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101. Genome-Wide Association Study for Waldenström Macroglobulinemia Identifies Novel Susceptibility Loci

Author

McMaster, Mary L, Berndt, Sonja I, Zhang, Jianqing, Slager, Susan L, Li, Shengchao, Brown, Elizabeth E, Ekstrom-Smedby, Karin, Kleinstern, Geffen, Zhu, Bin, Chung, Charles, Burdette, Laurie, Park, Ju-Hyun, Birmann, Brenda M, Link, Brian K, McKay, James, Monnereau, Alain, Morton, Lindsay M., Nieters, Alexandra, Smith, Alex, Vermeulen, Roel, Hjalgrim, Henrik, Vajdic, Claire, Teras, Lauren, Hicks, Belynda, Chatterjee, Nilanjan, Rothman, Nathaniel, Offit, Kenneth, Cerhan, James R., Vijai, Joseph, Goldin, Lynn R, Skibola, Christine F, and Caporaso, Neil E

Published
2017
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103. Abstract 2756: Whole-exome sequencing reveals a novel germline variant in CEBPA-associated familial acute myeloid leukemia: 45-year follow-up of a large family

Author

Pathak, Anand, primary, Seipel, Katja, additional, Pemov, Alexander, additional, Dewan, Ramita, additional, Brown, Christina, additional, Ravichandran, Sarangan, additional, Luke, Brian T., additional, Yeager, Meredith, additional, Gatti, Richard A., additional, Caporaso, Neil, additional, Mulvihill, John J., additional, Goldin, Lynn, additional, Pabst, Thomas Muller, additional, McMaster, Mary Lou, additional, and Stewart, Douglas R., additional

Published
2015
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106. Characterization of Large Structural Genetic Mosaicism in Human Autosomes

Author

Machiela, Mitchell J., primary, Zhou, Weiyin, additional, Sampson, Joshua N., additional, Dean, Michael C., additional, Jacobs, Kevin B., additional, Black, Amanda, additional, Brinton, Louise A., additional, Chang, I-Shou, additional, Chen, Chu, additional, Chen, Constance, additional, Chen, Kexin, additional, Cook, Linda S., additional, Crous Bou, Marta, additional, De Vivo, Immaculata, additional, Doherty, Jennifer, additional, Friedenreich, Christine M., additional, Gaudet, Mia M., additional, Haiman, Christopher A., additional, Hankinson, Susan E., additional, Hartge, Patricia, additional, Henderson, Brian E., additional, Hong, Yun-Chul, additional, Hosgood, H. Dean, additional, Hsiung, Chao A., additional, Hu, Wei, additional, Hunter, David J., additional, Jessop, Lea, additional, Kim, Hee Nam, additional, Kim, Yeul Hong, additional, Kim, Young Tae, additional, Klein, Robert, additional, Kraft, Peter, additional, Lan, Qing, additional, Lin, Dongxin, additional, Liu, Jianjun, additional, Le Marchand, Loic, additional, Liang, Xiaolin, additional, Lissowska, Jolanta, additional, Lu, Lingeng, additional, Magliocco, Anthony M., additional, Matsuo, Keitaro, additional, Olson, Sara H., additional, Orlow, Irene, additional, Park, Jae Yong, additional, Pooler, Loreall, additional, Prescott, Jennifer, additional, Rastogi, Radhai, additional, Risch, Harvey A., additional, Schumacher, Fredrick, additional, Seow, Adeline, additional, Setiawan, Veronica Wendy, additional, Shen, Hongbing, additional, Sheng, Xin, additional, Shin, Min-Ho, additional, Shu, Xiao-Ou, additional, VanDen Berg, David, additional, Wang, Jiu-Cun, additional, Wentzensen, Nicolas, additional, Wong, Maria Pik, additional, Wu, Chen, additional, Wu, Tangchun, additional, Wu, Yi-Long, additional, Xia, Lucy, additional, Yang, Hannah P., additional, Yang, Pan-Chyr, additional, Zheng, Wei, additional, Zhou, Baosen, additional, Abnet, Christian C., additional, Albanes, Demetrius, additional, Aldrich, Melinda C., additional, Amos, Christopher, additional, Amundadottir, Laufey T., additional, Berndt, Sonja I., additional, Blot, William J., additional, Bock, Cathryn H., additional, Bracci, Paige M., additional, Burdett, Laurie, additional, Buring, Julie E., additional, Butler, Mary A., additional, Carreón, Tania, additional, Chatterjee, Nilanjan, additional, Chung, Charles C., additional, Cook, Michael B., additional, Cullen, Michael, additional, Davis, Faith G., additional, Ding, Ti, additional, Duell, Eric J., additional, Epstein, Caroline G., additional, Fan, Jin-Hu, additional, Figueroa, Jonine D., additional, Fraumeni, Joseph F., additional, Freedman, Neal D., additional, Fuchs, Charles S., additional, Gao, Yu-Tang, additional, Gapstur, Susan M., additional, Patiño-Garcia, Ana, additional, Garcia-Closas, Montserrat, additional, Gaziano, J. Michael, additional, Giles, Graham G., additional, Gillanders, Elizabeth M., additional, Giovannucci, Edward L., additional, Goldin, Lynn, additional, Goldstein, Alisa M., additional, Greene, Mark H., additional, Hallmans, Goran, additional, Harris, Curtis C., additional, Henriksson, Roger, additional, Holly, Elizabeth A., additional, Hoover, Robert N., additional, Hu, Nan, additional, Hutchinson, Amy, additional, Jenab, Mazda, additional, Johansen, Christoffer, additional, Khaw, Kay-Tee, additional, Koh, Woon-Puay, additional, Kolonel, Laurence N., additional, Kooperberg, Charles, additional, Krogh, Vittorio, additional, Kurtz, Robert C., additional, LaCroix, Andrea, additional, Landgren, Annelie, additional, Landi, Maria Teresa, additional, Li, Donghui, additional, Liao, Linda M., additional, Malats, Nuria, additional, McGlynn, Katherine A., additional, McNeill, Lorna H., additional, McWilliams, Robert R., additional, Melin, Beatrice S., additional, Mirabello, Lisa, additional, Peplonska, Beata, additional, Peters, Ulrike, additional, Petersen, Gloria M., additional, Prokunina-Olsson, Ludmila, additional, Purdue, Mark, additional, Qiao, You-Lin, additional, Rabe, Kari G., additional, Rajaraman, Preetha, additional, Real, Francisco X., additional, Riboli, Elio, additional, Rodríguez-Santiago, Benjamín, additional, Rothman, Nathaniel, additional, Ruder, Avima M., additional, Savage, Sharon A., additional, Schwartz, Ann G., additional, Schwartz, Kendra L., additional, Sesso, Howard D., additional, Severi, Gianluca, additional, Silverman, Debra T., additional, Spitz, Margaret R., additional, Stevens, Victoria L., additional, Stolzenberg-Solomon, Rachael, additional, Stram, Daniel, additional, Tang, Ze-Zhong, additional, Taylor, Philip R., additional, Teras, Lauren R., additional, Tobias, Geoffrey S., additional, Viswanathan, Kala, additional, Wacholder, Sholom, additional, Wang, Zhaoming, additional, Weinstein, Stephanie J., additional, Wheeler, William, additional, White, Emily, additional, Wiencke, John K., additional, Wolpin, Brian M., additional, Wu, Xifeng, additional, Wunder, Jay S., additional, Yu, Kai, additional, Zanetti, Krista A., additional, Zeleniuch-Jacquotte, Anne, additional, Ziegler, Regina G., additional, de Andrade, Mariza, additional, Barnes, Kathleen C., additional, Beaty, Terri H., additional, Bierut, Laura J., additional, Desch, Karl C., additional, Doheny, Kimberly F., additional, Feenstra, Bjarke, additional, Ginsburg, David, additional, Heit, John A., additional, Kang, Jae H., additional, Laurie, Cecilia A., additional, Li, Jun Z., additional, Lowe, William L., additional, Marazita, Mary L., additional, Melbye, Mads, additional, Mirel, Daniel B., additional, Murray, Jeffrey C., additional, Nelson, Sarah C., additional, Pasquale, Louis R., additional, Rice, Kenneth, additional, Wiggs, Janey L., additional, Wise, Anastasia, additional, Tucker, Margaret, additional, Pérez-Jurado, Luis A., additional, Laurie, Cathy C., additional, Caporaso, Neil E., additional, Yeager, Meredith, additional, and Chanock, Stephen J., additional

