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7. ACALABRUTINIB PLUS PEMBROLIZUMAB IN RELAPSED/REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA: A PHASE 1/2 STUDY

Author

Witzig, T.E., primary, Maddocks, K., additional, de Vos, S., additional, Lyons, R., additional, Edenfield, W., additional, Sharman, J., additional, Vose, J., additional, Yimer, H., additional, Wei, H., additional, Chan, E., additional, Patel, P., additional, Di Simone, C., additional, Gandhi, M., additional, Vaughn, J., additional, Kolibaba, K., additional, Cheson, B., additional, and Samaniego, F., additional

Published
2019
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8. ADDITION OF LENALIDOMIDE TO R-CHOP (R2CHOP) IMPROVES OUTCOMES IN NEWLY DIAGNOSED DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL): FIRST REPORT OF ECOG-ACRIN1412 A RANDOMIZED PHASE 2 US INTERGROUP STUDY OF R2CHOP VS R-CHOP

Author

Nowakowski, G.S., primary, Hong, F., additional, Scott, D.W., additional, Macon, R., additional, King, R.L., additional, Habermann, T.M., additional, Wagner-Johnston, N., additional, Casulo, C., additional, Wade, J.L., additional, Nagargoje, G.G., additional, Reynolds, C.M., additional, Cohen, J.B., additional, Khan, N., additional, Amengual, J., additional, Richards, K.L., additional, Little, R.F., additional, Leonard, J.P., additional, Friedberg, J.W., additional, Kostakoglu, L., additional, Kahl, B.S., additional, and Witzig, T.E., additional

Published
2019
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12. DNA content flow cytometry as a prognostic factor for node-positive breast cancer: the role of multiparameter ploidy analysis and specimen sonication

Author

Witzig, T.E., Gonchoroff, N.J., Therneau, T., Gilbertson, D.T., Wold, L.E., Grant, C., Grande, J., Katzmann, J.A., Ahmann, D.L., and Ingle, J.N.

Subjects
DNA -- Measurement, Diploidy -- Health aspects, Breast cancer -- Prognosis, Flow cytometry -- Diagnostic use, Cell proliferation -- Measurement, Ploidy -- Health aspects, Flow cytometry -- Methods, Health
Abstract

Despite improvements in the early diagnosis and treatment of breast cancer, one major question resists resolution: which women with early-stage breast cancer should endure chemotherapeutic treatment when only a few in every hundred actually benefit from this treatment. It would be valuable to successfully predict which women have the best prognosis and therefore do not need adjuvant chemotherapy and which women should receive this therapy to ensure their best chances for survival. One promising method for improving the accuracy of prognosis for breast cancer patients is DNA measurement. In this technique, the DNA content of tumors is measured on a cell-by-cell basis. It may be normal or abnormal, and may indicate that many cells are dividing rapidly or only a few. These measurements may correlate with the patient's prognosis. In most cases, DNA measurement is made by flow cytometry, in which cells are dribbled past lasers one-by-one to obtain optical measurements, which indicate their DNA content. The methods of data analysis most appropriate for breast cancer prognosis are still under investigation; the variability of the technique appears to be great, and different laboratories may obtain different results. The automated flow cytometer does not know if it is looking at a cell nucleus, a clump of cell nuclei, or irrelevant fragments of broken cells; consequently, the resulting data is contaminated by erroneous measurements. In a recent study, researchers attempted to use the scattering of the laser light to reduce the sources of variability in the technique. The way the laser light scatters may be used to distinguish the best measurements from the flawed ones. In examining cells from women with node-positive breast cancer, researchers found that the prognosis was worse when cells had an unusual number of chromosomes (aneuploid), better with a normal number (diploid), and best with exactly twice the normal number of chromosomes (tetraploid). Similarly, patients with indications of greater cell proliferation also had a worse prognosis. However, when the traditional prognostic indicators were included in the statistical analysis, it was found that the prognosis based on both traditional factors and the measurement of DNA was no better than the prognosis based on the traditional factors alone. (Consumer Summary produced by Reliance Medical Information, Inc.)

