Inherited Risk Factors for
Childhood Leukemia are More Common in Hispanic Patients
MEMPHIS, TENN. -- Results
from a St. Jude Children's Research Hospital and the Children's Oncology Group
study pinpoint genetic basis for increased leukemia risk facing Hispanic
children and provide new hope for closing survival gap.
Hispanic
children are more likely than those from other racial and ethnic backgrounds to
be diagnosed with acute lymphoblastic leukemia (ALL) and are more likely to die
of their disease. Work led by St. Jude Children's Research Hospital scientists
has pinpointed genetic factors behind the grim statistics.
Researchers
studying a gene called ARID5B linked eight common variants of the gene to an
increased risk of not only developing pediatric ALL but of having the cancer
return after treatment. Two more ARID5B variants were tied to higher odds of
developing the disease. Investigators found that Hispanic children were up to
twice as likely as their white counterparts to inherit a high risk-version of
ARID5B.
"For
years we have known about ethnic and racial disparities in ALL risk and
outcome, but the biology behind it has been elusive. Therefore, it is truly
exciting to be able to not only pin down the biological basis but to find that
the same gene might be responsible for both differences. Children who inherit
high-risk versions of ARID5B are more likely to develop ALL in the first place
and then more likely to fail therapy," said Jun Yang, Ph.D., an assistant
member of the St. Jude Department of Pharmaceutical Sciences and the paper's
corresponding author.
The
work was done in collaboration with the Children's Oncology Group (COG), a U.S.
based research cooperative study group focused on childhood cancer research and
clinical trials. The study appears in the January 30 online edition of the
Journal of Clinical Oncology.
Multiple
factors contribute to cancer development, and inheriting a high-risk version of
ARID5B is not enough to cause the disease, Yang said. These findings set the
stage for exciting research in understanding how genetic, environmental and
other factors combine in ALL, especially in the context of racial and ethnic
disparity, he said.
"These
and other genomic studies suggest we are poised to finally make significant
progress in eliminating racial disparities in this catastrophic disease,"
Yang said. Additional work is needed to translate these findings into new
clinical tools, he added.
Each
year ALL is found in about 3,000 U.S. children, making it the most common
childhood cancer. The incidence varies by self-declared race and ethnicity with
rates for Hispanic individuals 50 percent higher than for non-Hispanic white
individuals. For this study, researchers used genetic variations rather than
individual self-report to define ancestry. White children were defined as
having greater than 95 percent European ancestry and Hispanics children as
having greater than 10 percent Native American ancestry.
Although
the work of St. Jude researchers and others is helping to close the survival
gap, Hispanic children are still less likely than children from other racial or
ethnic backgrounds to be alive five years after diagnosis.
This
study builds on the earlier St. Jude research that linked different versions of
the ARID5B gene to ALL risk.
St.
Jude and COG investigators partnered to see if variations in the ARID5B gene
help to explain differences in either the incidence or the outcome of ALL in
white and Hispanic patients. ARID5B belongs to a family of genes called
transcription factors. They play a role in the normal development of white
blood cells, which are targeted in ALL. Evidence suggests the gene also
influences how methotrexate, a key anti-leukemia drug, is metabolized.
To
find ARID5B variants related to ALL, the study compared the gene in 330
Hispanic children with ALL and 541 Hispanic individuals without ALL. Researchers
also checked ARID5B in 978 white ALL patients and 1,046 white individuals
without the cancer.
Although
the high-risk versions of ARID5B were found in both white and Hispanic
patients, those variants were 1.5 to two times more common in Hispanic children
than in white children.
Individuals
inherit two copies of every gene, one from each parent. Children with one
high-risk version of ARID5B were up to 80 percent more likely to develop ALL
than others. Inheriting two copies of a high-risk version of the gene
translated into a 3.6-fold increased ALL risk.
Researchers
also found evidence linking ARID5B variants to relapse risk in 1,605 pediatric
ALL patients enrolled in COG studies. Yang and his colleagues previously linked
that level of Native American ancestry to a higher relapse risk in Hispanic ALL
patients. Patients in this study who inherited a high-risk version of ARID5B
were 50 percent more likely to relapse than other patients. They were also more
likely to die of their cancer.
The
study's first author is Heng Xu of St. Jude. Other authors are Cheng Cheng,
Deqing Pei, Yiping Fan, Wenjian Yang, Geoff Neale, William E. Evans, Ching-Hon
Pui, and Mary Relling, all of St. Jude; Meenakshi Devidas, University of
Florida, Gainesville; Paul Scheet, University of Texas MD Anderson Cancer
Center; Esteban Gonzalez Burchard, Dara Torgerson, Celeste Eng and Mignon Loh,
all of University of California, San Francisco; Michael Dean, National Cancer
Institute; Federico Antillon, Unidad Nacional de Oncologia Pediatrica,
Guatemala; Naomi Winick, University of Texas Southwestern Medical Center; Paul
Martin, Duke University; Cheryl Willman, University of New Mexico; Bruce
Camitta, Medical College of Wisconsin; Gregory Reaman, George Washington
University, Children's National Medical Center; William Carroll, New York
University; and Stephen Hunger, University of Colorado School of Medicine and
Children's Hospital Colorado.
Yang was supported by the
American Society of Hematology Scholar Award and the Alex Lemonade Stand Foundation
for Childhood Cancer Young Investigator Award. The work was supported in part
by the National Institutes of Health, the Jeffrey Pride Foundation, CureSearch
and ALSAC.
St.
Jude Children's Research Hospital, since opening 50 years ago, St. Jude Children's
Research Hospital has changed the way the world treats childhood cancer and
other life-threatening diseases. No family ever pays St. Jude for the care
their child receives and, for every child treated here, thousands more have
been saved worldwide through St. Jude discoveries. The hospital has played a
pivotal role in pushing U.S. pediatric cancer survival rates from 20 to 80
percent overall, and is the first and only National Cancer Institute-designated
Comprehensive Cancer Center devoted to children. It is also a leader in the
research and treatment of blood disorders and infectious diseases in children.
St. Jude was founded by the late entertainer Danny Thomas, who believed that no
child should die in the dawn of life. Join that mission by visiting
www.stjude.org or following us on www.facebook.com/stjude . Follow us on
Twitter @StJudeResearch.
SOURCE St. Jude Children's
Research Hospital
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