Published
2015
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108. Patterns of hematologic malignancies and solid tumors among 37,838 first-degree relatives of 13,896 multiple myeloma patients in Sweden

Author

Kristinsson, Sigurdur Y, Björkholm, Magnus, Goldin, Lynn R, Blimark, Cecilie, Mellqvist, Ulf-Henrik, Wahlin, Anders, Turesson, Ingemar, and Landgren, Ola

Subjects
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.

Published
2009

111. History of autoimmune disease is associated with impaired survival in multiple myeloma and monoclonal gammopathy of undetermined significance: a population-based study.

Author

Hultcrantz, Malin, Kristinsson, Sigurdur, Lindqvist, Ebba, Björkholm, Magnus, Landgren, Ola, Lund, Sigrún, Turesson, Ingemar, Goldin, Lynn, Lindqvist, Ebba K, Lund, Sigrún H, Björkholm, Magnus, and Kristinsson, Sigurdur Y

Subjects
AUTOIMMUNE diseases, MULTIPLE myeloma, MONOCLONAL gammopathies, SURVIVAL analysis (Biometry), CONFIDENCE intervals, POPULATION genetics, DISEASE risk factors, AUTOIMMUNE disease diagnosis, MULTIPLE myeloma diagnosis, LONGITUDINAL method, PUBLIC health surveillance, SURVIVAL, DIAGNOSIS
Abstract

Multiple myeloma (MM) is a plasma cell disorder preceded by monoclonal gammopathy of undetermined significance (MGUS). Incidence of MM and MGUS is higher among patients with autoimmune disease. The aim of this study was to determine whether a history of autoimmunity has an impact on survival in MM and MGUS. Using high-quality national Swedish registries, we identified 8367 patients with MM, 18,768 patients with MGUS, and 110,251 matched control subjects, and obtained information on previous autoimmune disease in patients and controls. Cox regression was used to calculate hazard ratios (HRs) for overall survival with 95 % confidence intervals (CIs). In patients with MM and a prior autoimmune disease, the risk of death was significantly increased, HR = 1.2 (95 % CI 1.2-1.3) compared to MM patients with no history of autoimmunity. In MGUS patients, a prior autoimmune disease was associated with a significantly 1.4-fold elevated risk of death (95 % CI 1.3-1.4). When analyzing different types of autoimmune diseases, a history of ulcerative colitis had a stronger impact on survival in MM than in controls. Our findings that a history of autoimmune disease has a negative impact on survival in MM and MGUS could be due to shared underlying common genetic factors, or that patients with a history of autoimmunity develop more severe cases of MM and MGUS, or cumulative comorbidity in the individual. Our results suggest that more attention should be paid to comorbidity as a prognostic factor in MGUS and MM, and underlines the need for studies aimed at tailoring therapy according to comorbidity. [ABSTRACT FROM AUTHOR]

Published
2017
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112. Genetic Analysis Workshop 14: microsatellite and single-nucleotide polymorphism marker loci for genome-wide scans: Introduction

Author

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

Subjects
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

Published
2005

115. Genome scan meta-analysis of schizophrenia and bipolar disorder, part 3: bipolar disorder

Author

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 (

Published
2003

116. Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia

Author

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, Mara-Dolores, Vermeulen, Roel C. H., 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., Bertrand, Kimberly A., Laden, Francine, Giovannucci, Edward, Kraft, Peter, Kricker, Anne, Turner, Jenny, Vajdic, Claire M., Ennas, Maria Grazia, Ferri, Giovanni M., Miligi, Lucia, Liang, Liming, Sampson, Joshua, Crouch, Simon, Park, Ju-Hyun, North, Kari E., Cox, Angela, Snowden, John A., Wright, Josh, Carracedo, Angel, Lopez-Otin, Carlos, Bea, Silvia, Salaverria, Itziar, Martin-Garcia, David, Campo, Elias, Fraumeni, Joseph F., Jr., de Sanjose, Silvia, Hjalgrim, Henrik, Cerhan, James R., Chanock, Stephen J., Rothman, Nathaniel, Slager, Susan L., 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, Mara-Dolores, Vermeulen, Roel C. H., 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., Bertrand, Kimberly A., Laden, Francine, Giovannucci, Edward, Kraft, Peter, Kricker, Anne, Turner, Jenny, Vajdic, Claire M., Ennas, Maria Grazia, Ferri, Giovanni M., Miligi, Lucia, Liang, Liming, Sampson, Joshua, Crouch, Simon, Park, Ju-Hyun, North, Kari E., Cox, Angela, Snowden, John A., Wright, Josh, Carracedo, Angel, Lopez-Otin, Carlos, Bea, Silvia, Salaverria, Itziar, Martin-Garcia, David, Campo, Elias, Fraumeni, Joseph F., Jr., de Sanjose, Silvia, Hjalgrim, Henrik, Cerhan, James R., Chanock, Stephen J., Rothman, Nathaniel, and Slager, Susan L.

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 x 10(-14)), 18q21.33 (BCL2, P = 7.76 x 10(-11)), 11p15.5 (C11orf21, P = 2.15 x 10(-10)), 4q25 (LEF1, P = 4.24 x 10(-10)), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P = 2.50 x 10(-9)), 9p21.3 (CDKN2B-AS1, P = 1.27 x 10(-8)), 18q21.32 (PMAIP1, P = 2.51 x 10(-8)), 15q15.1 (BMF, P = 2.71 x 10(-10)) and 2p22.2 (QPCT, P = 1.68 x 10(-8)), as well as an independent signal at an established locus (2q13, ACOXL, P = 2.08 x 10(-18)). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P = 5.40 x 10(-8)) and 5p15.33 (TERT, P = 1.92 x 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
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119. Detectable clonal mosaicism and its relationship to aging and cancer