Published
1991

13. International Working Group consensus response evaluation criteria in lymphoma (RECIL 2017)

Author

Younes, A., primary, Hilden, P., additional, Coiffier, B., additional, Hagenbeek, A., additional, Salles, G., additional, Wilson, W., additional, Seymour, J.F., additional, Kelly, K., additional, Gribben, J., additional, Pfreunschuh, M., additional, Morschhauser, F., additional, Schoder, H., additional, Zelenetz, A.D., additional, Rademaker, J., additional, Advani, R., additional, Valente, N., additional, Fortpied, C., additional, Witzig, T.E., additional, Sehn, L.H., additional, Engert, A., additional, Fisher, R.I., additional, Zinzani, P.-L., additional, Federico, M., additional, Hutchings, M., additional, Bollard, C., additional, Trneny, M., additional, Elsayed, Y.A., additional, Tobinai, K., additional, Abramson, J.S., additional, Fowler, N., additional, Goy, A., additional, Smith, M., additional, Ansell, S., additional, Kuruvilla, J., additional, Dreyling, M., additional, Thieblemont, C., additional, Little, R.F., additional, Aurer, I., additional, Van Oers, M.H.J., additional, Takeshita, K., additional, Gopal, A., additional, Rule, S., additional, de Vos, S., additional, Kloos, I., additional, Kaminski, M.S., additional, Meignan, M., additional, Schwartz, L.H., additional, Leonard, J.P., additional, Schuster, S.J., additional, and Seshan, V.E., additional

Published
2017
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14. BEYOND MAXIMUM GRADE: A NOVEL, LONGITUDINAL TOXICITY OVER TIME (TOXT) ADVERSE EVENT ANALYSIS OF LENALIDOMIDE IN FOLLICULAR LYMPHOMA IN CALGB 50401 (ALLIANCE)

Author

Thanarajasingam, G., primary, Dueck, A.C., additional, Novotny, P.J., additional, Witzig, T.E., additional, Habermann, T.M., additional, Nowakowski, G.S., additional, Flowers, C.R., additional, Bartlett, N.L., additional, Blum, K.A., additional, Pitcher, B.N., additional, Jung, S., additional, Atherton, P.J., additional, Tan, A.D., additional, Sloan, J.A., additional, and Leonard, J.P., additional

Published
2017
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15. HOST GENETIC VARIATION IN THE TNF AND NF-ĸB PATHWAYS AND PROGNOSIS IN MANTLE CELL LYMPHOMA: AN ANALYSIS OF 2 STUDIES

Author

Wang, Y., primary, Habermann, T.M., additional, Wang, S.S., additional, Maurer, M.J., additional, Link, B.K., additional, Feldman, A.L., additional, Inwards, D.J., additional, Witzig, T.E., additional, Cozen, W., additional, Morton, L.M., additional, Rothman, N., additional, Chanock, S.J., additional, Slager, S.L., additional, and Cerhan, J.R., additional

Published
2017
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16. ROBUST: PHASE III RANDOMIZED STUDY OF LENALIDOMIDE/R-CHOP VS PLACEBO/R-CHOP IN UNTREATED ABC-TYPE DIFFUSE LARGE B-CELL LYMPHOMA AND FEASIBILITY OF CELL OF ORIGIN SUBTYPING

Author

Chiappella, A., primary, Witzig, T.E., additional, Vitolo, U., additional, Gascoyne, R., additional, Russo, J., additional, Amoroso, B., additional, Hudak, K., additional, Ogunkanmi, A., additional, Xu, Y., additional, Ruiz, W., additional, Singh, S., additional, and Nowakowski, G.S., additional

Published
2017
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20. The de-ubiquitinase UCH-L1 is an oncogene that drives the development of lymphoma in vivo by deregulating PHLPP1 and Akt signaling.

Author

Hussain, S., Foreman, O., Perkins, S.L., Witzig, T.E., Miles, R.R., Deursen, J.M.A. van, Galardy, P.J., Hussain, S., Foreman, O., Perkins, S.L., Witzig, T.E., Miles, R.R., Deursen, J.M.A. van, and Galardy, P.J.

Abstract

01 september 2010, Item does not contain fulltext, De-ubiquitinating enzymes (DUBs) can reverse the modifications catalyzed by ubiquitin ligases and as such are believed to be important regulators of a variety of cellular processes. Several members of this protein family have been associated with human cancers; however, there is little evidence for a direct link between deregulated de-ubiquitination and neoplastic transformation. Ubiquitin C-terminal hydrolase (UCH)-L1 is a DUB of unknown function that is overexpressed in several human cancers, but whether it has oncogenic properties has not been established. To address this issue, we generated mice that overexpress UCH-L1 under the control of a ubiquitous promoter. Here, we show that UCH-L1 transgenic mice are prone to malignancy, primarily lymphomas and lung tumors. Furthermore, UCH-L1 overexpression strongly accelerated lymphomagenesis in Emu-myc transgenic mice. Aberrantly expressed UCH-L1 boosts signaling through the Akt pathway by downregulating the antagonistic phosphatase PHLPP1, an event that requires its de-ubiquitinase activity. These data provide the first in vivo evidence for DUB-driven oncogenesis and suggest that UCH-L1 hyperactivity deregulates normal Akt signaling.

