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Global Team of Scientists, Including the Genome Institute of Singapore and Karolinska Institute Identifies Key Genetic Risk Variants for Blood Cancers Known as Lymphomas


4/21/2011 9:51:52 AM

April 21, 2011 -- An international team of scientists, epidemiologists and clinicians from Singapore, Sweden, Denmark, Canada, Australia and USA have identified key genetic risk variants that signal the likelihood of developing blood cancers known as follicular lymphoma. Follicular lymphoma is a member of the group of blood cancers known as non-Hodgkin lymphomas (NHL) or a collection of diverse blood cancers known as lymphomas. In Singapore, lymphomas are the eighth most common among men and the third most common cancer among children and young adults in Singapore1; over the period 2003-2007, there were over 2000 affected Singaporeans The breakthrough, published in the journal PloS Genetics, is likely to advance the study and development of new therapeutics for NHL.

A genome-wide association study involving more than 12,000 participants, Drs Jianjun Liu and Jia Nee Foo from the Genome Institute of Singapore (GIS), in collaboration with Drs Karin Ekström Smedby and Keith Humphreys from the Karolinska Institutet (KI), were able to confirm the existence of a previously reported genetic risk variant in the human leukocyte antigen2

(HLA) region that signals for an increased risk of contracting follicular lymphoma. This same DNA sequence variant also appears to signal for an increased predisposition to contracting diffuse large B-cell lymphoma, another subtype of NHL, suggesting that there may be shared risk factors among distinct NHL subtypes. Surprisingly, the researchers also identified a second DNA sequence variant close to the first one that signals for increased protection against follicular lymphoma. Understanding the complex and subtle changes in the DNA sequence of the HLA region that influence disease risk will lead to a better knowledge of how the human immune system reacts to foreign and cancerous cells. This could facilitate the development of drugs and treatments against lymphomas.

“The genetic risk factors underlying human diseases such as non-Hodgkin lymphoma are not well understood. Our strength in conducting massive genome-wide studies enabled us to combine information from a wide spectrum of genomes to identify these risk factors.” said Dr Jianjun Liu, Senior Group Leader and Associate Director of the Human Genetics Program in GIS. “The results of our study strongly suggest that future genetic and functional work that focused on the HLA class II region will provide important insight into the disease pathology of follicular lymphoma, diffuse large B-cell lymphoma and other subtypes of non-Hodgkin lymphoma. In addition, further studies of this region and potential interaction with environmental factors in non-Hodgkin lymphoma risk, and of non-Hodgkin lymphoma prognosis would reveal or help in the understanding of this deadly class of cancers.”

Dr Foo Jia Nee, a Research Fellow in Dr Liu’s lab, added, “We are building on the exciting results of this study by extending our research to analyse the HLA region in Singaporeans. Given the prevalence of NHL in Singapore, we expect that any findings on the risk factors for NHL among Singaporeans will have a strong impact on developing therapies to treat this group of cancers.”

“Malignant lymphomas are a group of cancers which are steadily increasing in Singapore. The causes are not well understood, and it is important to explore genetic and environmental factors that make people more susceptible, or that help us understand the pathways through which these cancers develop”, said Associate Professor Adeline Seow from the Department of Epidemiology and Public Health at National University of Singapore.

She added, “This study contributes to this knowledge by bringing together detailed genetic information from several populations, which can answer questions that individual studies are unable to.”

Research publication:

The research findings described in the press release can be found in the 21 April, 2011 advance online issue of PLoS Genetics under the title “GWAS of Follicular Lymphoma Reveals Allelic Heterogeneity at 6p21.32 and Suggests Shared Genetic Susceptibility with Diffuse Large B-cell Lymphoma”.

Authors:

Karin E. Smedby, 1 * Jia Nee Foo, 2 * Christine F. Skibola, 3 ** Hatef Darabi, 4 ** Lucia Conde, 3 Henrik Hjalgrim, 5 Vikrant Kumar, 2 Ellen T. Chang, 6,7 Nathaniel Rothman, 8 James R. Cerhan, 9 Angela Brooks-Wilson, 10,11 Emil Rehnberg, 4 Ishak D. Irwan, 2 Lars P. Ryder, 12 Peter N. Brown, 13 Paige M. Bracci, 14 Luz Agana, 7 Jaques Riby, 7 Wendy Cozen, 15 Scott Davis, 16,17 Patricia Hartge, 8 Lindsay M. Morton, 8 Richard Severson, 18,19 Sophia S. Wang, 8,20 Susan L. Slager, 9 Zachary S. Fredericksen, 9 Anne J. Novak, 9 Neil E. Kay, 9 Thomas M. Habermann, 9 Bruce Armstrong, 21 Anne Kricker, 21 Sam Milliken, 22 Mark P. Purdue, 8 Claire M. Vajdic, 23 Peter Boyle, 24 Qing Lan, 8 Shelia H. Zahm, 8 Yawei Zhang, 25 Tongzhang Zheng, 25 Stephen Leach, 26 John J. Spinelli, 10,27 Martyn T. Smith, 7 Stephen J. Chanock, 8 Leonid Padyukov, 28 Lars Alfredsson, 29 Lars Klareskog, 28 Bengt Glimelius, 30,31 Mads Melbye, 5 Edison T. Liu, 2 Hans-Olov Adami, 4,32 Keith Humphreys, 4 *** Jianjun Liu, 2 *** †