Author

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, Epstein, Caroline G., Burdett, Laurie, Dean, Michael C., Chatterjee, Nilanjan, Sampson, Joshua, Chung, Charles C., Kovaks, Joseph, Gapstur, Susan M., Stevens, Victoria L., Teras, Lauren T., Gaudet, Mia M., Albanes, Demetrius, Weinstein, Stephanie J., Virtamo, Jarmo, Taylor, Philip R., Freedman, Neal D., Abnet, Christian C., Goldstein, Alisa M., Hu, Nan, Yu, Kai, Yuan, Jian-Min, Liao, Linda, Ding, Ti, Qiao, You-Lin, Gao, Yu-Tang, Koh, Woon-Puay, 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., Schwartz, Ann G., Signorello, Lisa B., Spitz, Margaret R., Wiencke, John K., Wrensch, Margaret, Wu, Xifeng, Zanetti, Krista A., Ziegler, Regina G., Figueroa, Jonine D., Garcia-Closas, Montserrat, Malats, Nuria, Marenne, Gaelle, Prokunina-Olsson, Ludmila, Baris, Dalsu, Schwenn, Molly, 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, Feychting, Maria, Ahlbom, Anders, Gaziano, J. Michael, Giles, Graham G., Hallmans, Goran, Hankinson, Susan E., Hartge, Patricia, Henriksson, Roger, Inskip, Peter D., Johansen, Christoffer, Landgren, Annelie, McKean-Cowdin, Roberta, Michaud, Dominique S., Melin, Beatrice S., Peters, Ulrike, Ruder, Avima M., Sesso, Howard D., Severi, Gianluca, Shu, Xiao-Ou, Visvanathan, Kala, White, Emily, Wolk, Alicja, Zeleniuch-Jacquotte, Anne, Zheng, Wei, Silverman, Debra T., Kogevinas, Manolis, Gonzalez, Juan R., Villa, Olaya, Li, Donghui, Duell, Eric J., Risch, Harvey A., Olson, Sara H., Kooperberg, Charles, Wolpin, Brian M., Jiao, Li, Hassan, Manal, Wheeler, William, Arslan, Alan A., Bueno-de-Mesquita, H. Bas, Fuchs, Charles S., Gallinger, Steven, Gross, Myron D., Holly, Elizabeth A., Klein, Alison P., LaCroix, Andrea, 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, Krogh, Vittorio, Kurtz, Robert C., McWilliams, Robert R., Mendelsohn, Julie B., Rabe, Kari G., Riboli, Elio, Tjonneland, Anne, Tobias, Geoffrey S., Trichopoulos, Dimitrios, Elena, Joanne W., Yu, Herbert, Amundadottir, Laufey, Stolzenberg-Solomon, Rachael Z., Kraft, Peter, Schumacher, Fredrick, Stram, Daniel, Savage, Sharon A., Mirabello, Lisa, Andrulis, Irene L., Wunder, Jay S., Patino Garcia, Ana, Sierrasesumaga, Luis, Barkauskas, Donald A., Gorlick, Richard G., Purdue, Mark, Chow, Wong-Ho, Moore, Lee E., Schwartz, Kendra L., Davis, Faith G., Hsing, Ann W., Berndt, Sonja I., Black, Amanda, Wentzensen, Nicolas, Brinton, Louise A., Lissowska, Jolanta, Peplonska, Beata, McGlynn, Katherine A., Cook, Michael B., Graubard, Barry I., Kratz, Christian P., Greene, Mark H., Erickson, Ralph L., Hunter, David J., Thomas, Gilles, Hoover, Robert N., Real, Francisco X., Fraumeni, Joseph F., Jr., Caporaso, Neil E., Tucker, Margaret, Rothman, Nathaniel, Perez-Jurado, Luis A., Chanock, Stephen J., 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, Epstein, Caroline G., Burdett, Laurie, Dean, Michael C., Chatterjee, Nilanjan, Sampson, Joshua, Chung, Charles C., Kovaks, Joseph, Gapstur, Susan M., Stevens, Victoria L., Teras, Lauren T., Gaudet, Mia M., Albanes, Demetrius, Weinstein, Stephanie J., Virtamo, Jarmo, Taylor, Philip R., Freedman, Neal D., Abnet, Christian C., Goldstein, Alisa M., Hu, Nan, Yu, Kai, Yuan, Jian-Min, Liao, Linda, Ding, Ti, Qiao, You-Lin, Gao, Yu-Tang, Koh, Woon-Puay, 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., Schwartz, Ann G., Signorello, Lisa B., Spitz, Margaret R., Wiencke, John K., Wrensch, Margaret, Wu, Xifeng, Zanetti, Krista A., Ziegler, Regina G., Figueroa, Jonine D., Garcia-Closas, Montserrat, Malats, Nuria, Marenne, Gaelle, Prokunina-Olsson, Ludmila, Baris, Dalsu, Schwenn, Molly, 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, Feychting, Maria, Ahlbom, Anders, Gaziano, J. Michael, Giles, Graham G., Hallmans, Goran, Hankinson, Susan E., Hartge, Patricia, Henriksson, Roger, Inskip, Peter D., Johansen, Christoffer, Landgren, Annelie, McKean-Cowdin, Roberta, Michaud, Dominique S., Melin, Beatrice S., Peters, Ulrike, Ruder, Avima M., Sesso, Howard D., Severi, Gianluca, Shu, Xiao-Ou, Visvanathan, Kala, White, Emily, Wolk, Alicja, Zeleniuch-Jacquotte, Anne, Zheng, Wei, Silverman, Debra T., Kogevinas, Manolis, Gonzalez, Juan R., Villa, Olaya, Li, Donghui, Duell, Eric J., Risch, Harvey A., Olson, Sara H., Kooperberg, Charles, Wolpin, Brian M., Jiao, Li, Hassan, Manal, Wheeler, William, Arslan, Alan A., Bueno-de-Mesquita, H. Bas, Fuchs, Charles S., Gallinger, Steven, Gross, Myron D., Holly, Elizabeth A., Klein, Alison P., LaCroix, Andrea, 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, Krogh, Vittorio, Kurtz, Robert C., McWilliams, Robert R., Mendelsohn, Julie B., Rabe, Kari G., Riboli, Elio, Tjonneland, Anne, Tobias, Geoffrey S., Trichopoulos, Dimitrios, Elena, Joanne W., Yu, Herbert, Amundadottir, Laufey, Stolzenberg-Solomon, Rachael Z., Kraft, Peter, Schumacher, Fredrick, Stram, Daniel, Savage, Sharon A., Mirabello, Lisa, Andrulis, Irene L., Wunder, Jay S., Patino Garcia, Ana, Sierrasesumaga, Luis, Barkauskas, Donald A., Gorlick, Richard G., Purdue, Mark, Chow, Wong-Ho, Moore, Lee E., Schwartz, Kendra L., Davis, Faith G., Hsing, Ann W., Berndt, Sonja I., Black, Amanda, Wentzensen, Nicolas, Brinton, Louise A., Lissowska, Jolanta, Peplonska, Beata, McGlynn, Katherine A., Cook, Michael B., Graubard, Barry I., Kratz, Christian P., Greene, Mark H., Erickson, Ralph L., Hunter, David J., Thomas, Gilles, Hoover, Robert N., Real, Francisco X., Fraumeni, Joseph F., Jr., Caporaso, Neil E., Tucker, Margaret, Rothman, Nathaniel, Perez-Jurado, Luis A., and 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
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120. Monoclonal gammopathy of undetermined significance and risk of infections : a population-based study.

