Lauren R, Quintela, Inés, Birmann, Brenda M, Jayne, Sandrine J, Cozen, Wendy, Majid, Aneela, Smedby, Karin E, Lan, Qing, Dearden, Claire, Brooks-Wilson, Angela R, Hall, Andrew G, Purdue, Mark P, Mainou-Fowler, Tryfonia, Vajdic, Claire M, Jackson, Graham H, Cocco, Pierluigi, Marr, Helen, Zhang, Yawei, Zheng, Tongzhang, Giles, Graham G, Lawrence, Charles, Call, Timothy G, Liebow, Mark, Melbye, Mads, Glimelius, Bengt, Mansouri, Larry, Glenn, Martha, Curtin, Karen, Diver, W Ryan, Link, Brian K, Conde, Lucia, Bracci, Paige M, Holly, Elizabeth A, Jackson, Rebecca D, Tinker, Lesley F, Benavente, Yolanda, Boffetta, Paolo, Brennan, Paul, Maynadie, Marc, Mckay, James, Albanes, Demetrius, Weinstein, Stephanie, Wang, Zhaoming, Caporaso, Neil E, Morton, Lindsay M, Severson, Richard K, Riboli, Elio, Vineis, Paolo, Vermeulen, Roel CH, Southey, Melissa C, Milne, Roger L, Clavel, Jacqueline, Topka, Sabine, Spinelli, John J, Kraft, Peter, Ennas, Maria Grazia, Summerfield, Geoffrey, Ferri, Giovanni M, Harris, Robert J, Miligi, Lucia, Pettitt, Andrew R, North, Kari E, Allsup, David J, Fraumeni, Joseph F, Bailey, James R, Offit, Kenneth, Pratt, Guy, Hjalgrim, Henrik, Pepper, Chris, Chanock, Stephen J, Fegan, Chris, Rosenquist, Richard, Sanjose, Silvia de, Carracedo, Angel, Dyer, Martin JS, Catovsky, Daniel, Campo, Elias, Cerhan, James R, Allan, James M, Rothman, Nathanial, Houlston, Richard, Slager, Susan, Law, P.J., Berndt, S.I., Speedy, H.E., Camp, N.J., Sava, G.P., Skibola, C.F., Holroyd, A., Joseph, V., Sunter, N.J., Nieters, A., Bea, S., Monnereau, A., Martin-Garcia, D., Goldin, L.R., Clot, G., Teras, L.R., Quintela, I., Birmann, B.M., Jayne, S., Cozen, W., Majid, A., Smedby, K.E., Lan, Q., Dearden, C., Brooks-Wilson, A.R., Hall, A.G., Purdue, M.P., Mainou-Fowler, T., Vajdic, C.M., Jackson, G.H., Cocco, P., Marr, H., Zhang, Y., Zheng, T., Giles, G.G., Lawrence, C., Call, T.G., Liebow, M., Melbye, M., Glimelius, B., Mansouri, L., Glenn, M., Curtin, K., Diver, W.R., Link, B.K., Conde, L., Bracci, P.M., Holly, E.A., Jackson, R.D., Tinker, L.F., Benavente, Y., Boffetta, P., Brennan, P., Maynadie, M., McKay, J., Albanes, D., Weinstein, S., Wang, Z., Caporaso, N.E., Morton, L.M., Severson, R.K., Riboli, E., Vineis, P., Vermeulen, R.C.H., Southey, M.C., Milne, R.L., Clavel, J., Topka, S., Spinelli, J.J., Kraft, P., Ennas, M.G., Summerfield, G., Ferri, G.M., Harris, R.J., Miligi, L., Pettitt, A.R., North, K.E., Allsup, D.J., Fraumeni, J.F., Jr., Bailey, J.R., Offit, K., Pratt, G., Hjalgrim, H., Pepper, C., Chanock, S.J., Fegan, C., Rosenquist, R., De Sanjose, S., Carracedo, A., Dyer, M.J.S., Catovsky, D., Campo, E., Cerhan, J.R., Allan, J.M., Rothman, N., Houlston, R., and Slager, S.
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Lymphocytic leukaemia - Abstract
Several chronic 14175 lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10-13), 1q42.13 (rs41271473, P=1.06 × 10-10), 4q24 (rs71597109, P=1.37 × 10 -10), 4q35.1 (rs57214277, P=3.69 × 10-8), 6p21.31 (rs3800461, P=1.97 × 10-8), 11q23.2 (rs61904987, P=2.64 × 10-11), 18q21.1 (rs1036935, P=3.27 × 10-8), 19p13.3 (rs7254272, P=4.67 × 10-8) and 22q13.33 (rs140522, P=2.70 × 10-9). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response.
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- 2017
7. Whole exome sequencing reveals a C-terminal germline variant in CEBPA-associated acute myeloid leukemia: 45-year follow up of a large family
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Pathak, Anand, Seipel, Katja, Pemov, Alexander, Dewan, Ramita, Brown, Christina, Ravichandran, Sarangan, Luke, Brian T, Malasky, Michael, Suman, Shalabh, Yeager, Meredith, NCI DCEG Cancer Genomics Research Laboratory, NCI DCEG Cancer Sequencing Working Group, Gatti, Richard A, Caporaso, Neil E, Mulvihill, John J, Goldin, Lynn R, Pabst, Thomas, McMaster, Mary L, and Stewart, Douglas R
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Adult ,Male ,Myeloid ,Genotype ,Adolescent ,Protein Conformation ,NCI DCEG Cancer Sequencing Working Group ,Immunology ,Acute ,Cardiorespiratory Medicine and Haematology ,Young Adult ,Rare Diseases ,Models ,Clinical Research ,CCAAT-Enhancer-Binding Protein-alpha ,Genetics ,Humans ,2.1 Biological and endogenous factors ,Family ,Protein Interaction Domains and Motifs ,Exome ,Aetiology ,Child ,Preschool ,Germ-Line Mutation ,Alleles ,Cancer ,Leukemic ,Pediatric ,Leukemia ,Human Genome ,Molecular ,High-Throughput Nucleotide Sequencing ,Hematology ,Middle Aged ,NCI DCEG Cancer Genomics Research Laboratory ,Pedigree ,Gene Expression Regulation ,Female ,Protein Multimerization ,Follow-Up Studies - Abstract
Familial acute myeloid leukemia is rare and linked to germline mutations in RUNX1, GATA2 or CCAAT/enhancer binding protein-α (CEBPA). We re-evaluated a large family with acute myeloid leukemia originally seen at NIH in 1969. We used whole exome sequencing to study this family, and conducted in silico bioinformatics analysis, protein structural modeling and laboratory experiments to assess the impact of the identified CEBPA Q311P mutation. Unlike most previously identified germline mutations in CEBPA, which were N-terminal frameshift mutations, we identified a novel Q311P variant that was located in the C-terminal bZip domain of C/EBPα. Protein structural modeling suggested that the Q311P mutation alters the ability of the CEBPA dimer to bind DNA. Electrophoretic mobility shift assays showed that the Q311P mu-tant had attenuated binding to DNA, as predicted by the protein modeling. Consistent with these findings, we found that the Q311P mutation has reduced transactivation, consistent with a loss-of-function mutation. From 45 years of follow up, we observed incomplete penetrance (46%) of CEBPA Q311P. This study of a large multi-generational pedigree reveals that a germline mutation in the C-terminal bZip domain can alter the ability of C/EBP-α to bind DNA and reduces transactivation, leading to acute myeloid leukemia.