Published
2010

22. Bowel perforation in intestinal lymphoma: incidence and clinical features

Author

Vaidya, R., primary, Habermann, T.M., additional, Donohue, J.H., additional, Ristow, K.M., additional, Maurer, M.J., additional, Macon, W.R., additional, Colgan, J.P., additional, Inwards, D.J., additional, Ansell, S.M., additional, Porrata, L.F., additional, Micallef, I.N., additional, Johnston, P.B., additional, Markovic, S.N., additional, Thompson, C.A., additional, Nowakowski, G.S., additional, and Witzig, T.E., additional

Published
2013
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23. The Efficacy and Safety of Lenalidomide Oral Monotherapy in Patients with Mantle Cell Lymphoma Previously Treated with Bortezomib: Pooled Data from Two Phase II Studies (NHL-002 and NHL-003).

Author

Reeder, Craig B., primary, Witzig, T.E., primary, Vose, Julie M., primary, Zinzani, Pier Luigi, primary, Buckstein, Rena, primary, Haioun, Corinne, primary, Bouabdallah, Reda, primary, Polikoff, Jonathan, primary, Guo, Pingshan, primary, Ervin-Haynes, Annette, primary, Pietronigro, Dennis, primary, Zeldis, Jerome B., primary, and Czuczman, Myron S., primary

Published
2008
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24. Improvement of cast nephropathy with plasma exchange depends on the diagnosis and on reduction of serum free light chains

Author

Leung, N., primary, Gertz, M.A., additional, Zeldenrust, S.R., additional, Rajkumar, S.V., additional, Dispenzieri, A., additional, Fervenza, F.C., additional, Kumar, S., additional, Lacy, M.Q., additional, Lust, J.A., additional, Greipp, P.R., additional, Witzig, T.E., additional, Hayman, S.R., additional, Russell, S.J., additional, Kyle, R.A., additional, and Winters, J.L., additional

Published
2008
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25. The IPI Predicts Outcome in Patients with Diffuse Large B-Cell Lymphoma (DLBCL) Treated with Immunochemotherapy: A Report of the University of Iowa/Mayo Clinic SPORE

Author

Habermann, Thomas M., primary, Link, B.K., additional, Maurer, M.J., additional, Wooldridge, J.E., additional, Geyer, S.M., additional, Macon, W.R., additional, Allmer, C., additional, Ansell, S.M., additional, Witzig, T.E., additional, Weiner, G.J., additional, and Cerhan, J.R., additional

Published
2007
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26. Subcutaneous Interleukin-4 for Relapsed Non-Hodgkin's Lymphoma: A Phase Ii Trial in the North Central Cancer Treatment Group, Ncctg 91-78-51

Author

Kurtz, D.M., primary, Tschetter, L.K., additional, Allred, J.B., additional, Geyer, S.M., additional, Kurtin, P.J., additional, Putnam, W.D., additional, Rowland, K.M., additional, Wiesenfeld, M., additional, Soori, G.S., additional, Tenglin, R.C., additional, Bernath, A.M., additional, and Witzig, T.E., additional

Published
2007
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35. Effect of thalidomide therapy on bone marrow angiogenesis in multiple myeloma.

Author

Kumar, S., Witzig, T.E., Dispenzieri, A., Lacy, M.Q., Wellik, L.E., Fonseca, R., Lust, J.A., Gertz, M.A., Kyle, R.A., Greipp, P.R., and Rajkumar, S.V.

Subjects
*THALIDOMIDE, *BONE marrow, *NEOVASCULARIZATION, *MULTIPLE myeloma, *CELL transplantation, *DRUG therapy
Abstract

Bone marrow (BM) angiogenesis is increased in multiple myeloma and is an important prognostic factor for survival. Previous studies have shown that BM angiogenesis does not change following chemotherapy or stem cell transplant. Given its potential antiangiogenic effect, we evaluated if thalidomide therapy would affect the BM microvessel density (MVD). We studied BM angiogenesis in 81 patients with various disease stages treated with thalidomide with or without dexamethasone. MVD was determined as previously described. MVD was compared between pretreatment marrows and those obtained 4-6 months following therapy. The median (range) MVD pretherapy was 28 (2-116) and post-therapy was 15 (3-97). A partial or complete response was seen in 58% of patients, stable disease in 41% and progressive disease in one patient. MVD decreased significantly in responders (median decrease of 12, P<0.001). In contrast, no significant change in MVD was seen in those failing to respond to thalidomide. Unlike the lack of resolution of angiogenesis reported with other therapies, we demonstrate for the first time a significant decrease in microvessels with thalidomide therapy. Although not conclusive, this result lends further support to the hypothesis that angiogenesis is a relevant therapeutic target in myeloma.Leukemia (2004) 18, 624-627. doi:10.1038/sj.leu.2403285 Published online 29 January 2004 [ABSTRACT FROM AUTHOR]

Published
2004
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36. Expression of VEGF and its receptors by myeloma cells.

Author

Kumar, S., Witzig, T.E., Timm, M., Haug, J., Wellik, L., Fonseca, R., Greipp, P.R., and RAjkumar, S.V.