1 Dept. of Medicine, Clinical Epidemiology Unit, Karolinska Institutet, Stockholm SE-171 77, Sweden

2 Human Genetics, Genome Institute of Singapore, A*STAR, Singapore 138673

3 Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA 94720, USA

4 Dept. of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm SE-17 177, Sweden

5 Dept. of Epidemiology Research, Statens Serum Institut, Copenhagen DK-2300, Denmark

6 Cancer Prevention Institute of California, Fremont, CA 94538, USA

7 Division of Epidemiology, Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA 94305, USA

8 Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA

9 College of Medicine, Mayo Clinic, Rochester, MN 55905, USA

10 British Columbia Cancer Research Center, British Columbia Cancer Agency, Vancouver, BC V5Z 1L3, Canada

11 Dept. of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC V5A 1S6, Canada

12 Dept of Clinical Immunology, University Hospital of Copenhagen, Copenhagen DK-2100, Denmark

13 Dept. of Haematology, Copenhagen University Hospital DK-2100, Copenhagen, Denmark

14 Dept. of Epidemiology and Biostatistics, University of California, San Francisco, CA 94107, USA 2

15 Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA

16 Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA

17 University of Washington, Seattle, WA 98195, USA

18 Dept. of Family Medicine and Public Health Sciences, Wayne State University, Detroit, Michigan 48201, USA

19 Karmanos Cancer Institute, Detroit, Michigan 48201,USA

20 Division of Etiology, Beckman Research Institute and the City of Hope, Duarte, CA 91010, USA

21 Sydney School of Public Health, The University of Sydney, Sydney, NSW 2006, Australia

22 Department of Haematology, St. Vincent's Hospital, Sydney, NSW 2010, Australia

23 University of New South Wales Cancer Research Center, Prince of Wales Clinical School, Sydney, NSW 2052, Australia

24 International Prevention Research Institute, Lyon 69006, France 25 School of Public Health, Yale University, New Haven, CT 06510, USA

26 Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada

27 School of Population and Public Health, University of British Columbia, Vancouver, BC V6T 1Z3, Canada

28 Rheumatology Unit, Dept. of Medicine, Karolinska Institutet and Karolinska University Hospital Solna, Stockholm SE-171 77, Sweden

29 Institute of Environmental Medicine, Karolinska Institutet, Stockholm SE-171 77, Sweden

30 Dept. of Pathology and Oncology, Karolinska Institutet, Stockholm SE-171 77, Sweden

31 Dept. of Radiology, Oncology and Radiation Sciences, Uppsala University, Uppsala SE-751 05, Sweden

32 Dept. of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA

* These authors contributed equally as first authors

** These authors contributed equally as second authors

*** These authors contributed equally as last authors

† Correspondence should be addressed to Jianjun Liu, Human Genetics, Genome Institute of Singapore, A*STAR, Singapore 138672, Tel: +65-6808-8088 (liuj3@gis.a-star.edu.sg).

About the Genome Institute of Singapore

The Genome Institute of Singapore (GIS) is an institute of the Agency for Science, Technology and Research (A*STAR). It has a global vision that seeks to use genomic sciences to improve public health and public prosperity. Established in 2001 as a centre for genomic discovery, the GIS will pursue the integration of technology, genetics and biology towards the goal of individualized medicine. The key research areas at the GIS include Systems Biology, Stem Cell & Developmental Biology, Cancer Biology & Pharmacology, Human Genetics, Infectious Diseases, Genomic Technologies, and Computational & Mathematical Biology. The genomics infrastructure at the GIS is utilized to train new scientific talent, to function as a bridge for academic and industrial research, and to explore scientific questions of high impact.

For more information about GIS, please visit www.gis.a-star.edu.sg

About the Agency for Science, Technology and Research (A*STAR) A*STAR is the lead agency for fostering world-class scientific research and talent for a vibrant knowledge-based and innovation-driven Singapore. A*STAR oversees 14 biomedical sciences, and physical sciences and engineering research institutes, and six consortia & centres, which are located in Biopolis and Fusionopolis, as well as their immediate vicinity.

A*STAR supports Singapore's key economic clusters by providing intellectual, human and industrial capital to its partners in industry. It also supports extramural research in the universities, hospitals, research centres, and with other local and international partners.

For more information on A*STAR, please visit www.a-star.edu.sg

For more information, please contact:

Winnie Serah Lim (Ms)

Genome Institute of Singapore

Corporate Communications Tel: (65) 6808 8013

Email: limcp2@gis.a-star.edu.sg

Prudence Yeo (Ms)

Corporate Communications

Genome Institute of Singapore

Corporate Communications

Tel: (65) 6808 8010

Email: yeojp@gis.a-star.edu.sg


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