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- 2016
8. Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome
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Machiela, Mitchell J, Zhou, Weiyin, Karlins, Eric, Sampson, Joshua N, Freedman, Neal D, Yang, Qi, Hicks, Belynda, Dagnall, Casey, Hautman, Christopher, Jacobs, Kevin B, Abnet, Christian C, Aldrich, Melinda C, Amos, Christopher, Amundadottir, Laufey T, Arslan, Alan A, Beane-Freeman, Laura E, Berndt, Sonja I, Black, Amanda, Blot, William J, Bock, Cathryn H, Bracci, Paige M, Brinton, Louise A, Bueno-de-Mesquita, H Bas, Burdett, Laurie, Buring, Julie E, Butler, Mary A, Canzian, Federico, Carreon, Tania, Chaffee, Kari G, Chang, I-Shou, Chatterjee, Nilanjan, Chen, Chu, Chen, Constance, Chen, Kexin, Chung, Charles C, Cook, Linda S, Bou, Marta Crous, Cullen, Michael, Davis, Faith G, De Vivo, Immaculata, Ding, Ti, Doherty, Jennifer, Duell, Eric J, Epstein, Caroline G, Fan, Jin-Hu, Figueroa, Jonine D, Fraumeni, Joseph F, Friedenreich, Christine M, Fuchs, Charles S, Gallinger, Steven, Gao, Yu-Tang, Gapstur, Susan M, Garcia-Closas, Montserrat, Gaudet, Mia M, Gaziano, J Michael, Giles, Graham G, Gillanders, Elizabeth M, Giovannucci, Edward L, Goldin, Lynn, Goldstein, Alisa M, Haiman, Christopher A, Hallmans, Goran, Hankinson, Susan E, Harris, Curtis C, Henriksson, Roger, Holly, Elizabeth A, Hong, Yun-Chul, Hoover, Robert N, Hsiung, Chao A, Hu, Nan, Hu, Wei, Hunter, David J, Hutchinson, Amy, Jenab, Mazda, Johansen, Christoffer, Khaw, Kay-Tee, Kim, Hee Nam, Kim, Yeul Hong, Kim, Young Tae, Klein, Alison P, Klein, Robert, Koh, Woon-Puay, Kolonel, Laurence N, Kooperberg, Charles, Kraft, Peter, Krogh, Vittorio, Kurtz, Robert C, LaCroix, Andrea, Lan, Qing, Landi, Maria Teresa, Le Marchand, Loic, Li, Donghui, Liang, Xiaolin, Liao, Linda M, Lin, Dongxin, Liu, Jianjun, Lissowska, Jolanta, Lu, Lingeng, Magliocco, Anthony M, and Malats, Nuria
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- 2016
9. Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia
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Berndt, Sonja I, Skibola, Christine F, Joseph, Vijai, Camp, Nicola J, Nieters, Alexandra, Wang, Zhaoming, Cozen, Wendy, Monnereau, Alain, Wang, Sophia S, Kelly, Rachel S, Lan, Qing, Teras, Lauren R, Chatterjee, Nilanjan, Chung, Charles C, Yeager, Meredith, Brooks-Wilson, Angela R, Hartge, Patricia, Purdue, Mark P, Birmann, Brenda M, Armstrong, Bruce K, Cocco, Pierluigi, Zhang, Yawei, Severi, Gianluca, Zeleniuch-Jacquotte, Anne, Lawrence, Charles, Burdette, Laurie, Yuenger, Jeffrey, Hutchinson, Amy, Jacobs, Kevin B, Call, Timothy G, Shanafelt, Tait D, Novak, Anne J, Kay, Neil E, Liebow, Mark, Wang, Alice H, Smedby, Karin E, Adami, Hans-Olov, Melbye, Mads, Glimelius, Bengt, Chang, Ellen T, Glenn, Martha, Curtin, Karen, Cannon-Albright, Lisa A, Jones, Brandt, Diver, W Ryan, Link, Brian K, Weiner, George J, Conde, Lucia, Bracci, Paige M, Riby, Jacques, Holly, Elizabeth A, Smith, Martyn T, Jackson, Rebecca D, Tinker, Lesley F, Benavente, Yolanda, Becker, Nikolaus, Boffetta, Paolo, Brennan, Paul, Foretova, Lenka, Maynadie, Marc, McKay, James, Staines, Anthony, Rabe, Kari G, Achenbach, Sara J, Vachon, Celine M, Goldin, Lynn R, Strom, Sara S, Lanasa, Mark C, Spector, Logan G, Leis, Jose F, Cunningham, Julie M, Weinberg, J Brice, Morrison, Vicki A, Caporaso, Neil E, Norman, Aaron D, Linet, Martha S, De Roos, Anneclaire J, Morton, Lindsay M, Severson, Richard K, Riboli, Elio, Vineis, Paolo, Kaaks, Rudolph, Trichopoulos, Dimitrios, Masala, Giovanna, Weiderpass, Elisabete, Chirlaque, María-Dolores, Vermeulen, Roel CH, Travis, Ruth C, Giles, Graham G, Albanes, Demetrius, Virtamo, Jarmo, Weinstein, Stephanie, Clavel, Jacqueline, Zheng, Tongzhang, Holford, Theodore R, Offit, Kenneth, Zelenetz, Andrew, Klein, Robert J, Spinelli, John J, and Bertrand, Kimberly A
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Risk ,Leukemia ,B-Cell ,Single Nucleotide ,Biological Sciences ,Medical and Health Sciences ,Chromosomes ,Recombination ,Linkage Disequilibrium ,Lymphocytic ,Genetic ,Genetic Loci ,Case-Control Studies ,Pair 2 ,Humans ,Genetic Predisposition to Disease ,Polymorphism ,Chronic ,Human ,Genome-Wide Association Study ,Developmental Biology - Abstract
Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P=1.22×10(-14)), 18q21.33 (BCL2, P=7.76×10(-11)), 11p15.5 (C11orf21, P=2.15×10(-10)), 4q25 (LEF1, P=4.24×10(-10)), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P=2.50×10(-9)), 9p21.3 (CDKN2B-AS1, P=1.27×10(-8)), 18q21.32 (PMAIP1, P=2.51×10(-8)), 15q15.1 (BMF, P=2.71×10(-10)) and 2p22.2 (QPCT, P=1.68×10(-8)), as well as an independent signal at an established locus (2q13, ACOXL, P=2.08×10(-18)). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P=5.40×10(-8)) and 5p15.33 (TERT, P=1.92×10(-7)). Although further studies are required, the proximity of several of these loci to genes involved in apoptosis suggests a plausible underlying biological mechanism.
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- 2013
10. Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia
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Berndt, Sonja I, Skibola, Christine F, Joseph, Vijai, Camp, Nicola J, Nieters, Alexandra, Wang, Zhaoming, Cozen, Wendy, Monnereau, Alain, Wang, Sophia S, Kelly, Rachel S, Lan, Qing, Teras, Lauren R, Chatterjee, Nilanjan, Chung, Charles C, Yeager, Meredith, Brooks-Wilson, Angela R, Hartge, Patricia, Purdue, Mark P, Birmann, Brenda M, Armstrong, Bruce K, Cocco, Pierluigi, Zhang, Yawei, Severi, Gianluca, Zeleniuch-Jacquotte, Anne, Lawrence, Charles, Burdette, Laurie, Yuenger, Jeffrey, Hutchinson, Amy, Jacobs, Kevin B, Call, Timothy G, Shanafelt, Tait D, Novak, Anne J, Kay, Neil E, Liebow, Mark, Wang, Alice H, Smedby, Karin E, Adami, Hans-Olov, Melbye, Mads, Glimelius, Bengt, Chang, Ellen T, Glenn, Martha, Curtin, Karen, Cannon-Albright, Lisa A, Jones, Brandt, Diver, W Ryan, Link, Brian K, Weiner, George J, Conde, Lucia, Bracci, Paige M, Riby, Jacques, Holly, Elizabeth A, Smith, Martyn T, Jackson, Rebecca D, Tinker, Lesley F, Benavente, Yolanda, Becker, Nikolaus, Boffetta, Paolo, Brennan, Paul, Foretova, Lenka, Maynadie, Marc, McKay, James, Staines, Anthony, Rabe, Kari G, Achenbach, Sara J, Vachon, Celine M, Goldin, Lynn R, Strom, Sara S, Lanasa, Mark C, Spector, Logan G, Leis, Jose F, Cunningham, Julie M, Weinberg, J Brice, Morrison, Vicki A, Caporaso, Neil E, Norman, Aaron D, Linet, Martha S, De Roos, Anneclaire J, Morton, Lindsay M, Severson, Richard K, Riboli, Elio, Vineis, Paolo, Kaaks, Rudolph, Trichopoulos, Dimitrios, Masala, Giovanna, Weiderpass, Elisabete, Chirlaque, María-Dolores, Vermeulen, Roel CH, Travis, Ruth C, Giles, Graham G, Albanes, Demetrius, Virtamo, Jarmo, Weinstein, Stephanie, Clavel, Jacqueline, Zheng, Tongzhang, Holford, Theodore R, Offit, Kenneth, Zelenetz, Andrew, Klein, Robert J, Spinelli, John J, and Bertrand, Kimberly A
- Subjects
Risk ,Leukemia ,B-Cell ,Single Nucleotide ,Biological Sciences ,Medical and Health Sciences ,Chromosomes ,Recombination ,Linkage Disequilibrium ,Lymphocytic ,Genetic ,Genetic Loci ,Case-Control Studies ,Pair 2 ,Humans ,Genetic Predisposition to Disease ,Polymorphism ,Chronic ,Human ,Genome-Wide Association Study ,Cancer ,Developmental Biology - Abstract
Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P=1.22×10(-14)), 18q21.33 (BCL2, P=7.76×10(-11)), 11p15.5 (C11orf21, P=2.15×10(-10)), 4q25 (LEF1, P=4.24×10(-10)), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P=2.50×10(-9)), 9p21.3 (CDKN2B-AS1, P=1.27×10(-8)), 18q21.32 (PMAIP1, P=2.51×10(-8)), 15q15.1 (BMF, P=2.71×10(-10)) and 2p22.2 (QPCT, P=1.68×10(-8)), as well as an independent signal at an established locus (2q13, ACOXL, P=2.08×10(-18)). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P=5.40×10(-8)) and 5p15.33 (TERT, P=1.92×10(-7)). Although further studies are required, the proximity of several of these loci to genes involved in apoptosis suggests a plausible underlying biological mechanism.