Subjects
*VASCULAR endothelium, *GROWTH factors, *BONE marrow
Abstract

Angiogenesis or new vessel formation is an essential component in the growth and progression of neoplasms and there is growing evidence of its importance in hematological malignancies including multiple myeloma (MM). Vascular endothelial growth factor (VEGF) is believed to play a role in tumor angiogenesis. We studied the expression of VEGF and its receptors (VEGFR1 or Flt-1 and VEGFR2 or Flk-1/KDR) by myeloma cell lines and plasma cells isolated from patients, using different methods. VEGF expression by the plasma cells was demonstrated by immunohistochemistry in 18 of 20 patients with MM. Enzyme-linked immunosorbent assay demonstrated VEGF secretion in all six different myeloma cell lines studied. Five patient marrow samples and seven different myeloma cell lines were then studied for VEGF mRNA expression by reverse-transcriptase polymerase chain reaction (RT-PCR), which was positive in all. We further evaluated the expression of both VEGFR1 and VEGFR2 in different myeloma cell lines and five sorted myeloma bone marrow samples by RT-PCR. All the myeloma cell lines expressed VEGFR1 and three of the cell lines expressed VEGFR2. VEGFR1 expression was detected in all and VEGFR2 in all but one of the sorted marrow samples. Increased expression of VEGF by the myeloma cells taken in the context of the suspected prognostic value of marrow angiogenesis suggests a pathogenetic role for this cytokine and presence of its receptors on myeloma cells points toward an autocrine mechanism. Demonstration of the presence of VEGFR2 in our study provides a potential biological explanation for the preclinical activity observed with VEGFR2 inhibitors.Leukemia (2003) 17, 2025-2031. doi:10.1038/sj.leu.2403084 [ABSTRACT FROM AUTHOR]

Published
2003
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38. ROBUST: First report of phase III randomized study of lenalidomide/R‐CHOP (R2‐CHOP) vs placebo/R‐CHOP in previously untreated ABC‐type diffuse large B‐cell lymphoma.

Author

Vitolo, U., Witzig, T.E., Gascoyne, R.D., Scott, D.W., Zhang, Q., Jurczak, W., Özcan, M., Hong, X., Zhu, J., Jin, J., Belada, D., Bergua, J.M., Piazza, F., Mócikova, H., Molinari, A.L., Yoon, D.H., Cavallo, F., Tani, M., Izutsu, K., and Kato, K.

Subjects
DIFFUSE large B-cell lymphomas, CORE needle biopsy
Published
2019
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39. Epstein-Barr virus-positive lymphoma in patients with inflammatory bowel disease treated with azathioprine or 6-mercaptopurine

Author

Dayharsh, G.A., Loftus, E.V., Sandborn, W.J., Tremaine, W.J., Zinsmeister, A.R., Witzig, T.E., Macon, W.R., and J. Burgart, L.

Abstract

Background & Aims:: The use of azathioprine and 6-mercaptopurine for inflammatory bowel disease increased in the early 1990s. We sought to determine the effect of this change in therapy on the risk of lymphoma in patients with inflammatory bowel disease. Methods: All patients with inflammatory bowel disease at a single tertiary care medical center who developed lymphoma between 1985-2000 were identified and the pathologic features of the lymphoma including presence of Epstein-Barr virus were determined. The patients were divided into two 8-year periods (1985-1992, 1993-2000) corresponding with the introduction of azathioprine and 6-mercaptopurine in 1993. Methods:: Eighteen patients with lymphoma were identified, 6 between 1985-1992 and 12 between 1993-2000. Six of 18 lymphomas occurred in patients treated with azathioprine or 6-mercaptopurine, all between 1993-2000. Seven patients developed Epstein-Barr virus-positive lymphoma (1 from 1985-1992, 6 from 1993-2000). Five of 7 Epstein-Barr virus-positive lymphomas occurred in patients treated with azathioprine or 6-mercaptopurine compared with 1 of 11 Epstein-Barr virus-negative lymphomas (P = 0.01). Approximately 1200 patients with inflammatory bowel disease were treated with these agents between 1993-2000. Conclusions:: Treatment of inflammatory bowel disease with azathioprine or 6-mercaptopurine appears to be associated with a small increased risk of Epstein-Barr virus-positive lymphoma.

Published
2002
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40. True T-Cell Chronic Lymphocytic Leukemia: A Morphologic and Immunophenotypic Study of 25 Cases

Author

Hoyer, J.D., Ross, C.W., Li, C.-Y., Witzig, T.E., Gascoyne, R.D., Dewald, G.W., and Hanson, C.A.