Author

Kristinsson, Sigurdur Y, Tang, Min, Pfeiffer, Ruth M, Björkholm, Magnus, Goldin, Lynn R, Blimark, Cecilie, Mellqvist, Ulf-Henrik, Wahlin, Anders, Turesson, Ingemar, Landgren, Ola, Kristinsson, Sigurdur Y, Tang, Min, Pfeiffer, Ruth M, Björkholm, Magnus, Goldin, Lynn R, Blimark, Cecilie, Mellqvist, Ulf-Henrik, Wahlin, Anders, Turesson, Ingemar, and Landgren, Ola

Abstract

No comprehensive evaluation has been conducted to assess the risk of viral and bacterial infections among patients with monoclonal gammopathy of undetermined significance. Using population-based data from Sweden, we estimated risk of infections among 5,326 MGUS patients compared to 20,161 matched controls. Patients with monoclonal gammopathy of undetermined significance had a 2-fold increased risk (P<0.05) of developing any infection at 5 and 10 years of follow-up. More specifically, patients with monoclonal gammopathy of undetermined significance had an increased risk (P<0.05) of bacterial infections (pneumonia, osteomyelitis, septicemia, pyelonephritis, cellulitis, endocarditis, and meningitis), and viral infections (influenza and herpes zoster). Patients with monoclonal gammopathy of undetermined significance with M-protein concentrations >2.5 g/dL at diagnosis had highest risks of infections; however, the risk was also increased (P<0.05) among those with concentrations <0.5 g/dL. Patients with monoclonal gammopathy of undetermined significance who developed infections had no excess risk of developing multiple myeloma. Our findings provide novel clues for the mechanisms behind infections in patients with plasma cell dyscrasias, and may have clinical implications.

Published
2012
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121. Detectable clonal mosaicism from birth to old age and its relationship to cancer

Author

Laurie, Cathy C., Laurie, Cecelia A., Rice, Kenneth, Doheny, Kimberly F., Zelnick, Leila R., McHugh, Caitlin P., Ling, Hua, Hetrick, Kurt N., Pugh, Elizabeth W., Amos, Chris, Wei, Qingyi, Wang, Li E., Lee, Jeffrey E., Barnes, Kathleen C., Hansel, Nadia N., Mathias, Rasika, Daley, Denise, Beaty, Terri H., Scott, Alan F., Ruczinski, Ingo, Scharpf, Rob B., Bierut, Laura J., Hartz, Sarah M., Landi, Maria Teresa, Freedman, Neal D., Goldin, Lynn R., Ginsburg, David, Li, Jun, Desch, Karl C., Strom, Sara S., Blot, William J., Signorello, Lisa B., Ingles, Sue A., Chanock, Stephen J., Berndt, Sonja I., Le Marchand, Loic, Henderson, Brian E., Monroe, Kristine R., Heit, John A., De Andrade, Mariza, Armasu, Sebastian M., Regnier, Cynthia, Lowe, William L., Hayes, M. Geoffrey, Marazita, Mary L., Feingold, Eleanor, Murray, Jeffrey C., Melbye, Mads, Feenstra, Bjarke, Kang, Jae H., Wiggs, Janey L., Jarvik, Gail P., McDavid, Andrew N., Seshan, Venkatraman E., Mirel, Daniel B., Crenshaw, Andrew, Sharopova, Nataliya, Wise, Anastasia, Shen, Jess, Crosslin, David R., Levine, David M., Zheng, Xiuwen, Udren, Jenna I., Bennett, Siiri, Nelson, Sarah C., Gogarten, Stephanie M., Conomos, Matthew P., Heagerty, Patrick, Manolio, Teri, Pasquale, Louis R., Haiman, Christopher A., Caporaso, Neil, Weir, Bruce S., Laurie, Cathy C., Laurie, Cecelia A., Rice, Kenneth, Doheny, Kimberly F., Zelnick, Leila R., McHugh, Caitlin P., Ling, Hua, Hetrick, Kurt N., Pugh, Elizabeth W., Amos, Chris, Wei, Qingyi, Wang, Li E., Lee, Jeffrey E., Barnes, Kathleen C., Hansel, Nadia N., Mathias, Rasika, Daley, Denise, Beaty, Terri H., Scott, Alan F., Ruczinski, Ingo, Scharpf, Rob B., Bierut, Laura J., Hartz, Sarah M., Landi, Maria Teresa, Freedman, Neal D., Goldin, Lynn R., Ginsburg, David, Li, Jun, Desch, Karl C., Strom, Sara S., Blot, William J., Signorello, Lisa B., Ingles, Sue A., Chanock, Stephen J., Berndt, Sonja I., Le Marchand, Loic, Henderson, Brian E., Monroe, Kristine R., Heit, John A., De Andrade, Mariza, Armasu, Sebastian M., Regnier, Cynthia, Lowe, William L., Hayes, M. Geoffrey, Marazita, Mary L., Feingold, Eleanor, Murray, Jeffrey C., Melbye, Mads, Feenstra, Bjarke, Kang, Jae H., Wiggs, Janey L., Jarvik, Gail P., McDavid, Andrew N., Seshan, Venkatraman E., Mirel, Daniel B., Crenshaw, Andrew, Sharopova, Nataliya, Wise, Anastasia, Shen, Jess, Crosslin, David R., Levine, David M., Zheng, Xiuwen, Udren, Jenna I., Bennett, Siiri, Nelson, Sarah C., Gogarten, Stephanie M., Conomos, Matthew P., Heagerty, Patrick, Manolio, Teri, Pasquale, Louis R., Haiman, Christopher A., Caporaso, Neil, and Weir, Bruce S.

Abstract

We detected clonal mosaicism for large chromosomal anomalies (duplications, deletions and uniparental disomy) using SNP microarray data from over 50,000 subjects recruited for genome-wide association studies. This detection method requires a relatively high frequency of cells with the same abnormal karyotype (>5-10%; presumably of clonal origin) in the presence of normal cells. The frequency of detectable clonal mosaicism in peripheral blood is low (<0.5%) from birth until 50 years of age, after which it rapidly rises to 2-3% in the elderly. Many of the mosaic anomalies are characteristic of those found in hematological cancers and identify common deleted regions with genes previously associated with these cancers. Although only 3% of subjects with detectable clonal mosaicism had any record of hematological cancer before DNA sampling, those without a previous diagnosis have an estimated tenfold higher risk of a subsequent hematological cancer (95% confidence interval = 6-18).