- Published
- 2013
11. Detectable clonal mosaicism and its relationship to aging and cancer
- Author
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Jacobs, Kevin B. Yeager, Meredith Zhou, Weiyin Wacholder, Sholom Wang, Zhaoming Rodriguez-Santiago, Benjamin and Hutchinson, Amy Deng, Xiang Liu, Chenwei Horner, Marie-Josephe Cullen, Michael Epstein, Caroline G. Burdett, Laurie Dean, Michael C. Chatterjee, Nilanjan Sampson, Joshua and Chung, Charles C. Kovaks, Joseph Gapstur, Susan M. and Stevens, Victoria L. Teras, Lauren T. Gaudet, Mia M. and Albanes, Demetrius Weinstein, Stephanie J. Virtamo, Jarmo and Taylor, Philip R. Freedman, Neal D. Abnet, Christian C. and Goldstein, Alisa M. Hu, Nan Yu, Kai Yuan, Jian-Min Liao, Linda Ding, Ti Qiao, You-Lin Gao, Yu-Tang Koh, Woon-Puay and Xiang, Yong-Bing Tang, Ze-Zhong Fan, Jin-Hu Aldrich, Melinda C. Amos, Christopher Blot, William J. Bock, Cathryn H. Gillanders, Elizabeth M. Harris, Curtis C. Haiman, Christopher A. Henderson, Brian E. Kolonel, Laurence N. Le Marchand, Loic McNeill, Lorna H. Rybicki, Benjamin A. and Schwartz, Ann G. Signorello, Lisa B. Spitz, Margaret R. and Wiencke, John K. Wrensch, Margaret Wu, Xifeng Zanetti, Krista A. Ziegler, Regina G. Figueroa, Jonine D. and Garcia-Closas, Montserrat Malats, Nuria Marenne, Gaelle and Prokunina-Olsson, Ludmila Baris, Dalsu Schwenn, Molly and Johnson, Alison Landi, Maria Teresa Goldin, Lynn Consonni, Dario Bertazzi, Pier Alberto Rotunno, Melissa Rajaraman, Preetha Andersson, Ulrika Freeman, Laura E. Beane Berg, Christine D. Buring, Julie E. Butler, Mary A. Carreon, Tania and Feychting, Maria Ahlbom, Anders Gaziano, J. Michael and Giles, Graham G. Hallmans, Goran Hankinson, Susan E. Hartge, Patricia Henriksson, Roger Inskip, Peter D. Johansen, Christoffer Landgren, Annelie McKean-Cowdin, Roberta and Michaud, Dominique S. Melin, Beatrice S. Peters, Ulrike and Ruder, Avima M. Sesso, Howard D. Severi, Gianluca Shu, Xiao-Ou Visvanathan, Kala White, Emily Wolk, Alicja and Zeleniuch-Jacquotte, Anne Zheng, Wei Silverman, Debra T. and Kogevinas, Manolis Gonzalez, Juan R. Villa, Olaya Li, Donghui Duell, Eric J. Risch, Harvey A. Olson, Sara H. and Kooperberg, Charles Wolpin, Brian M. Jiao, Li Hassan, Manal and Wheeler, William Arslan, Alan A. Bueno-de-Mesquita, H. Bas and Fuchs, Charles S. Gallinger, Steven Gross, Myron D. and Holly, Elizabeth A. Klein, Alison P. LaCroix, Andrea and Mandelson, Margaret T. Petersen, Gloria Boutron-Ruault, Marie-Christine Bracci, Paige M. Canzian, Federico Chang, Kenneth Cotterchio, Michelle Giovannucci, Edward L. Goggins, Michael Bolton, Judith A. Hoffman Jenab, Mazda Khaw, Kay-Tee and Krogh, Vittorio Kurtz, Robert C. McWilliams, Robert R. and Mendelsohn, Julie B. Rabe, Kari G. Riboli, Elio Tjonneland, Anne Tobias, Geoffrey S. Trichopoulos, Dimitrios Elena, Joanne W. Yu, Herbert Amundadottir, Laufey and Stolzenberg-Solomon, Rachael Z. Kraft, Peter Schumacher, Fredrick Stram, Daniel Savage, Sharon A. Mirabello, Lisa and Andrulis, Irene L. Wunder, Jay S. Patino Garcia, Ana and Sierrasesumaga, Luis Barkauskas, Donald A. Gorlick, Richard G. and Purdue, Mark Chow, Wong-Ho Moore, Lee E. Schwartz, Kendra L. Davis, Faith G. Hsing, Ann W. Berndt, Sonja I. and Black, Amanda Wentzensen, Nicolas Brinton, Louise A. and Lissowska, Jolanta Peplonska, Beata McGlynn, Katherine A. and Cook, Michael B. Graubard, Barry I. Kratz, Christian P. and Greene, Mark H. Erickson, Ralph L. Hunter, David J. Thomas, Gilles Hoover, Robert N. Real, Francisco X. Fraumeni, Jr., Joseph F. Caporaso, Neil E. Tucker, Margaret Rothman, Nathaniel Perez-Jurado, Luis A. Chanock, Stephen J.
- Abstract
In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of > 2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 x 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 x 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.
- Published
- 2012
12. Common Occurrence of Monoclonal B-cell Lymphocytosis Among Members of High-Risk CLL Families
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Goldin, Lynn R., Lanasa, Mark C., Slager, Susan L., Cerhan, James R., Vachon, Celine M., Strom, Sara S., Camp, Nicola J., Spector, Logan G., Leis, Jose F., Morrison, Vicki A., Glenn, Martha, Rabe, Kari G., Achenbach, Sara J., Algood, Sallie D., Abbasi, Fatima, Fontaine, Laura, Yau, Michelle, Rassenti, Laura Z., Kay, Neil E., Call, Timothy G., Hanson, Curtis A., Weinberg, J. Brice, Marti, Gerald E., and Caporaso, Neil E.
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Adult ,Aged, 80 and over ,Male ,B-Lymphocytes ,chemical and pharmacologic phenomena ,Lymphocytosis ,Middle Aged ,bacterial infections and mycoses ,Flow Cytometry ,Leukemia, Lymphocytic, Chronic, B-Cell ,Article ,United States ,Immunophenotyping ,Age Distribution ,hemic and lymphatic diseases ,Humans ,Female ,Sex Distribution ,Aged - Abstract
Monoclonal B-cell lymphocytosis (MBL) is an asymptomatic haematological condition characterized by low absolute levels of B-cell clones with a surface immunophenotype similar to that of chronic lymphocytic leukaemia (CLL). In the general population, MBL increases with age with a prevalence of 5-9% in individuals over age 60 years. It has been reported to be higher among first-degree relatives from CLL families. We report results of multi-parameter flow cytometry among 505 first-degree relatives with no personal history of lymphoproliferative disease from 140 families having at least two cases of CLL. Seventeen percent of relatives had MBL. Age was the most important determinant where the probability for developing MBL by age 90 years was 61%. MBL clustered in certain families but clustering was independent of the number of known CLL cases in a family. As is the case with CLL, males had a significantly higher risk for MBL than did females (P = 0·04). MBL patients had significantly higher mean absolute lymphocyte counts (2·4 × 10(9) /l) and B-cell counts (0·53 × 10(9) /l) than those with a normal B-cell immuno-phenotype. Our findings show that MBL occurs at a very high rate in high risk CLL families. Both the age and gender distribution of MBL are parallel to CLL, implying a shared inherited risk.