Abstract

We studied 25 T-cell chronic lymphocytic leukemia (T-CLL) cases collected over a 15-year period. Immunophenotypic analysis was performed in each case; 12 cases were evaluated by cytogenetics, and gene rearrangement studies were performed in 14 cases. The median age was 57 years with a male predominance (M:F, 15:10). The median presenting lymphocyte count was 36.3 × 109/L (range, 3.9 to 438 × 109/L). Fourteen patients (56%) had shotty adenopathy and ten (40%) had mild-to-moderate splenomegaly at presentation; four (16%) had erythematous skin lesions. The lymphocytes were predominantly small; some cases had a minor component of medium-sized cells (<10%). The nuclearxytoplasmic ratios were uniformly high with round to oval nuclei; however, a wide spectrum of nuclear outlines could be found, ranging from minimally to markedly convoluted. Nucleoli were either absent or small and inconspicuous. These lymphocytes did not have the morphology of prolymphocytes and did not contain cytoplasmic granules. Bone marrow infiltration was generally in an interstitial pattern; the degree of involvement ranged from 15% to 90%. Immunophenotyping showed that the lymphocytes were mature T-cells with a predominant CD4+immunophenotype. Three cases displayed a CD8+immunophenotype. The patients were treated with a variety of chemotherapeutic regimens with only a minimal response observed in two of 20 patients. We conclude that T-CLL is an uncommon chronic lymphoprolrfera-tive disorder (CLPD) that can be morphologically similar to B-CLL, is distinct from T-prolymphocytic leukemia, and has an aggressive clinical course that is refractory to therapy. It may also be difficult to distinguish T-CLL from other T-CLPD, especially the leukemic phase of peripheral T-cell lymphoma and some cases of Sezary syndrome.

Published
1995
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45. Monoclonal plasma cells in the peripheral blood stem cell harvest of patients with multiple myeloma is associated with shortened relapse-free survival following transplantation

Author

Gertz, M.A., Witzig, T.E., Pineda, A.A., Greipp, P.R., Kyle, R.A., and Litzow, M.R.

Subjects
Stem cells -- Physiological aspects, Multiple myeloma -- Prognosis, Transplantation of organs, tissues, etc. -- Prognosis, Business, Health care industry
Abstract

According to an abstract submitted by the authors to joint meetings of the Midwestern and Eastern regions of the American Federation for Clinical Research, to be held September 28-30, 1995 [...]

Published
1995

46. Perioperative blood transfusions do not affect disease recurrence of patients undergoing curative resection of colorectal carcinoma: a Mayo/North Central Cancer Treatment Group Study

Author

Donohue, J.H., Williams, S., Cha, S., Windschitl, H.E., Witzig, T.E., Nelson, H., Fitzgibbons, R.J., Wieand, H.S., and Moertel, C.G.

Subjects
Blood transfusion -- Physiological aspects, Colorectal cancer -- Relapse, Business, Health care industry
Abstract

According to the authors' abstract of an article published in Journal of Clinical Oncology, 'PURPOSE: To evaluate the effect of perioperative blood transfusions on colorectal cancer recurrence and patient survival. [...]

Published
1995

47. Serial studies of peripheral blood myeloma cells in patients with multiple myeloma: when is the optimal time for stem cell harvest?

Author

Witzig, T.E., Gertz, M.A., Lust, J.A., Kyle, R.A., and Greipp, P.R.

Subjects
Multiple myeloma -- Physiological aspects, Stem cells -- Health aspects, Business, Health care industry
Abstract

According to an abstract submitted by the authors to the 31st Annual Meeting of the American Society of Clinical Oncology, held May 20-23, 1995, in Los Angeles, California, 'The design [...]

Published
1995

48. Improved detection of tumor cells in peripheral blood of multiple myeloma patients using T-cell depletion with anti-CD2 coated magnetic beads

Author

Witzig, T.E., Ahmann, G., Gonchoroff, N.J., Katzmann, J.A., Kyle, R.A., and Greipp, P.R.

Subjects
Peripheral circulation -- Research, Immunofluorescence -- Methods, Cancer cells -- Measurement, Multiple myeloma -- Research, Business, Health care industry
Abstract

'Improved Detection of Tumor Cells in Peripheral Blood of Multiple Myeloma Patients Using T-Cell Depletion with Anti-CD2 Coated Magnetic Beads According to the authors' presentation to the 80th annual meeting [...]