Published
2012

122. Treatment-related risk factors for transformation to acute myeloid leukemia and myelodysplastic syndromes in myeloproliferative neoplasms

Author

Björkholm, Magnus, Derolf, Asa R, Hultcrantz, Malin, Kristinsson, Sigurdur Y, Ekstrand, Charlotta, Goldin, Lynn R, Andreasson, Björn, Birgegård, Gunnar, Linder, Olle, Malm, Claes, Markevärn, Berit, Nilsson, Lars, Samuelsson, Jan, Granath, Fredrik, Landgren, Ola, Björkholm, Magnus, Derolf, Asa R, Hultcrantz, Malin, Kristinsson, Sigurdur Y, Ekstrand, Charlotta, Goldin, Lynn R, Andreasson, Björn, Birgegård, Gunnar, Linder, Olle, Malm, Claes, Markevärn, Berit, Nilsson, Lars, Samuelsson, Jan, Granath, Fredrik, and Landgren, Ola

Abstract

PURPOSE: Patients with myeloproliferative neoplasms (MPNs), including polycythemia vera, essential thrombocythemia, and primary myelofibrosis, have a propensity to develop acute myeloid leukemia (AML) and myelodysplastic syndromes (MDSs). Using population-based data from Sweden, we assessed the role of MPN treatment and subsequent AML/MDS risk with special focus on the leukemogenic potential of hydroxyurea (HU). METHODS: On the basis of a nationwide MPN cohort (N = 11,039), we conducted a nested case-control study, including 162 patients (153 and nine with subsequent AML and MDS diagnosis, respectively) and 242 matched controls. We obtained clinical and MPN treatment data for all patients. Using logistic regression, we calculated odds ratios (ORs) as measures of AML/MDS risk. RESULTS: Forty-one (25%) of 162 patients with MPNs with AML/MDS development were never exposed to alkylating agents, radioactive phosphorous (P(32)), or HU. Compared with patients with who were not exposed to HU, the ORs for 1 to 499 g, 500 to 999 g, more than 1,000 g of HU were 1.5 (95% CI, 0.6 to 2.4), 1.4 (95% CI, 0.6 to 3.4), and 1.3 (95% CI, 0.5 to 3.3), respectively, for AML/MDS development (not significant). Patients with MPNs who received P(32) greater than 1,000 MBq and alkylators greater than 1 g had a 4.6-fold (95% CI, 2.1 to 9.8; P = .002) and 3.4-fold (95% CI, 1.1 to 10.6; P = .015) increased risk of AML/MDS, respectively. Patients receiving two or more cytoreductive treatments had a 2.9-fold (95% CI, 1.4 to 5.9) increased risk of transformation. CONCLUSION: The risk of AML/MDS development after MPN diagnosis was significantly associated with high exposures of P(32) and alkylators but not with HU treatment. Twenty-five percent of patients with MPNs who developed AML/MDS were not exposed to cytotoxic therapy, supporting a major role for nontreatment-related factors.

Published
2011
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123. Personal and family history of immune-related conditions increase the risk of plasma cell disorders : a population-based study

Author

Lindqvist, Ebba K., Goldin, Lynn R., Landgren, Ola, Blimark, Cecilie, Mellqvist, Ulf-Henrik, Turesson, Ingemar, Wahlin, Anders, Björkholm, Magnus, Kristinsson, Sigurdur Y., Lindqvist, Ebba K., Goldin, Lynn R., Landgren, Ola, Blimark, Cecilie, Mellqvist, Ulf-Henrik, Turesson, Ingemar, Wahlin, Anders, Björkholm, Magnus, and Kristinsson, Sigurdur Y.

Abstract

The associations between immune-related conditions and multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) have previously been investigated with inconsistent results. In a large population-based study, we identified 19 112 patients with MM, 5403 patients with MGUS, 96 617 matched control subjects, and 262 931 first-degree relatives. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for the association of MM and MGUS with immune-related conditions by use of logistic regression. A personal history of all infections combined was associated with a significantly increased risk of MM (OR = 1.2; 95% CI, 1.1-1.3), and a personal history of all conditions in the categories infections (OR = 1.6; 95% CI, 1.5-1.7), inflammatory conditions (OR = 1.4; 95% CI, 1.2-1.5), and autoimmune diseases (OR = 2.1; 95% CI, 1.9-2.4) was associated with a significantly increased risk of MGUS. Several specific immune-related conditions elevated the risk of MM and/or MGUS. A family history of autoimmune disease was associated with a significantly increased risk of MGUS (OR = 1.1; 95% CI, 1.00-1.2), but not MM. Our findings suggest that immune-related conditions and/or their treatment are of importance in the etiology of MGUS and possibly MM. The association of both personal and family history of autoimmune disease with MGUS indicates the potential for shared susceptibility for these conditions. (Blood. 2011; 118(24): 6284-6291)

Published
2011
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124. Arterial and venous thrombosis in monoclonal gammopathy of undetermined significance and multiple myeloma : a population-based study

Author

Kristinsson, Sigurdur Y, Pfeiffer, Ruth M, Björkholm, Magnus, Goldin, Lynn R, Schulman, Sam, Blimark, Cecilie, Mellqvist, Ulf-Henrik, Wahlin, Anders, Turesson, Ingemar, Landgren, Ola, Kristinsson, Sigurdur Y, Pfeiffer, Ruth M, Björkholm, Magnus, Goldin, Lynn R, Schulman, Sam, Blimark, Cecilie, Mellqvist, Ulf-Henrik, Wahlin, Anders, Turesson, Ingemar, and Landgren, Ola

Abstract

Patients with multiple myeloma (MM) have an increased risk of venous thrombosis. Interestingly, excess risk of venous thromboembolism has been observed among patients with monoclonal gammopathy of undetermined significance (MGUS). Using population-based data from Sweden, we assessed the risks of venous and arterial thrombosis in 18,627 MM and 5326 MGUS patients diagnosed from 1958 to 2006, compared with 70,991 and 20,161 matched controls, respectively. At 1, 5, and 10 years after MM diagnosis, there was an increased risk of venous thrombosis: hazard ratios (95% confidence intervals) were 7.5 (6.4-8.9), 4.6 (4.1-5.1), and 4.1 (3.8-4.5), respectively. The corresponding results for arterial thrombosis were 1.9 (1.8-2.1), 1.5 (1.4-1.6), and 1.5 (1.4-1.5). At 1, 5, and 10 years after MGUS diagnosis, hazard ratios were 3.4 (2.5-4.6), 2.1 (1.7-2.5), and 2.1 (1.8-2.4) for venous thrombosis. The corresponding risks for arterial thrombosis were 1.7 (1.5-1.9), 1.3 (1.2-1.4), and 1.3 (1.3-1.4). IgG/IgA (but not IgM) MGUS patients had increased risks for venous and arterial thrombosis. Risks for thrombosis did not vary by M-protein concentration (> 10.0 g/L or < 10.0 g/L) at diagnosis. MGUS patients with (vs without) thrombosis had no excess risk of MM or Waldenström macroglobulinemia. Our findings are of relevance for future studies and for improvement of thrombosis prophylaxis strategies.

Published
2010
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125. Patterns of survival and causes of death following a diagnosis of monoclonal gammopathy of undetermined significance. A population-based study.