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- 2010
13. Genome-wide association study of follicular lymphoma identifies a risk locus at 6p21.32
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Conde, Lucia, Halperin, Eran, Akers, Nicholas K, Brown, Kevin M, Smedby, Karin E, Rothman, Nathaniel, Nieters, Alexandra, Slager, Susan L, Brooks-Wilson, Angela, Agana, Luz, Riby, Jacques, Liu, Jianjun, Adami, Hans-Olov, Darabi, Hatef, Hjalgrim, Henrik, Low, Hui-Qi, Humphreys, Keith, Melbye, Mads, Chang, Ellen T, Glimelius, Bengt, Cozen, Wendy, Davis, Scott, Hartge, Patricia, Morton, Lindsay M, Schenk, Maryjean, Wang, Sophia S, Armstrong, Bruce, Kricker, Anne, Milliken, Sam, Purdue, Mark P, Vajdic, Claire M, Boyle, Peter, Lan, Qing, Zahm, Shelia H, Zhang, Yawei, Zheng, Tongzhang, Becker, Nikolaus, Benavente, Yolanda, Boffetta, Paolo, Brennan, Paul, Butterbach, Katja, Cocco, Pierluigi, Foretova, Lenka, Maynadié, Marc, de Sanjosé, Silvia, Staines, Anthony, Spinelli, John J, Achenbach, Sara J, Call, Timothy G, Camp, Nicola J, Glenn, Martha, Caporaso, Neil E, Cerhan, James R, Cunningham, Julie M, Goldin, Lynn R, Hanson, Curtis A, Kay, Neil E, Lanasa, Mark C, Leis, Jose F, Marti, Gerald E, Rabe, Kari G, Rassenti, Laura Z, Spector, Logan G, Strom, Sara S, Vachon, Celine M, Weinberg, J Brice, Holly, Elizabeth A, Chanock, Stephen, Smith, Martyn T, Bracci, Paige M, and Skibola, Christine F
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Leukemia ,Lymphoma ,Prevention ,Human Genome ,Follicular ,B-Cell ,Non-Hodgkin ,Genetic Variation ,Hematology ,Biological Sciences ,Medical and Health Sciences ,Lymphocytic ,Major Histocompatibility Complex ,Rare Diseases ,Risk Factors ,Genetics ,Humans ,2.1 Biological and endogenous factors ,Disease Susceptibility ,Chronic ,Aetiology ,Genome-Wide Association Study ,Cancer ,Developmental Biology - Abstract
To identify susceptibility loci for non-Hodgkin lymphoma subtypes, we conducted a three-stage genome-wide association study. We identified two variants associated with follicular lymphoma at 6p21.32 (rs10484561, combined P = 1.12 x 10(-29) and rs7755224, combined P = 2.00 x 10(-19); r(2) = 1.0), supporting the idea that major histocompatibility complex genetic variation influences follicular lymphoma susceptibility. We also found confirmatory evidence of a previously reported association between chronic lymphocytic leukemia/small lymphocytic lymphoma and rs735665 (combined P = 4.24 x 10(-9)).
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- 2010
14. Genome-wide association study of follicular lymphoma identifies a risk locus at 6p21.32
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Conde, Lucia, Halperin, Eran, Akers, Nicholas K, Brown, Kevin M, Smedby, Karin E, Rothman, Nathaniel, Nieters, Alexandra, Slager, Susan L, Brooks-Wilson, Angela, Agana, Luz, Riby, Jacques, Liu, Jianjun, Adami, Hans-Olov, Darabi, Hatef, Hjalgrim, Henrik, Low, Hui-Qi, Humphreys, Keith, Melbye, Mads, Chang, Ellen T, Glimelius, Bengt, Cozen, Wendy, Davis, Scott, Hartge, Patricia, Morton, Lindsay M, Schenk, Maryjean, Wang, Sophia S, Armstrong, Bruce, Kricker, Anne, Milliken, Sam, Purdue, Mark P, Vajdic, Claire M, Boyle, Peter, Lan, Qing, Zahm, Shelia H, Zhang, Yawei, Zheng, Tongzhang, Becker, Nikolaus, Benavente, Yolanda, Boffetta, Paolo, Brennan, Paul, Butterbach, Katja, Cocco, Pierluigi, Foretova, Lenka, Maynadié, Marc, de Sanjosé, Silvia, Staines, Anthony, Spinelli, John J, Achenbach, Sara J, Call, Timothy G, Camp, Nicola J, Glenn, Martha, Caporaso, Neil E, Cerhan, James R, Cunningham, Julie M, Goldin, Lynn R, Hanson, Curtis A, Kay, Neil E, Lanasa, Mark C, Leis, Jose F, Marti, Gerald E, Rabe, Kari G, Rassenti, Laura Z, Spector, Logan G, Strom, Sara S, Vachon, Celine M, Weinberg, J Brice, Holly, Elizabeth A, Chanock, Stephen, Smith, Martyn T, Bracci, Paige M, and Skibola, Christine F
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Leukemia ,Lymphoma ,Follicular ,B-Cell ,Non-Hodgkin ,Genetic Variation ,Biological Sciences ,Medical and Health Sciences ,Lymphocytic ,Major Histocompatibility Complex ,Risk Factors ,hemic and lymphatic diseases ,Humans ,Disease Susceptibility ,Chronic ,Genome-Wide Association Study ,Developmental Biology - Abstract
To identify susceptibility loci for non-Hodgkin lymphoma subtypes, we conducted a three-stage genome-wide association study. We identified two variants associated with follicular lymphoma at 6p21.32 (rs10484561, combined P = 1.12 x 10(-29) and rs7755224, combined P = 2.00 x 10(-19); r(2) = 1.0), supporting the idea that major histocompatibility complex genetic variation influences follicular lymphoma susceptibility. We also found confirmatory evidence of a previously reported association between chronic lymphocytic leukemia/small lymphocytic lymphoma and rs735665 (combined P = 4.24 x 10(-9)).
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- 2010
15. Patterns of hematologic malignancies and solid tumors among 37,838 first-degree relatives of 13,896 multiple myeloma patients in Sweden
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Kristinsson, Sigurdur Y, Björkholm, Magnus, Goldin, Lynn R, Blimark, Cecilie, Mellqvist, Ulf-Henrik, Wahlin, Anders, Turesson, Ingemar, and Landgren, Ola
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Adult ,Aged, 80 and over ,Male ,Sweden ,Paraproteinemias ,Middle Aged ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Article ,Urinary Bladder Neoplasms ,Case-Control Studies ,Hematologic Neoplasms ,Neoplasms ,Humans ,Family ,Female ,Multiple Myeloma ,Aged - Abstract
There are emerging data to suggest a role for genetic factors in the pathogenesis of multiple myeloma (MM). Based on small numbers, certain solid tumors have been reported to occur more frequently among blood relatives of patients with MM. Using population-based data, we assessed risks for hematologic malignancies, monoclonal gammopathy of undetermined significance (MGUS), and solid tumors among first-degree relatives of patients with MM. We included 13,896 patients with MM and 54,365 matched controls. Also we identified first-degree relatives of patients with MM (n = 37,838) and controls (n = 151,068). Using a marginal survival model, we estimated relative risks (RRs) and 95% confidence intervals (CIs) for hematologic and solid tumors among family members of patients with MM and controls as measures of familial aggregation. Compared with relatives of controls, relatives of patients with MM had an increased risk of developing MM (RR = 2.1; 95% CI 1.6-2.9), MGUS (2.1; 1.5-3.1), acute lymphoblastic leukemia (ALL) (2.1; 1.0-4.2), any solid tumor (1.1; 1.0-1.1) and bladder cancer (1.3; 1.0-1.5). No significantly increased risk was found for other hematologic or solid malignancies. Our findings support a role for a shared susceptibility (genetic, environmental or both) that predisposes to MM, MGUS, ALL and bladder cancer.
