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- Posted Monday July 20, 2009
UC Berkeley-TGen scientists discover gene mutation linked to increasingly common type of blood cancer
Carriers have nearly twice the risk of developing follicular
lymphoma, according to cancer's first genome-wide association
study
PHOENIX, Ariz. - July 20, 2009 - California and Arizona researchers
have identified a gene variant that carries nearly twice the risk
of developing an increasingly common type of blood cancer,
according to a study published online today by the science journal
Nature Genetics.
Investigators at the University of California, Berkeley (UC
Berkeley) and at the Translational Genomics Research Institute
(TGen) found that mutations in a gene called C6orf15, or STG, are
associated with the risk of developing follicular lymphoma. This is
a cancer of the body's disease-fighting network whose rates have
nearly doubled in the past three decades.
In the first genome-wide association study of non-Hodgkin lymphoma,
scientists at UC Berkeley and TGen identified a SNP - a single
nucleotide polymorphism - that could determine susceptibility to
follicular lymphoma. The SNP, a DNA variant within the more than
3-billion base pairs in the human genome, was identified as
rs6457327.
The study was led by Dr. Christine Skibola, Associate Adjunct
Professor of Environmental Health Sciences at UC Berkeley's School
of Public Health, and by Dr. Kevin M. Brown, an Associate
Investigator in the Integrated Cancer Genomics Division of TGen, a
Phoenix-based, non-profit biomedical research institute.
"What's exciting about this study is that we found a target in the
genome influencing the susceptibility to follicular lymphoma, which
helps us discern between three major types of lymphomas," said
Skibola, the paper's co-lead author. "That had not been done before
on a genome-wide scale. It is our hope that this research may some
day be useful in helping develop prevention, early detection and
treatment of this disease."
Follicular lymphoma accounts for as much as 30 percent of all
non-Hodgkin lymphoma, a cancer of the lymphatic system involving
the blood, bone marrow and lymph nodes. In NHL, tumors develop in
lymphocytes, a type of white blood cell. Follicular lymphoma arises
from B-cells, a specific type of white blood cell. NHL is the fifth
most common type of cancer in the U.S., and is newly diagnosed in
about 66,000 Americans each year, and annually kills nearly 20,000,
according to the National Cancer Institute.
Researchers found that, for SNP rs6457327, the presence of the G
allele - a DNA letter that varies within the genome - was
protective against follicular lymphoma, while the presence of the A
allele was predictive of an increased risk of developing follicular
lymphoma. Dr. Brown said individuals who had the A variant were
nearly twice as likely to develop follicular lymphoma.
"There's clearly a genetic component to the disease. The hope is to
one day be able to take these results, combine them with other
tests, and turn them into an individualized assessment of disease
risk," said Dr. Brown, the study's other co-lead author. "This is a
starting point."
Dr. Skibola said more studies would be needed to determine the
biological importance of other STG SNPs linked to rs6457327 that
might change the function of the gene. This could help determine
how they might influence risk of the disease.
The scientists also want to know if genetic susceptibility to
follicular lymphoma is associated with:
- Environmental factors, such as exposure to the sun.
- Conditions such as psoriasis - a chronic, autoimmune skin disease closely associated with a similar region of the genome.
- Exposure to viruses. Follicular lymphoma is associated with HIV infection, occurring in as many as 10 percent of all HIV-positive patients, according to the Lymphoma Research Foundation.
The genome-wide association study was conducted using DNA from a
population-based non-Hodgkin lymphoma case-control study in the San
Francisco Bay Area led by UC San Francisco researchers. Follow-up
validation studies were done using independent case-control studies
from Canada and Germany.
To reduce the potential for complicating factors, the more than
3,000 samples in the UC Berkeley-TGen study were from individuals
who were HIV negative. Dr. Brown said future studies could include
HIV-positive individuals, if enough samples were made
available.
This pooled genome-wide association study used by the UC
Berkeley-TGen investigators allowed them to screen more than
500,000 SNPs. The nearly 90 most significant SNPs were then
genotyped to more closely examine their association with
lymphoma.
This same pooling technique has been pioneered by TGen to screen
for genes in other studies. Additional collaborations between UC
Berkeley and TGen are planned.
"This study paves the way for more in-depth research into this type
of cancer, which is increasingly affecting more people," said Dr.
Jeffrey Trent, TGen's President and Research Director. "This study
also builds an important collaborative relationship between TGen
and UC Berkeley, one of the nation's top universities."
Other co-authors of the study include researchers from UC Berkeley,
UC San Francisco, the International Computer Science Institute in
Berkeley, the British Columbia Cancer Agency in Canada, and the
German Cancer Research Center in Germany.
*
Press Contact:
Sarah Yang
UC Berkeley Media Representative
510-643-7741
[email protected]
*
About TGen
The Translational Genomics Research Institute (TGen) is a Phoenix,
Arizona-based non-profit organization dedicated to conducting
groundbreaking research with life changing results. Research at
TGen is focused on helping patients with diseases such as cancer,
neurological disorders and diabetes. TGen is on the cutting edge of
translational research where investigators are able to unravel the
genetic components of common and complex diseases. Working with
collaborators in the scientific and medical communities, TGen
believes it can make a substantial contribution to the efficiency
and effectiveness of the translational process. TGen is affiliated
with the Van Andel Research Institute in Grand Rapids, Michigan.
For more information, visit: www.tgen.org.
Press Contact:
Steve Yozwiak
TGen Senior Science Writer
602-343-8704
[email protected]
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