Published
1989

49. Lupus-related single nucleotide polymorphisms and risk of diffuse large B-cell lymphoma

Author

Mariagrazia Zucca, Thomas M. Habermann, Lauren R. Teras, Joseph Vijai, Lenka Foretova, Simon Crouch, Anneclaire J. De Roos, Jacqueline Clavel, Lindsay M. Morton, Melissa C. Southey, W. Ryan Diver, Patrick M. Gaffney, James McKay, Eve Roman, Sophia S. Wang, Mark P. Purdue, Hans-Olov Adami, Gilles Salles, Jarmo Virtamo, Yan W. Asmann, Angela Brooks-Wilson, Thierry Jo Molina, Andrew D. Zelenetz, Ahmet Dogan, Kenneth Offit, Peter Kraft, Gianluca Severi, Zhaoming Wang, Tongzhang Zheng, Sonja I. Berndt, Brian K. Link, Sasha Bernatsky, Theodore R. Holford, Emanuele Angelucci, Paige M. Bracci, Martyn T. Smith, Stephen J. Chanock, Brenda M. Birmann, Hervé Ghesquières, Stephen M. Ansell, Paolo Vineis, Mads Melbye, Kari E. North, Jenny Turner, Jacques Riby, Charles E. Lawrence, Alain Monnereau, Nikolaus Becker, Lucia Conde, James R. Cerhan, Susan L. Slager, Demetrius Albanes, Henrik Hjalgrim, Hervé Tilly, Héctor A. Velásquez García, Rebecca D. Jackson, Ann E. Clarke, Elizabeth A. Holly, Robert J. Klein, Paolo Boffetta, Mark Liebow, Karin E. Smedby, Marco Rais, David G. Cox, Patricia Hartge, Rosalind Ramsey-Goldman, Rachel S. Kelly, Lesley F. Tinker, Christine F. Skibola, Wendy Cozen, Tracy Lightfoot, Anne J. Novak, Heiner Boeing, Roel Vermeulen, Claire M. Vajdic, Bengt Glimelius, Kimberly A. Bertrand, Marc Maynadie, Eleanor Kane, Nathaniel Rothman, Yolanda Benavente, Paul Brennan, Anne Tjønneland, John J. Spinelli, Qing Lan, Anne Kricker, Alex Smith, Anthony Staines, Graham G. Giles, Carrie A. Thompson, Thomas E. Witzig, Stephanie J. Weinstein, Karen H. Cotenbader, Corinne Haioun, Anne Zeleniuch-Jacquotte, Simonetta Di Lollo, Alexandra Nieters, Rudolph Kaaks, Silvia de Sanjosé, Richard K. Severson, Yawei Zhang, Research Institute of the McGill University Health Centre, 1650 Cedar Avenue, Oklahoma Medical Research Foundation, Registre des hémopathies malignes de Côte d'Or, Centre d'épidémiologie des populations ( CEP ), Université de Bourgogne ( UB ) -Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Université Bourgogne Franche-Comté ( UBFC ), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), University of Calgary, Bernatsky, S. and García, H.A.V. and Spinelli, J.J. and Gaffney, P. and Smedby, K.E. and Ramsey-Goldman, R. and Wang, S.S. and Adami, H.-O. and Albanes, D. and Angelucci, E. and Ansell, S.M. and WAsmann, Y. and Becker, N. and Benavente, Y. and Berndt, S.I. and Bertrand, K.A. and Birmann, B.M. and Boeing, H. and Boffetta, P. and Bracci, P.M. and Brennan, P. and Brooks-Wilson, A.R. and Cerhan, J.R. and Chanock, S.J. and Clavel, J. and Conde, L. and Cotenbader, K.H. and Cox, D.G. and Cozen, W. and Crouch, S. and De Roos, A.J. and De Sanjose, S. and Di Lollo, S. and Diver, W.R. and Dogan, A. and Foretova, L. and Ghesquières, H. and Giles, G.G. and Glimelius, B. and Habermann, T.M. and Haioun, C. and Hartge, P. and Hjalgrim, H. and Holford, T.R. and Holly, E.A. and Jackson, R.D. and Kaaks, R. and Kane, E. and Kelly, R.S. and Klein, R.J. and Kraft, P. and Kricker, A. and Lan, Q. and Lawrence, C. and Liebow, M. and Lightfoot, T. and Link, B.K. and Maynadie, M. and McKay, J. and Melbye, M. and Molina, T.J. and Monnereau, A. and Morton, L.M. and Nieters, A. and North, K.E. and Novak, A.J. and Offit, K. and Purdue, M.P. and Rais, M. and Riby, J. and Roman, E. and Rothman, N. and Salles, G. and Severi, G. and Severson, R.K. and Skibola, C.F. and Slager, S.L. and Smith, A. and Smith, M.T. and Southey, M.C. and Staines, A. and Teras, L.R. and Thompson, C.A. and Tilly, H. and Tinker, L.F. and Tjonneland, A. and Turner, J. and Vajdic, C.M. and Vermeulen, R.C.H. and Vijai, J. and Vineis, P. and Virtamo, J. and Wang, Z. and Weinstein, S. and Witzig, T.E. and Zelenetz, A. and Zeleniuch-Jacquotte, A. and Zhang, Y. and Zheng, T. and Zucca, M. and Clarke, A.E., McGill University Health Center [Montreal] (MUHC), Oklahoma Medical Research Foundation (OMRF), 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 Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), LS IRAS EEPI GRA (Gezh.risico-analyse), dIRAS RA-2, and dIRAS RA-I&I RA