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- 2009
16. Lymphoma risk following celiac disease diagnosed in Sweden from the mid-1970s to the early 21st Century
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Gao, Ying, Kristinsson, Sigurdur Y, Goldin, Lynn R, Björkholm, Magnus, Caporaso, Neil E, and Landgren, Ola
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Article - Published
- 2008
17. Genetic Analysis Workshop 14: microsatellite and single-nucleotide polymorphism marker loci for genome-wide scans: Introduction
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Bailey-Wilson, Joan E., Almasy, Laura, Andrade, Mariza de, Bailey, Julia, Bickeböller, Heike, Cordell, Heather J., Daw, E. Warwick, Goldin, Lynn, Goode, Ellen L., and Gray-McGuire, Courtney
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44.11 ,616.04 ,MED 243 ,MED 301 ,44.48 ,611.018 ,Präventivmedizin ,Medizinische Genetik - Abstract
Preface: This supplement to BMC Genetics contains the proceedings of the Genetic Analysis Workshop 14 (GAW14), which was held September 710, 2004, in Noordwijkerhout, The Netherlands. These workshops have been held since 1982 and now are held biennially. They serve as a forum for statisticians, epidemiologists, geneticists, and other scientists interested in these fields to introduce novel statistical methods and to evaluate and compare novel and existing methods. At each GAW, an existing dataset is selected, and a set of simulated data is devised such that statistical questions of wide and current interest may be addressed. These data are made available to scientists worldwide who then report the results of their analyses of these data at the GAW meeting. GAW attendees must submit an analysis of one of these datasets, or be a workshop organizer or a dataset provider. The purpose of these workshops is to allow the comparison of statistical methodologies for genetic epidemiology using the same, well-described datasets. More information about GAW, including details of upcoming workshops, may be found at http://www.gaworkshop.org. ... peerReviewed
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- 2005
18. Genome scan meta-analysis of schizophrenia and bipolar disorder, part 3: bipolar disorder
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Segurado, Ricardo, Detera-Wadleigh, Sevilla D., Levinson, Douglas F., Lewis, Cathryn M., Gill, Michael, Nurnberger, John I., Craddock, Nick, DePaulo, J. Raymond, Baron, Miron, Gershon, Elliot S., Ekholm, Jenny, Cichon, Sven, Turecki, Gustavo, Claes, Stephan, Kelsoe, John R., Schofield, Peter R., Badenhop, Renee F., Morisette, J., Coon, Hilary, Blackwood, Douglas, McInnes, L. Alison, Foroud, Tatiana, Edenberg, Howard J., Reich, Theodore, Rice, John P., Goate, Alison, McInnis, Melvin G., McMahon, Francis J., Badner, Judith A., Goldin, Lynn R., Bennett, Phil, Willour, Virginia L., Zandi, Peter P., Liu, Jianjun, Gilliam, Conrad, Juo, Suh-Hang, Berrettini, Wade H., Yoshikawa, Takeo, Peltonen, Leena, Lönnqvist, Jouko, Nöthen, Markus, Schumacher, Johannes, Windemuth, Christine, Rietschel, Marcella, Propping, Peter, Maier, Wolfgang, Alda, Martin, Grof, Paul, Rouleau, Guy A., Del-Favero, Jurgen, Van Broeckhoven, Christine, Mendlewicz, Julien, Adolfsson, Rolf, Spence, M. Anne, Luebbert, Hermann, Adams, Linda J., Donald, Jennifer A., Mitchell, Philip B., Barden, Nicholas, Shink, Eric, Byerley, William, Muir, Walter, Visscher, Peter M., Macgregor, Stuart, Gurling, Hugh, Kalsi, Gursharan, McQuillin, Andrew, Escamilla, Michael A., Reus, Victor I., Leon, Pedro, Freimer, Nelson B., Ewald, Henrik, Kruse, Torben A., Mors, Ole, Radhakrishna, Uppala, Blouin, Jean-Louis, Antonarakis, Stylianos E., and Akarsu, Nurten
- Abstract
Genome scans of bipolar disorder (BPD) have not produced consistent evidence for linkage. The rank-based genome scan meta-analysis (GSMA) method was applied to 18 BPD genome scan data sets in an effort to identify regions with significant support for linkage in the combined data. The two primary analyses considered available linkage data for very narrow (i.e., BP-I and schizoaffective disorderBP) and narrow (i.e., adding BP-II disorder) disease models, with the ranks weighted for sample size. A broad model (i.e., adding recurrent major depression) and unweighted analyses were also performed. No region achieved genomewide statistical significance by several simulation-based criteria. The most significant P values (
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- 2003
19. Principles of population genetics
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Goldin, Lynn R.
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Book Review - Published
- 1982
20. Human population genetics
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Goldin, Lynn R.
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Book Review - Published
- 1985
21. Genetic aspects of affective illness
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Goldin, Lynn R. and Gershon, Elliot S.
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Book Review - Published
- 1981
22. Population genetics
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Goldin, Lynn R.
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Book Review - Published
- 1982
23. Additional file 1: of Prevalence of pathogenic/likely pathogenic variants in the 24 cancer genes of the ACMG Secondary Findings v2.0 list in a large cancer cohort and ethnicity-matched controls
- Author
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Kim, Jung, Luo, Wen, Mingyi Wang, Wegman-Ostrosky, Talia, Frone, Megan, Johnston, Jennifer, Nickerson, Michael, Rotunno, Melissa, Shengchao Li, Achatz, Maria, Brodie, Seth, Dean, Michael, Andrade, Kelvin, Fortes, Fernanda, Gianferante, Matthew, Payal Khincha, McMaster, Mary, McReynolds, Lisa, Pemov, Alexander, Pinheiro, Maisa, Santiago, Karina, Alter, Blanche, Caporaso, Neil, Shahinaz Gadalla, Goldin, Lynn, Greene, Mark, Loud, Jennifer, Xiaohong Yang, Freedman, Neal, Gapstur, Susan, Gaudet, Mia, Calista, Donato, Ghiorzo, Paola, Fargnoli, Maria, Nagore, Eduardo, Peris, Ketty, Puig, Susana, Landi, Maria, Belynda Hicks, Zhu, Bin, Liu, Jia, Sampson, Joshua, Chanock, Stephen, Mirabello, Lisa, Morton, Lindsay, Biesecker, Leslie, Tucker, Margaret, Savage, Sharon, Goldstein, Alisa, and Stewart, Douglas
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3. Good health - Abstract
Supplemental Methods. Detailed methods on DNA preparation, hybridization, exome sequencing, variant calling, use of ethnicity-informative variation, quality control, and capture region matching. (PDF 233 kb)
24. Additional file 1: of Prevalence of pathogenic/likely pathogenic variants in the 24 cancer genes of the ACMG Secondary Findings v2.0 list in a large cancer cohort and ethnicity-matched controls
- Author
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Kim, Jung, Luo, Wen, Mingyi Wang, Wegman-Ostrosky, Talia, Frone, Megan, Johnston, Jennifer, Nickerson, Michael, Rotunno, Melissa, Shengchao Li, Achatz, Maria, Brodie, Seth, Dean, Michael, Andrade, Kelvin, Fortes, Fernanda, Gianferante, Matthew, Payal Khincha, McMaster, Mary, McReynolds, Lisa, Pemov, Alexander, Pinheiro, Maisa, Santiago, Karina, Alter, Blanche, Caporaso, Neil, Shahinaz Gadalla, Goldin, Lynn, Greene, Mark, Loud, Jennifer, Xiaohong Yang, Freedman, Neal, Gapstur, Susan, Gaudet, Mia, Calista, Donato, Ghiorzo, Paola, Fargnoli, Maria, Nagore, Eduardo, Peris, Ketty, Puig, Susana, Landi, Maria, Belynda Hicks, Zhu, Bin, Liu, Jia, Sampson, Joshua, Chanock, Stephen, Mirabello, Lisa, Morton, Lindsay, Biesecker, Leslie, Tucker, Margaret, Savage, Sharon, Goldstein, Alisa, and Stewart, Douglas
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3. Good health - Abstract
Supplemental Methods. Detailed methods on DNA preparation, hybridization, exome sequencing, variant calling, use of ethnicity-informative variation, quality control, and capture region matching. (PDF 233 kb)
25. Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia
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Glimelius, Bengt, Machado, Moara, Allmer, Cristine, Benavente, Yolanda, Turner, Jenny, Spinelli, John J., Kricker, Anne, Wu, Xifeng, Maynadie, Marc, Liebow, Mark, Chanock, Stephen J., Kaaks, Rudolph, McKay, James, Cozen, Wendy, Weiner, George J., Vajdic, Claire M., Chang, Ellen T., Chaffee, Kari G., Camp, Nicola J., Chirlaque, Maria-Dolores, Severson, Richard K., Weinstein, Stephanie, Shanafelt, Tait D., Ferri, Giovanni M., Gu, Jian, Ennas, Maria Grazia, Diver, W. Ryan, Zhi, Degui, Snowden, John A., Park, Ju-Hyun, Hjalgrim, Henrik, Foretova, Lenka, Becker, Nikolaus, Kelly, Rachel S., Connors, Joseph M., Morton, Lindsay M., Wang, Sophia S., Link, Brian K., Brennan, Paul, Vachon, Celine M., Clavel, Jacqueline, Ma, Baoshan, Virtamo, Jarmo, De Roos, Anneclaire J., Glenn, Martha, Vineis, Paolo, Cunningham, Julie M., Strom, Sara S., Achenbach, Sara J., Tinker, Lesley F., Holford, Theodore R., Rothman, Nathaniel, Offit, Kenneth, Lawrence, Charles, Cannon-Albright, Lisa A., Curtin, Karen, Miligi, Lucia, Burdett, Laurie, Skibola, Christine F., Kraft, Peter, Boffetta, Paolo, Arnett, Donna K., Wright, Josh, Kay, Neil E., Bracci, Paige M., Riboli, Elio, Monnereau, Alain, Southey, Melissa C., Teras, Lauren R., Ye, Yuanqing, Casabonne, Delphine, Chatterjee, Nilanjan, Goldin, Lynn R., Smedby, Karin E., Nieters, Alexandra, Vijai, Joseph, Purdue, Mark P., Gascoyne, Randy D., Weiderpass, Elisabete, Caporaso, Neil E., Zeleniuch-Jacquotte, Anne, Slager, Susan L., Zheng, Tongzhang, De Sanjose, Silvia, Call, Timothy G., Hartge, Patricia, Montalvan, Rebecca, Hutchinson, Amy, Travis, Ruth C., Leis, Jose F., Melbye, Mads, Novak, Anne J., Masala, Giovanna, Yeager, Meredith, Fraumeni, Joseph F., Leach, Justin M., Huang, Jinyan, Cocco, Pierluigi, Sala, Nuria, Giles, Graham G., Brooks-Wilson, Angela R., Cerhan, James R., Wang, Zhaoming, Milne, Roger L., Giovannucci, Edward, Maria, Ann, Albanes, Demetrius, Birmann, Brenda M., Bertrand, Kimberly A., Weinberg, J. Brice, Berndt, Sonja I., North, Kari E., Cox, Angela, Villano, Danylo J., Crouch, Simon, Jackson, Rebecca D., Adami, Hans-Olov, Holly, Elizabeth A., Zhang, Yawei, Staines, Anthony, Vermeulen, Roel C.H., Liang, Liming, Lan, Qing, Norman, Aaron D., Riby, Jacques, and Conde, Lucia
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3. Good health - Abstract
Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P=2.55 × 10−11), 6p25.2 (rs73718779, SERPINB6, P=1.97 × 10−8) and 3q28 (rs9815073, LPP, P=3.62 × 10−8), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P=1.00 × 10−11) in the combined analysis. We find suggestive evidence (P
26. Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia
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Clavel, Jacqueline, Harris, Robert J., Boffetta, Paolo, De Sanjose, Silvia, Clot, Guillem, Mansouri, Larry, Campo, Elias, Vineis, Paolo, Giles, Graham G., Slager, Susan, Marr, Helen, Jackson, Rebecca D., Teras, Lauren R., Houlston, Richard, Bracci, Paige M., Quintela, Inés, Conde, Lucia, Bailey, James R., Weinstein, Stephanie, Glimelius, Bengt, Milne, Roger L., Lawrence, Charles, Caporaso, Neil E., Kraft, Peter, Holly, Elizabeth A., Berndt, Sonja I., Hjalgrim, Henrik, McKay, James, Rothman, Nathanial, Chanock, Stephen J., Wang, Zhaoming, Skibola, Christine F., Melbye, Mads, Jayne, Sandrine, Catovsky, Daniel, Pepper, Chris, Zhang, Yawei, Miligi, Lucia, Sava, Georgina P., Monnereau, Alain, Martin-Garcia, David, Pratt, Guy, Summerfield, Geoffrey, Lan, Qing, Maynadie, Marc, Vajdic, Claire M., Dyer, Martin J. S., Goldin, Lynn R., Allsup, David J., Bea, Silvia, Majid, Aneela, Link, Brian K., Camp, Nicola J., Hall, Andrew G., Nieters, Alexandra, Ferri, Giovanni M., Law, Philip J., Rosenquist, Richard, Fraumeni, Joseph F., Jackson, Graham H., Curtin, Karen, Allan, James M., Offit, Kenneth, Cocco, Pierluigi, Southey, Melissa C., Sunter, Nicola J., Birmann, Brenda M., Morton, Lindsay M., Smedby, Karin E., Topka, Sabine, Pettitt, Andrew R., Benavente, Yolanda, Zheng, Tongzhang, Severson, Richard K., Vermeulen, Roel C. H., Cozen, Wendy, Holroyd, Amy, Riboli, Elio, Ennas, Maria Grazia, Albanes, Demetrius, Brooks-Wilson, Angela R., Carracedo, Angel, Fegan, Chris, Glenn, Martha, Spinelli, John J., Call, Timothy G., Diver, W Ryan, Liebow, Mark, Purdue, Mark P., North, Kari E., Speedy, Helen E., Joseph, Vijai, Brennan, Paul, Cerhan, James R., Tinker, Lesley F., Dearden, Claire, and Mainou-Fowler, Tryfonia
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3. Good health - Abstract
Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10−13), 1q42.13 (rs41271473, P=1.06 × 10−10), 4q24 (rs71597109, P=1.37 × 10−10), 4q35.1 (rs57214277, P=3.69 × 10−8), 6p21.31 (rs3800461, P=1.97 × 10−8), 11q23.2 (rs61904987, P=2.64 × 10−11), 18q21.1 (rs1036935, P=3.27 × 10−8), 19p13.3 (rs7254272, P=4.67 × 10−8) and 22q13.33 (rs140522, P=2.70 × 10−9). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response.
27. Detectable clonal mosaicism and its relationship to aging and cancer
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Jacobs, Kevin B., Yeager, Meredith, Zhou, Weiyin, Wacholder, Sholom, Wang, Zhaoming, Rodriguez-Santiago, Benjamin, Hutchinson, Amy, Deng, Xiang, Liu, Chenwei, Horner, Marie-Josephe, Cullen, Michael, Liao, Linda, Schwartz, Ann G., McNeill, Lorna H., Schwenn, Molly, Figueroa, Jonine D., Henderson, Brian E., Shu, Xiao-Ou, Zeleniuch-Jacquotte, Anne, Wiencke, John K., Gonzalez, Juan R., Gallinger, Steven, Fan, Jin-Hu, Thomas, Gilles, Wrensch, Margaret, Savage, Sharon A., Silverman, Debra T., Amos, Christopher I., Tang, Ze-Zhong, Sierrasesúmaga, Luis, Consonni, Dario, Albanes, Demetrius, Trichopoulos, Dimitrios, Olson, Sara H., Chow, Wong-Ho, Krogh, Vittorio, Beane Freeman, Laura, Kratz, Christian P., Holly, Elizabeth A., Blot, William J., Hallmans, Göran, Peters, Ulrike, Duell, Eric J., Brinton, Louise A., Yu, Herbert, Hoover, Robert N., Caporaso, Neil E ., Bertazzi, Pier Alberto, Chanock, Stephen J., Erickson, Ralph L., Elena, Joanne W., Visvanathan, Kala, Tobias, Geoffrey S., Rothman, Nathaniel, Gross, Myron D., Hassan, Manal, Chang, Kenneth, Cotterchio, Michelle, Johnson, Alison, Moore, Lee E., Rajaraman, Preetha, Purdue, Mark, Klein, Alison P., Wheeler, William, Wentzensen, Nicolas, Tjønneland, Anne, Arslan, Alan A., Petersen, Gloria, Chatterjee, Nilanjan, Canzian, Federico, Goggins, Michael, Landi, Maria Teresa, Kurtz, Robert C., Graubard, Barry I., Kovaks, Joseph, Marenne, Gaelle, Dean, Michael C., Giovannucci, Edward L., Wunder, Jay S., Andrulis, Irene L., Butler, Mary A., Jenab, Mazda, Bueno de Mesquita, H. Bas, Marchand, Loic Le, Carreon, Tania, Goldin, Lynn, Virtamo, Jarmo, Ruder, Avima M., Peplonska, Beata, Burdett, Laurie, Sampson, Joshua, Gorlick, Richard G., Fuchs, Charles S., Chung, Charles C., Barkauskas, Donald A., Taylor, Philip R., Haiman, Christopher A., Hunter, David J., Gapstur, Susan M., Giles, Graham G., White, Emily, Mendelsohn, Julie B., Zheng, Wei, Lissowska, Jolanta, Amundadottir, Laufey, Andersson, Ulrika, Davis, Faith G., Freedman, Neal D., Boutron-Ruault, Marie-Christine, LaCroix, Andrea, Rabe, Kari G., Hankinson, Susan E., Bracci, Paige M., McKean-Cowdin, Roberta, Weinstein, Stephanie J., Mandelson, Margaret T., Gao, Yu-Tang, Kolonel, Laurence N., Harris, Curtis C., Teras, Lauren T., Fraumeni Jr., Joseph F., Greene, Mark H., Sesso, Howard D., Mirabello, Lisa, Schwartz, Kendra L., Risch, Harvey A., Abnet, Christian C., Prokunina-Olsson, Ludmila, Garcia Closas, Montserrat, Michaud, Dominique S., Stevens, Victoria L., Signorello, Lisa B., Tucker, Margaret, Ding, Ti, Aldrich, Melinda C., Stram, Daniel, Kraft, Peter, Pérez Jurado, Luis A., Berg, Christine D., Hoffman Bolton, Judith A., Koh, Woon-Puay, Buring, Julie E., Ziegler, Regina G., Bock, Cathryn H., McWilliams, Robert R., Feychting, Maria, Goldstein, Alisa M., Hartge, Patricia, Johansen, Christoffer, Hu, Nan, Patiño García, Ana, Rotunno, Melissa, Gillanders, Elizabeth M., Rybicki, Benjamin A., Spitz, Margaret R., Riboli, Elio, Gaziano, J. Michael, Epstein, Caroline G., Khaw, Kay-Tee, Inskip, Peter D., Melin, Beatrice S., Severi, Gianluca, McGlynn, Katherine A., Wolpin, Brian M., Henriksson, Roger, Stolzenberg-Solomon, Rachael Z., Qiao, You-Lin, Gaudet, Mia M., Wu, Xifeng, Berndt, Sonja I., Yu, Kai, Hsing, Ann W., Landgren, Annelie, Wolk, Alicja, Xiang, Yong-Bing, Ahlbom, Anders, Cook, Michael B., Black, Amanda, Baris, Dalsu, Yuan, Jian-Min, Li, Donghui, Malats, Núria, Jiao, Li, Kogevinas, Manolis, Kooperberg, Charles, Villa, Olaya, Real, Francisco X., Zanetti, Krista A., and Schumacher, Fredrick
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Aging ,Envelliment ,Càncer ,Cancer - Abstract
In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of > 2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 x 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 x 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.