Author

Kristinsson, Sigurdur Y, Björkholm, Magnus, Andersson, Therese M-L, Eloranta, Sandra, Dickman, Paul W, Goldin, Lynn R, Blimark, Cecilie, Mellqvist, Ulf-Henrik, Wahlin, Anders, Turesson, Ingemar, Landgren, Ola, Kristinsson, Sigurdur Y, Björkholm, Magnus, Andersson, Therese M-L, Eloranta, Sandra, Dickman, Paul W, Goldin, Lynn R, Blimark, Cecilie, Mellqvist, Ulf-Henrik, Wahlin, Anders, Turesson, Ingemar, and Landgren, Ola

Abstract

BACKGROUND: There are limited data on survival patterns among patients with monoclonal gammopathy of undetermined significance. DESIGN AND METHODS: We compared the survival of 4,259 patients with monoclonal gammopathy of undetermined significance, collected from hematology outpatient units in Sweden, with the survival of the general population by computing relative survival ratios. We also compared causes of death in these patients with those in 16,151 matched controls. RESULTS: One-, 5-, 10-, and 15-year relative survival ratios were 0.98 (95% CI 0.97-0.99), 0.93 (0.91-0.95), 0.82 (0.79-0.84), and 0.70 (0.64-0.76), respectively. Younger age at diagnosis of the gammopathy was associated with a significantly lower excess mortality compared to that in older patients (p<0.001). The excess mortality among patients with gammopathy increased with longer follow-up (p<0.0001). IgM (versus IgG/A) gammopathy was associated with a superior survival (p=0.038). Patients with monoclonal gammopathy of undetermined significance had an increased risk of dying from multiple myeloma (hazards ratio (HR)=553; 95% CI 77-3946), Waldenström's macroglobulinemia (HR=infinity), other lymphoproliferative malignancies (6.5; 2.8-15.1), other hematologic malignancies (22.9; 8.9-58.7), amyloidosis (HR=infinity), bacterial infections (3.4; 1.7-6.7), ischemic heart disease (1.3; 1.1-1.4), other heart disorders (1.5; 1.2-1.8), other hematologic conditions (6.9; 2.7-18), liver (2.1; 1.1-4.2), and renal diseases (3.2; 2.0-4.9). CONCLUSIONS: Our finding of decreased life expectancy in patients with monoclonal gammopathy of undetermined significance, which was most pronounced in the elderly and explained by both malignant transformation and non-malignant causes, is of importance in the understanding and clinical management of this disease. The underlying mechanisms may be causally related to the gammopathy, but may also be explained by underlying disease that led to the detection of the hematologic

Published
2009
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126. Patterns of hematologic malignancies and solid tumors among 37,838 first-degree relatives of 13,896 patients with multiple myeloma in Sweden.

Author

Kristinsson, Sigurdur Y, Björkholm, Magnus, Goldin, Lynn R, Blimark, Cecilie, Mellqvist, Ulf-Henrik, Wahlin, Anders, Turesson, Ingemar, Landgren, Ola, Kristinsson, Sigurdur Y, Björkholm, Magnus, Goldin, Lynn R, Blimark, Cecilie, Mellqvist, Ulf-Henrik, Wahlin, Anders, Turesson, Ingemar, and Landgren, Ola

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.

Published
2009
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130. Mapping of the IRF8 Gene Identifies a 3′UTR Variant Associated with Risk of Chronic Lymphocytic Leukemia but not Other Common Non-Hodgkin Lymphoma Subtypes

Author

Slager, Susan L., primary, Achenbach, Sara J., additional, Asmann, Yan W., additional, Camp, Nicola J., additional, Rabe, Kari G., additional, Goldin, Lynn R., additional, Call, Timothy G., additional, Shanafelt, Tait D., additional, Kay, Neil E., additional, Cunningham, Julie M., additional, Wang, Alice H., additional, Weinberg, J. Brice, additional, Norman, Aaron D., additional, Link, Brian K., additional, Leis, Jose F., additional, Vachon, Celine M., additional, Lanasa, Mark C., additional, Caporaso, Neil E., additional, Novak, Anne J., additional, and Cerhan, James R., additional

Published
2013
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131. Genetic evidence of PTPN22 effects on chronic lymphocytic leukemia

Author

Hebbring, Scott J., primary, Slager, Susan L., additional, Epperla, Narendranath, additional, Mazza, Joseph J., additional, Ye, Zhan, additional, Zhou, Zhiyi, additional, Achenbach, Sara J., additional, Vasco, Daniel A., additional, Call, Timothy G., additional, Rabe, Kari G., additional, Kay, Neil E., additional, Caporaso, Neil E., additional, Lanasa, Mark C., additional, Camp, Nicola J., additional, Strom, Sara S., additional, Goldin, Lynn R., additional, Cerhan, James R., additional, Brilliant, Murray H., additional, and Schrodi, Steven J., additional

Published
2013
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132. Ascertainment and diagnostic accuracy for hematopoietic lymphoproliferative malignancies in Sweden 1964-2003.

Author

Turesson, Ingemar, Linet, Martha S, Bjorkholm, Magnus, Kristinsson, Sigurdur Y, Goldin, Lynn R, Caporaso, Neil E, Landgren, Ola, Turesson, Ingemar, Linet, Martha S, Bjorkholm, Magnus, Kristinsson, Sigurdur Y, Goldin, Lynn R, Caporaso, Neil E, and Landgren, Ola

Abstract

Population-based cancer registries are widely used to provide key information about cancer incidence, survival, determinants of progression and clues about pathogenesis. To substantially expand the limited data on diagnostic accuracy and completeness for lym-phoproliferative (LP) tumors in such databases, we conducted a retrospective investigation of close to 1,000 cases diagnosed during 4 decades in Sweden. We identified and reviewed medical records for 494 LP tumor patients reported to the population-based Swedish Cancer registry and 503 LP tumor patients identified from hospitals in Sweden among patients with LP tumors diagnosed during 1964-2003. The stratified samples were randomly selected from patients according to LP subtype, over 4 equal calendar periods, and among 6 selected hospitals of diverse size and from different geographic regions. We found 97.9% of reported LP tumor cases to fulfill current diagnostic criteria for having an LP tumor and observed 89.7% to have accurate LP tumor subtype. The overall completeness of non-Hodgkin lymphoma, Hodgkin lymphoma and multiple myeloma cases in the Cancer registry was 95-99% but was lower for the more indolent tumors, chronic lymphocytic leukemia (87.9%) and Waldenstrom's macroglobulinemia (68.1%). We observed increased overall under-ascertamment for patients diagnosed above age 80 (27%) and among individuals diagnosed before 1973 (12%). In conclusion the diagnostic accuracy and completeness for classically defined LP tumor entities in the Swedish Cancer registry is high. However, we found under-ascertainment of patients with indolent LP tumors, particularly among patients diagnosed at older ages, with early-stage disease and diagnosed in earlier years.

Published
2007

135. Re:Familial clustering of Hodgkin lymphoma and multiple sclerosis (multiple letters) [3]

Author

Landgren, Ola, Kerstann, Kimberly F., Gridley, Gloria, Mellemkjaer, Lene, Hemminki, Kari, Linet, Martha S., Goldin, Lynn R., Hjalgrim, Henrik, Rostgaard, Klaus, Nielsen, Nete Munk, Koch-Henriksen, Nils, Munksgaard, Lars, Storm, Hans H., Melbye, Mads, Landgren, Ola, Kerstann, Kimberly F., Gridley, Gloria, Mellemkjaer, Lene, Hemminki, Kari, Linet, Martha S., Goldin, Lynn R., Hjalgrim, Henrik, Rostgaard, Klaus, Nielsen, Nete Munk, Koch-Henriksen, Nils, Munksgaard, Lars, Storm, Hans H., and Melbye, Mads

Published
2005

136. Mood Disorders and Risk of Lung Cancer in the EAGLE Case-Control Study and in the U.S. Veterans Affairs Inpatient Cohort

Author

Capo-Ramos, David E., primary, Gao, Ying, additional, Lubin, Jay H., additional, Check, David P., additional, Goldin, Lynn R., additional, Pesatori, Angela C., additional, Consonni, Dario, additional, Bertazzi, Pier Alberto, additional, Saxon, Andrew J., additional, Bergen, Andrew W., additional, Caporaso, Neil E., additional, and Landi, Maria Teresa, additional