Subjects
Oncology, medicine.medical_specialty, Immunology, Single-nucleotide polymorphism, Genome-wide association study, [SDV.CAN]Life Sciences [q-bio]/Cancer, lymphoma, Human leukocyte antigen, Bioinformatics, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 0302 clinical medicine, immune system diseases, Internal medicine, medicine, SNP, 030203 arthritis & rheumatology, Systemic lupus erythematosus, business.industry, General Medicine, medicine.disease, Systemic lupus, Lupus Nephritis, Risk of diffuse large B-cell lymphoma, 3. Good health, Lymphoma, 030220 oncology & carcinogenesis, business, Diffuse large B-cell lymphoma, IRF5, malignancy
Abstract

Objective: Determinants of the increased risk of diffuse large B-cell lymphoma (DLBCL) in SLE are unclear. Using data from a recent lymphoma genomewide association study (GWAS), we assessed whether certain lupus-related single nucleotide polymorphisms (SNPs) were also associated with DLBCL. Methods: GWAS data on European Caucasians from the International Lymphoma Epidemiology Consortium (InterLymph) provided a total of 3857 DLBCL cases and 7666 general-population controls. Data were pooled in a random-effects meta-analysis. Results: Among the 28 SLE-related SNPs investigated, the two most convincingly associated with risk of DLBCL included the CD40 SLE risk allele rs4810485 on chromosome 20q13 (OR per risk allele=1.09, 95% CI 1.02 to 1.16, p=0.0134), and the HLA SLE risk allele rs1270942 on chromosome 6p21.33 (OR per risk allele=1.17, 95% CI 1.01 to 1.36, p=0.0362). Of additional possible interest were rs2205960 and rs12537284. The rs2205960 SNP, related to a cytokine of the tumour necrosis factor superfamily TNFSF4, was associated with an OR per risk allele of 1.07, 95% CI 1.00 to 1.16, p=0.0549. The OR for the rs12537284 (chromosome 7q32, IRF5 gene) risk allele was 1.08, 95% CI 0.99 to 1.18, p=0.0765. Conclusions: These data suggest several plausible genetic links between DLBCL and SLE. © 2017 BMJ Publishing Group. All rights reserved.

Published
2017
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50. Genome-wide association study identifies five susceptibility loci for follicular lymphoma outside the HLA region