28. Association of polygenic risk score with the risk of chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis
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Kari G. Chaffee, Sonja I. Berndt, Alexandra Nieters, Lindsay M. Morton, Stephen J. Chanock, Neil E. Caporaso, Delphine Casabonne, Karin E. Smedby, Aaron D. Norman, Celine M. Vachon, James McKay, Pierluigi Cocco, Christine F. Skibola, Timothy G. Call, Nicola J. Camp, Martha Glenn, Jacqueline Clavel, Mark Liebow, Paolo Boffetta, James B. Johnston, John J. Spinelli, James R. Cerhan, Lynn R. Goldin, Hans-Olov Adami, Nathaniel Rothman, Yolanda Benavente, J. Brice Weinberg, Paul Brennan, Paige M. Bracci, Marc Maynadié, Dennis P. Robinson, Geffen Kleinstern, Silvia de Sanjosé, Susan L. Slager, Tait D. Shanafelt, Lucia Conde, Bengt Glimelius, Richard K. Severson, Jose F. Leis, Wendy Cozen, Claire M. Vajdic, Angela Brooks-Wilson, Mads Melbye, Henrik Hjalgrim, Karen Curtin, Neil E. Kay, Curtis A. Hanson, Alain Monnereau, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Catalan Institute of Oncology, Department of Epidemiology, Catalan Institute of Oncology (ICO), Center for Chronic Immunodeficiency (CCI), University Medical Center Freiburg, Freiburg, Germany, Dept. of Epidemiology Research, Statens Serum Institut [Copenhagen], Uppsala Universitet [Uppsala], Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Icahn School of Medicine at Mount Sinai [New York] (MSSM), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Registre des hémopathies malignes de Côte d'Or, Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Université Bourgogne Franche-Comté [COMUE] (UBFC), International Agency for Cancer Research (IACR), Mayo Clinic [Rochester], Laboratoire Interdisciplinaire de Spectroscopie Electronique (LISE), Facultés Universitaires Notre Dame de la Paix (FUNDP), Registre des hémopathies malignes de la Gironde, Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Cancer environnement (EPICENE ), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Equipe 7 : EPICEA - Epidémiologie des cancers de l'enfant et de l'adolescent (CRESS - U1153), Université Paris Descartes - Paris 5 (UPD5)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Huntsman Cancer Institute, Norris Comprehensive Cancer Center, Wayne State University [Detroit], Division of Cancer Epidemiology and Genetics, National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Emory University [Atlanta, GA], Cancer Center Karolinska [Karolinska Institutet] (CCK), Department of Psychiatry, Facultés Universitaires Notre Dame de la Paix (FUNDP) - Namur, Institut Bergonié - CRLCC Bordeaux, Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Kleinstern, Geffen, Camp, Nicola J., Goldin, Lynn R., Vachon, Celine M., Vajdic, Claire M., De Sanjose, Silvia, Weinberg, J. Brice, Benavente, Yolanda, Casabonne, Delphine, Liebow, Mark, Nieters, Alexandra, Hjalgrim, Henrik, Melbye, Mad, Glimelius, Bengt, Adami, Hans-Olov, Boffetta, Paolo, Brennan, Paul, Maynadie, Marc, McKay, Jame, Cocco, Pier Luigi, Shanafelt, Tait D., Call, Timothy G., Norman, Aaron D., Hanson, Curti, Robinson, Denni, Chaffee, Kari G., Brooks-Wilson, Angela R., Monnereau, Alain, Clavel, Jacqueline, Glenn, Martha, Curtin, Karen, Conde, Lucia, Bracci, Paige M., Morton, Lindsay M., Cozen, Wendy, Severson, Richard K., Chanock, Stephen J., Spinelli, John J., Johnston, James B., Rothman, Nathaniel, Skibola, Christine F., Leis, Jose F., Kay, Neil E., Smedby, Karin E., Berndt, Sonja I., Cerhan, James R., Caporaso, Neil, and Slager, Susan L.
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Adult ,Male ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,Lymphocytosis ,Clinical Trials and Observations ,Chronic lymphocytic leukemia ,Immunology ,Single-nucleotide polymorphism ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Polymorphism, Single Nucleotide ,Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,immune system diseases ,Internal medicine ,hemic and lymphatic diseases ,Genotype ,Odds Ratio ,medicine ,Humans ,Genetic Predisposition to Disease ,10. No inequality ,Aged ,Aged, 80 and over ,B-Lymphocytes ,business.industry ,Confounding ,Cell Biology ,Hematology ,Odds ratio ,Middle Aged ,medicine.disease ,Leukemia, Lymphocytic, Chronic, B-Cell ,3. Good health ,030104 developmental biology ,Genetic epidemiology ,Genetic Loci ,030220 oncology & carcinogenesis ,Monoclonal B-cell lymphocytosis ,Female ,medicine.symptom ,business - Abstract
IF 15.132 (2017); International audience; Inherited loci have been found to be associated with risk of chronic lymphocytic leukemia (CLL). A combined polygenic risk score (PRS) of representative single nucleotide polymorphisms (SNPs) from these loci may improve risk prediction over individual SNPs. Herein, we evaluated the association of a PRS with CLL risk and its precursor, monoclonal B-cell lymphocytosis (MBL). We assessed its validity and discriminative ability in an independent sample and evaluated effect modification and confounding by family history (FH) of hematological cancers. For discovery, we pooled genotype data on 41 representative SNPs from 1499 CLL and 2459 controls from the InterLymph Consortium. For validation, we used data from 1267 controls from Mayo Clinic and 201 CLL, 95 MBL, and 144 controls with a FH of CLL from the Genetic Epidemiology of CLL Consortium. We used odds ratios (ORs) to estimate disease associations with PRS and c-statistics to assess discriminatory accuracy. In InterLymph, the continuous PRS was strongly associated with CLL risk (OR, 2.49; P = 4.4 × 10-94). We replicated these findings in the Genetic Epidemiology of CLL Consortium and Mayo controls (OR, 3.02; P = 7.8 × 10-30) and observed high discrimination (c-statistic = 0.78). When jointly modeled with FH, PRS retained its significance, along with FH status. Finally, we found a highly significant association of the continuous PRS with MBL risk (OR, 2.81; P = 9.8 × 10-16). In conclusion, our validated PRS was strongly associated with CLL risk, adding information beyond FH. The PRS provides a means of identifying those individuals at greater risk for CLL as well as those at increased risk of MBL, a condition that has potential clinical impact beyond CLL.