Published
2012
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137. Detectable clonal mosaicism from birth to old age and its relationship to cancer

Author

Laurie, Cathy C, primary, Laurie, Cecelia A, additional, Rice, Kenneth, additional, Doheny, Kimberly F, additional, Zelnick, Leila R, additional, McHugh, Caitlin P, additional, Ling, Hua, additional, Hetrick, Kurt N, additional, Pugh, Elizabeth W, additional, Amos, Chris, additional, Wei, Qingyi, additional, Wang, Li-e, additional, Lee, Jeffrey E, additional, Barnes, Kathleen C, additional, Hansel, Nadia N, additional, Mathias, Rasika, additional, Daley, Denise, additional, Beaty, Terri H, additional, Scott, Alan F, additional, Ruczinski, Ingo, additional, Scharpf, Rob B, additional, Bierut, Laura J, additional, Hartz, Sarah M, additional, Landi, Maria Teresa, additional, Freedman, Neal D, additional, Goldin, Lynn R, additional, Ginsburg, David, additional, Li, Jun, additional, Desch, Karl C, additional, Strom, Sara S, additional, Blot, William J, additional, Signorello, Lisa B, additional, Ingles, Sue A, additional, Chanock, Stephen J, additional, Berndt, Sonja I, additional, Le Marchand, Loic, additional, Henderson, Brian E, additional, Monroe, Kristine R, additional, Heit, John A, additional, de Andrade, Mariza, additional, Armasu, Sebastian M, additional, Regnier, Cynthia, additional, Lowe, William L, additional, Hayes, M Geoffrey, additional, Marazita, Mary L, additional, Feingold, Eleanor, additional, Murray, Jeffrey C, additional, Melbye, Mads, additional, Feenstra, Bjarke, additional, Kang, Jae H, additional, Wiggs, Janey L, additional, Jarvik, Gail P, additional, McDavid, Andrew N, additional, Seshan, Venkatraman E, additional, Mirel, Daniel B, additional, Crenshaw, Andrew, additional, Sharopova, Nataliya, additional, Wise, Anastasia, additional, Shen, Jess, additional, Crosslin, David R, additional, Levine, David M, additional, Zheng, Xiuwen, additional, Udren, Jenna I, additional, Bennett, Siiri, additional, Nelson, Sarah C, additional, Gogarten, Stephanie M, additional, Conomos, Matthew P, additional, Heagerty, Patrick, additional, Manolio, Teri, additional, Pasquale, Louis R, additional, Haiman, Christopher A, additional, Caporaso, Neil, additional, and Weir, Bruce S, additional

Published
2012
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138. Detectable clonal mosaicism and its relationship to aging and cancer

Author

Jacobs, Kevin B, primary, Yeager, Meredith, additional, Zhou, Weiyin, additional, Wacholder, Sholom, additional, Wang, Zhaoming, additional, Rodriguez-Santiago, Benjamin, additional, Hutchinson, Amy, additional, Deng, Xiang, additional, Liu, Chenwei, additional, Horner, Marie-Josephe, additional, Cullen, Michael, additional, Epstein, Caroline G, additional, Burdett, Laurie, additional, Dean, Michael C, additional, Chatterjee, Nilanjan, additional, Sampson, Joshua, additional, Chung, Charles C, additional, Kovaks, Joseph, additional, Gapstur, Susan M, additional, Stevens, Victoria L, additional, Teras, Lauren T, additional, Gaudet, Mia M, additional, Albanes, Demetrius, additional, Weinstein, Stephanie J, additional, Virtamo, Jarmo, additional, Taylor, Philip R, additional, Freedman, Neal D, additional, Abnet, Christian C, additional, Goldstein, Alisa M, additional, Hu, Nan, additional, Yu, Kai, additional, Yuan, Jian-Min, additional, Liao, Linda, additional, Ding, Ti, additional, Qiao, You-Lin, additional, Gao, Yu-Tang, additional, Koh, Woon-Puay, additional, Xiang, Yong-Bing, additional, Tang, Ze-Zhong, additional, Fan, Jin-Hu, additional, Aldrich, Melinda C, additional, Amos, Christopher, additional, Blot, William J, additional, Bock, Cathryn H, additional, Gillanders, Elizabeth M, additional, Harris, Curtis C, additional, Haiman, Christopher A, additional, Henderson, Brian E, additional, Kolonel, Laurence N, additional, Le Marchand, Loic, additional, McNeill, Lorna H, additional, Rybicki, Benjamin A, additional, Schwartz, Ann G, additional, Signorello, Lisa B, additional, Spitz, Margaret R, additional, Wiencke, John K, additional, Wrensch, Margaret, additional, Wu, Xifeng, additional, Zanetti, Krista A, additional, Ziegler, Regina G, additional, Figueroa, Jonine D, additional, Garcia-Closas, Montserrat, additional, Malats, Nuria, additional, Marenne, Gaelle, additional, Prokunina-Olsson, Ludmila, additional, Baris, Dalsu, additional, Schwenn, Molly, additional, Johnson, Alison, additional, Landi, Maria Teresa, additional, Goldin, Lynn, additional, Consonni, Dario, additional, Bertazzi, Pier Alberto, additional, Rotunno, Melissa, additional, Rajaraman, Preetha, additional, Andersson, Ulrika, additional, Freeman, Laura E Beane, additional, Berg, Christine D, additional, Buring, Julie E, additional, Butler, Mary A, additional, Carreon, Tania, additional, Feychting, Maria, additional, Ahlbom, Anders, additional, Gaziano, J Michael, additional, Giles, Graham G, additional, Hallmans, Goran, additional, Hankinson, Susan E, additional, Hartge, Patricia, additional, Henriksson, Roger, additional, Inskip, Peter D, additional, Johansen, Christoffer, additional, Landgren, Annelie, additional, McKean-Cowdin, Roberta, additional, Michaud, Dominique S, additional, Melin, Beatrice S, additional, Peters, Ulrike, additional, Ruder, Avima M, additional, Sesso, Howard D, additional, Severi, Gianluca, additional, Shu, Xiao-Ou, additional, Visvanathan, Kala, additional, White, Emily, additional, Wolk, Alicja, additional, Zeleniuch-Jacquotte, Anne, additional, Zheng, Wei, additional, Silverman, Debra T, additional, Kogevinas, Manolis, additional, Gonzalez, Juan R, additional, Villa, Olaya, additional, Li, Donghui, additional, Duell, Eric J, additional, Risch, Harvey A, additional, Olson, Sara H, additional, Kooperberg, Charles, additional, Wolpin, Brian M, additional, Jiao, Li, additional, Hassan, Manal, additional, Wheeler, William, additional, Arslan, Alan A, additional, Bueno-de-Mesquita, H Bas, additional, Fuchs, Charles S, additional, Gallinger, Steven, additional, Gross, Myron D, additional, Holly, Elizabeth A, additional, Klein, Alison P, additional, LaCroix, Andrea, additional, Mandelson, Margaret T, additional, Petersen, Gloria, additional, Boutron-Ruault, Marie-Christine, additional, Bracci, Paige M, additional, Canzian, Federico, additional, Chang, Kenneth, additional, Cotterchio, Michelle, additional, Giovannucci, Edward L, additional, Goggins, Michael, additional, Bolton, Judith A Hoffman, additional, Jenab, Mazda, additional, Khaw, Kay-Tee, additional, Krogh, Vittorio, additional, Kurtz, Robert C, additional, McWilliams, Robert R, additional, Mendelsohn, Julie B, additional, Rabe, Kari G, additional, Riboli, Elio, additional, Tjønneland, Anne, additional, Tobias, Geoffrey S, additional, Trichopoulos, Dimitrios, additional, Elena, Joanne W, additional, Yu, Herbert, additional, Amundadottir, Laufey, additional, Stolzenberg-Solomon, Rachael Z, additional, Kraft, Peter, additional, Schumacher, Fredrick, additional, Stram, Daniel, additional, Savage, Sharon A, additional, Mirabello, Lisa, additional, Andrulis, Irene L, additional, Wunder, Jay S, additional, García, Ana Patiño, additional, Sierrasesúmaga, Luis, additional, Barkauskas, Donald A, additional, Gorlick, Richard G, additional, Purdue, Mark, additional, Chow, Wong-Ho, additional, Moore, Lee E, additional, Schwartz, Kendra L, additional, Davis, Faith G, additional, Hsing, Ann W, additional, Berndt, Sonja I, additional, Black, Amanda, additional, Wentzensen, Nicolas, additional, Brinton, Louise A, additional, Lissowska, Jolanta, additional, Peplonska, Beata, additional, McGlynn, Katherine A, additional, Cook, Michael B, additional, Graubard, Barry I, additional, Kratz, Christian P, additional, Greene, Mark H, additional, Erickson, Ralph L, additional, Hunter, David J, additional, Thomas, Gilles, additional, Hoover, Robert N, additional, Real, Francisco X, additional, Fraumeni, Joseph F, additional, Caporaso, Neil E, additional, Tucker, Margaret, additional, Rothman, Nathaniel, additional, Pérez-Jurado, Luis A, additional, and Chanock, Stephen J, additional