Author

Joseph Vijai, W. Ryan Diver, Degui Zhi, Brenda M. Birmann, Henrik Hjalgrim, Bruce K. Armstrong, Gianluca Severi, Pierluigi Cocco, Joseph F. Fraumeni, Xifeng Wu, Graham G. Giles, Eleanor Kane, Herve Ghesquieres, Eve Roman, Edward Giovannucci, Mads Melbye, Rudolph Kaaks, Lindsay M. Morton, Nicholas K. Akers, Elizabeth A. Holly, Liming Liang, Patrizio Mazza, Kari E. North, John J. Spinelli, Carrie A. Thompson, Bodil Ohlsson, Yuanqing Ye, Anneclaire J. De Roos, Stephen J. Chanock, Theodore R. Holford, Paul Brennan, Jianjun Liu, Roel Vermeulen, Thomas E. Witzig, Angela Brooks-Wilson, Mark P. Purdue, Ahmet Dogan, Gilles Salles, Kenneth Offit, Lucia Conde, Laurie Burdett, George J. Weiner, Anne Kricker, James McKay, Peter Kraft, Sonja I. Berndt, Attilio Gabbas, Rebecca Montalvan, Rebecca D. Jackson, Baoshan Ma, Zhaoming Wang, Patricia Hartge, Danylo J. Villano, Marc Maynadie, Mortimer J. Lacher, Lauren R. Teras, Susan L. Slager, Lenka Foretova, Rachel S. Kelly, Martha S. Linet, Brian K. Link, Jarmo Virtamo, Charles C. Chung, Anne Zeleniuch-Jacquotte, Martyn T. Smith, Tracy Lightfoot, Jacques Riby, Paolo Boffetta, Meredith Yeager, Brian C.-H. Chiu, Grzegorz S. Nowakowski, Yolanda Benavente, Bengt Glimelius, Mark Liebow, Saioa Chamosa, Charles E. Lawrence, Karin E. Smedby, Nikolaus Becker, Thomas M. Habermann, Jacqueline Clavel, Qing Lan, Alexandra Nieters, Maryjean Schenk, Sophia S. Wang, Demetrius Albanes, Lesley F. Tinker, Alex Smith, Anthony Staines, Amy Hutchinson, Wendy Cozen, Hans-Olov Adami, Anne J. Novak, Christine F. Skibola, Ann Maria, Elisabete Weiderpass, Kimberly A. Bertrand, James R. Cerhan, Maria Grazia Ennas, Claire M. Vajdic, Jinyan Huang, Paul I.W. de Bakker, Paige M. Bracci, Tongzhang Zheng, Ruth C. Travis, Paolo Vineis, Jia Nee Foo, Jennifer Turner, Alain Monnereau, Silvia de Sanjosé, Nathaniel Rothman, Yawei Zhang, Jian Gu, Skibola, C.F., Berndt, S.I., Vijai, J., Conde, L., Wang, Z., Yeager, M., De Bakker, P.I.W., Birmann, B.M., Vajdic, C.M., Foo, J.-N., Bracci, P.M., Vermeulen, R.C.H., Slager, S.L., De Sanjose, S., Wang, S.S., Linet, M.S., Salles, G., Lan, Q., Severi, G., Hjalgrim, H., Lightfoot, T., Melbye, M., Gu, J., Ghesquières, H., Link, B.K., Morton, L.M., Holly, E.A., Smith, A., Tinker, L.F., Teras, L.R., Kricker, A., Becker, N., Purdue, M.P., Spinelli, J.J., Zhang, Y., Giles, G.G., Vineis, P., Monnereau, A., Bertrand, K.A., Albanes, D., Zeleniuch-Jacquotte, A., Gabbas, A., Chung, C.C., Burdett, L., Hutchinson, A., Lawrence, C., Montalvan, R., Liang, L., Huang, J., Ma, B., Liu, J., Adami, H.-O., Glimelius, B., Ye, Y., Nowakowski, G.S., Dogan, A., Thompson, C.A., Habermann, T.M., Novak, A.J., Liebow, M., Witzig, T.E., Weiner, G.J., Schenk, M., Hartge, P., De Roos, A.J., Cozen, W., Zhi, D., Akers, N.K., Riby, J., Smith, M.T., Lacher, M., Villano, D.J., Maria, A., Roman, E., Kane, E., Jackson, R.D., North, K.E., Diver, W.R., Turner, J., Armstrong, B.K., Benavente, Y., Boffetta, P., Brennan, P., Foretova, L., Maynadie, M., Staines, A., McKay, J., Brooks-Wilson, A.R., Zheng, T., Holford, T.R., Chamosa, S., Kaaks, R., Kelly, R.S., Ohlsson, B., Travis, R.C., Weiderpass, E., Clavel, J., Giovannucci, E., Kraft, P., Virtamo, J., Mazza, P., Cocco, P., Ennas, M.G., Chiu, B.C.H., Fraumeni, J.F., Jr., Nieters, A., Offit, K., Wu, X., Cerhan, J.R., Smedby, K.E., Chanock, S.J., and Rothman, N.

Subjects
EXPRESSION, Follicular lymphoma, Single-nucleotide polymorphism, Genome-wide association study, Human leukocyte antigen, Biology, VARIANTS, Polymorphism, Single Nucleotide, follicular lymphoma, HLA Antigens, Polymorphism (computer science), Report, CLASS-I, RESOURCE, Biomarkers, Tumor, Genetics, medicine, Chromosomes, Human, Humans, TOOL, Genetic Predisposition to Disease, Genetics(clinical), PEPTIDE, Allele, Lymphoma, Follicular, Alleles, Genetics (clinical), Genetic association, SNPS, RISK, Genome-wide association, Haplotype, medicine.disease, HLA, Haplotypes, Case-Control Studies, UNIVERSITY, SET, Genome-Wide Association Study
Abstract

Genome-wide association studies (GWASs) of follicular lymphoma (FL) have previously identified human leukocyte antigen (HLA) gene variants. To identify additional FL susceptibility loci, we conducted a large-scale two-stage GWAS in 4,523 case subjects and 13,344 control subjects of European ancestry. Five non-HLA loci were associated with FL risk: 11q23.3 (rs4938573, p = 5.79 × 10 -20) near CXCR5; 11q24.3 (rs4937362, p = 6.76 × 10 -11) near ETS1; 3q28 (rs6444305, p = 1.10 × 10 -10) in LPP; 18q21.33 (rs17749561, p = 8.28 × 10 -10) near BCL2; and 8q24.21 (rs13254990, p = 1.06 × 10 -8) near PVT1. In an analysis of the HLA region, we identified four linked HLA-DRß1 multiallelic amino acids at positions 11, 13, 28, and 30 that were associated with FL risk (pomnibus = 4.20 × 10 -67 to 2.67 × 10 -70). Additional independent signals included rs17203612 in HLA class II (odds ratio [ORper-allele] = 1.44; p = 4.59 × 10 -16) and rs3130437 in HLA class I (ORper-allele = 1.23; p = 8.23 × 10 -9). Our findings further expand the number of loci associated with FL and provide evidence that multiple common variants outside the HLA region make a significant contribution to FL risk. © 2014 by The American Society of Human Genetics. All rights reserved.

Published
2016

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