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