- Published
- 2018
- Full Text
- View/download PDF
29. Two high-risk susceptibility loci at 6p25.3 and 14q32.13 for Waldenström macroglobulinemia
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Laurie Burdette, Lindsay M. Morton, Neil E. Caporaso, Sonja I. Berndt, Paolo Vineis, Stephen J. Chanock, Stephen M. Ansell, Elisabete Weiderpass, James McKay, Charles C. Chung, Nisha Pradhan, James R. Cerhan, Peter Kraft, Alexandra Nieters, Lauren R. Teras, Lenka Foretova, Paul Brennan, Lesley F. Tinker, Susan L. Slager, Nilanjan Chatterjee, Jianqing Zhang, Caroline Besson, Mark P. Purdue, Zhaoming Wang, Shengchao Alfred Li, Bengt Glimelius, Paige M. Bracci, Qing Lan, Mervin M. Fansler, Jacqueline Clavel, Hans-Olov Adami, Ruth C. Travis, Karin E. Smedby, Christine F. Skibola, Silvia de Sanjosé, Edward Giovannucci, Akinyemi I. Ojesina, Huihuang Yan, Richard K. Severson, Jonathan N. Hofmann, Paolo Boffetta, Lynn R. Goldin, Yawei Zhang, Belynda Hicks, Bryan A. Bassig, Charles E. Lawrence, Andrew L. Feldman, Nathaniel Rothman, Jacques Riby, Yolanda Benavente, Nikolaus Becker, Geffen Kleinstern, Marc Maynadié, Meredith Yeager, Henrik Hjalgrim, Rebecca D. Jackson, Joseph Vijai, Tongzhang Zheng, Roel Vermeulen, Amy K. Hutchinson, Brenda M. Birmann, Bin Zhu, Kenneth Offit, Brian K. Link, Alex Smith, Anthony Staines, Christine Mayr, Federico Canzian, Lucia Conde, Rebecca Montalvan, Elizabeth E. Brown, Wendy Cozen, Anne J. Novak, Claire M. Vajdic, Ju-Hyun Park, W. Ryan Diver, Mary L. McMaster, Mads Melbye, Ann Maria, Kari E. North, Alain Monnereau, McMaster, Mary L., Berndt, Sonja I., Zhang, Jianqing, Slager, Susan L., Li, Shengchao Alfred, Vajdic, Claire M., Smedby, Karin E., Yan, Huihuang, Birmann, Brenda M., Brown, Elizabeth E., Smith, Alex, Kleinstern, Geffen, Fansler, Mervin M., Mayr, Christine, Zhu, Bin, Chung, Charles C., Park, Ju-Hyun, Burdette, Laurie, Hicks, Belynda D., Hutchinson, Amy, Teras, Lauren R., Adami, Hans-Olov, Bracci, Paige M., McKay, Jame, Monnereau, Alain, Link, Brian K., Vermeulen, Roel C. H., Ansell, Stephen M., Maria, Ann, Diver, W. Ryan, Melbye, Mad, Ojesina, Akinyemi I., Kraft, Peter, Boffetta, Paolo, Clavel, Jacqueline, Giovannucci, Edward, Besson, Caroline M., Canzian, Federico, Travis, Ruth C., Vineis, Paolo, Weiderpass, Elisabete, Montalvan, Rebecca, Wang, Zhaoming, Yeager, Meredith, Becker, Nikolau, Benavente, Yolanda, Brennan, Paul, Foretova, Lenka, Maynadie, Marc, Nieters, Alexandra, de Sanjose, Silvia, Staines, Anthony, Conde, Lucia, Riby, Jacque, Glimelius, Bengt, Hjalgrim, Henrik, Pradhan, Nisha, Feldman, Andrew L., Novak, Anne J., Lawrence, Charle, Bassig, Bryan A., Lan, Qing, Zheng, Tongzhang, North, Kari E., Tinker, Lesley F., Cozen, Wendy, Severson, Richard K., Hofmann, Jonathan N., Zhang, Yawei, Jackson, Rebecca D., Morton, Lindsay M., Purdue, Mark P., Chatterjee, Nilanjan, Offit, Kenneth, Cerhan, James R., Chanock, Stephen J., Rothman, Nathaniel, Vijai, Joseph, Goldin, Lynn R., Skibola, Christine F., Caporaso, Neil E., National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), International Agency for Cancer Research (IACR), Equipe 7 : EPICEA - Epidémiologie des cancers de l'enfant et de l'adolescent (CRESS - U1153), Université Paris Descartes - Paris 5 (UPD5)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Department of Internal Medicine [Iowa City], Carver College of Medicine [Iowa City], University of Iowa [Iowa City]-University of Iowa [Iowa City], Mayo Clinic [Rochester], Icahn School of Medicine at Mount Sinai [New York] (MSSM), The Tisch Cancer Institute, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, Catalan Institute of Oncology (ICO-IDIBELL), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Masaryk Memorial Cancer Institute, Masaryk Memorial Cancer Institute (RECAMO), Registre des hématopathies malignes de Côte d'Or (RHEMCO), Centre d'épidémiologie des populations (CEP), Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Université de Bourgogne (UB), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Carolina Center for Genome Sciences, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Keck School of Medicine [Los Angeles], University of Southern California (USC), Wayne State University [Detroit], Yale School of Public Health (YSPH), Ohio State University [Columbus] (OSU), Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), Memorial Sloane Kettering Cancer Center [New York], Emory University [Atlanta, GA], Department of Medical and Clinical Genetics, Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Paul Brousse-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL)-Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), One Health Chemisch, dIRAS RA-2, Sub Atmospheric physics and chemistry, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Sorbonne Paris Cité (USPC), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)
- Subjects
Genotyping Techniques ,Inheritance Patterns ,Genome-wide association study ,enhanced green fluorescent protein ,Lymphoplasmacytic Lymphoma ,0302 clinical medicine ,Genes, Reporter ,genetics ,B-cell lymphoma ,lcsh:Science ,Malalties del sistema limfàtic ,1184 Genetics, developmental biology, physiology ,Waldenstrom macroglobulinemia ,Leucèmia ,chromosome 14 ,reporter gene ,3. Good health ,030220 oncology & carcinogenesis ,Science & Technology - Other Topics ,Chromosomes, Human, Pair 6 ,NON-HODGKIN-LYMPHOMA ,GERMINAL CENTER B ,Human ,Science ,Green Fluorescent Protein ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,Physics and Astronomy (all) ,LYMPHOPLASMACYTIC LYMPHOMA/WALDENSTROM MACROGLOBULINEMIA ,Genetic predisposition ,inheritance ,Humans ,Family ,GENOME-WIDE ASSOCIATION ,reproducibility ,Inheritance Pattern ,Cancer och onkologi ,Science & Technology ,Biochemistry, Genetics and Molecular Biology (all) ,VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762 ,CHRONIC LYMPHOCYTIC-LEUKEMIA ,nutritional and metabolic diseases ,Molecular Sequence Annotation ,medicine.disease ,Chromosomes Human Pair 6 ,Lymphoma ,030104 developmental biology ,Cancer and Oncology ,Immunology ,molecular genetics ,lcsh:Q ,HIGH-RESOLUTION ,0301 basic medicine ,General Physics and Astronomy ,Genome-wide association studies ,HEK293 Cell ,immune system diseases ,single nucleotide polymorphism ,Risk Factors ,Chromosomes Human Pair 14 ,hemic and lymphatic diseases ,Lymphatic diseases ,EXPRESSION PATTERNS ,FAMILIAL AGGREGATION ,Multidisciplinary ,Leukemia ,Chemistry (all) ,MicroRNA ,Waldenstroem macroglobulinemia ,Multidisciplinary Sciences ,HEK293 cell line ,miRNAs ,Waldenstrom Macroglobulinemia ,Green Fluorescent Proteins ,Reproducibility of Result ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Biology ,Malignancy ,Polymorphism, Single Nucleotide ,Chromosomes ,Cancer epidemiology ,MD Multidisciplinary ,medicine ,chromosome 6 ,Genetic Predisposition to Disease ,RAL GTPASES ,Cell Proliferation ,Chromosomes, Human, Pair 14 ,Base Sequence ,Risk Factor ,B-CELL LYMPHOMA ,Reproducibility of Results ,nucleotide sequence ,General Chemistry ,Heritability ,VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762 ,MicroRNAs ,HEK293 Cells ,Genotyping Technique ,genetic predisposition ,metabolism - 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 × 10−54) 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., Waldenström macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is a non-Hodgkin-type B cell lymphoma. Here, the authors identify two risk loci for WM/LPL in a two-stage GWAS involving a family-oversampling approach and provide evidence for a functional role of the non-coding SNP rs116446171.
- Published
- 2018
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