Published
2012
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142. Prevalence of MBL Increases Over Time In Relatives of CLL Families,

Author

Slager, Susan L, primary, Lanasa, Mark C, additional, Allgood, Sallie D., additional, Achenbach, Sara J, additional, Norman, Aaron, additional, Vachon, Celine M, additional, Goldin, Lynn, additional, Leis, Jose F., additional, Kay, Neil, additional, Weinberg, J. Brice, additional, Rabe, Kari, additional, Call, Timothy G., additional, Cerhan, James R, additional, Shanafelt, Tait D., additional, Caporaso, Neil E, additional, Marti, Gerald E, additional, and Hanson, Curtis A., additional

Published
2011
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144. 3.15 Prevalence of MBL Increases over Time in Relatives of CLL Families

Author

Slager, Susan L., primary, Lanasa, Mark C., additional, Allgood, Sallie, additional, Achenbach, Sara J., additional, Norman, Aaron, additional, Vachon, Celine M., additional, Goldin, Lynn R., additional, Leis, Jose F., additional, Kay, Neil E., additional, Weinberg, J. Brice, additional, Rabe, Kari G., additional, Call, Timothy G., additional, Cerhan, James R., additional, Shanafelt, Tait D., additional, Caporaso, Neil E., additional, Marti, Gerald E., additional, and Hanson, Curtis A., additional

Published
2011
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146. Treatment-Related Risk Factors for Transformation to Acute Myeloid Leukemia and Myelodysplastic Syndromes in Myeloproliferative Neoplasms

Author

Björkholm, Magnus, primary, Derolf, Åsa R., additional, Hultcrantz, Malin, additional, Kristinsson, Sigurdur Y., additional, Ekstrand, Charlotta, additional, Goldin, Lynn R., additional, Andreasson, Björn, additional, Birgegård, Gunnar, additional, Linder, Olle, additional, Malm, Claes, additional, Markevärn, Berit, additional, Nilsson, Lars, additional, Samuelsson, Jan, additional, Granath, Fredrik, additional, and Landgren, Ola, additional

Published
2011
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147. A Genome-wide Association Study of Lung Cancer Identifies a Region of Chromosome 5p15 Associated with Risk for Adenocarcinoma

Author

Landi, Maria Teresa, primary, Chatterjee, Nilanjan, additional, Yu, Kai, additional, Goldin, Lynn R., additional, Goldstein, Alisa M., additional, Rotunno, Melissa, additional, Mirabello, Lisa, additional, Jacobs, Kevin, additional, Wheeler, William, additional, Yeager, Meredith, additional, Bergen, Andrew W., additional, Li, Qizhai, additional, Consonni, Dario, additional, Pesatori, Angela C., additional, Wacholder, Sholom, additional, Thun, Michael, additional, Diver, Ryan, additional, Oken, Martin, additional, Virtamo, Jarmo, additional, Albanes, Demetrius, additional, Wang, Zhaoming, additional, Burdette, Laurie, additional, Doheny, Kimberly F., additional, Pugh, Elizabeth W., additional, Laurie, Cathy, additional, Brennan, Paul, additional, Hung, Rayjean, additional, Gaborieau, Valerie, additional, McKay, James D., additional, Lathrop, Mark, additional, McLaughlin, John, additional, Wang, Ying, additional, Tsao, Ming-Sound, additional, Spitz, Margaret R., additional, Wang, Yufei, additional, Krokan, Hans, additional, Vatten, Lars, additional, Skorpen, Frank, additional, Arnesen, Egil, additional, Benhamou, Simone, additional, Bouchard, Christine, additional, Metspalu, Andres, additional, Vooder, Tonu, additional, Nelis, Mari, additional, Välk, Kristian, additional, Field, John K., additional, Chen, Chu, additional, Goodman, Gary, additional, Sulem, Patrick, additional, Thorleifsson, Gudmar, additional, Rafnar, Thorunn, additional, Eisen, Timothy, additional, Sauter, Wiebke, additional, Rosenberger, Albert, additional, Bickeböller, Heike, additional, Risch, Angela, additional, Chang-Claude, Jenny, additional, Wichmann, H. Erich, additional, Stefansson, Kari, additional, Houlston, Richard, additional, Amos, Christopher I., additional, Fraumeni, Joseph F., additional, Savage, Sharon A., additional, Bertazzi, Pier Alberto, additional, Tucker, Margaret A., additional, Chanock, Stephen, additional, and Caporaso, Neil E., additional

Published
2011
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148. Genome-wide association study identifies a novel susceptibility locus at 6p21.3 among familial CLL

Author

Slager, Susan L., primary, Rabe, Kari G., additional, Achenbach, Sara J., additional, Vachon, Celine M., additional, Goldin, Lynn R., additional, Strom, Sara S., additional, Lanasa, Mark C., additional, Spector, Logan G., additional, Rassenti, Laura Z., additional, Leis, Jose F., additional, Camp, Nicola J., additional, Glenn, Martha, additional, Kay, Neil E., additional, Cunningham, Julie M., additional, Hanson, Curtis A., additional, Marti, Gerald E., additional, Weinberg, J. Brice, additional, Morrison, Vicki A., additional, Link, Brian K., additional, Call, Timothy G., additional, Caporaso, Neil E., additional, and Cerhan, James R., additional

Published
2011
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