Navigation Links
Inherited Risk Factors Increase Odds of Developing Childhood Acute Lymphoblastic Leukemia
Date:8/16/2009

St. Jude Children's Research Hospital scientists lead survey of genome that identifies new genes linked to cancer risk and treatment response

MEMPHIS, Tenn., Aug. 16 /PRNewswire-USNewswire/ -- Scientists at St. Jude Children's Research Hospital have identified inherited variations in two genes that account for 37 percent of childhood acute lymphoblastic leukemia (ALL), including a gene that may help predict drug response.

The findings stem from the first complete search of the human genetic blueprint or genome to look for inherited risk factors for ALL, the most common childhood cancer. Published in the August 16 advance online issue of Nature Genetics, the work offers the first proof based on a complete survey of the human genome that inheritance plays a role in childhood ALL.

Mary Relling, Pharm.D., St. Jude Pharmaceutical Sciences chair and the paper's senior author, estimated that individuals who inherited variations in genes known as ARID5B or IKZF1 are almost twice as likely to develop ALL as those without the variations. Even then, she said, the risk remains low. ALL strikes roughly one in every 75,000 Americans. Sixty percent are children and teenagers.

"The genetic variations alone are not enough to cause the cancer. Like all cancers, pediatric ALL is a multi-factor disease," Relling explained. "But these findings may give us a handle on the mechanism of the disease and drug responsiveness to it."

Exactly the same genes, ARID5B and IKZF1, were confirmed to be altered in British children with ALL. That study was published by the Institute of Cancer Research in Surrey, England, in the same issue of Nature Genetics.

In the St. Jude study, researchers collaborated with colleagues from the Children's Oncology Group (COG), who provided additional cases for genetic analysis. COG is an international group of medical institutions that cooperate in research studies and clinical trials of childhood cancer treatment.

Researchers scanned the genomes of 441 children with ALL and a control group of 17,958 cancer-free individuals for more than 300,000 common genetic variations known as single nucleotide polymorphisms or SNPs.

The search found 18 SNPs that differed significantly in frequency between individuals with and without ALL. Six of the 18 SNPs were associated with one of the four main subtypes of ALL.

The six included two SNPs linked to the ARID5B gene. About 11 percent of those in the control group inherit the leukemia-risk ARID5B variations from both mother and father, Relling said. In comparison, the same high-risk ARID5B SNPs were found in 38 percent of patients with a type of ALL known as hyperdiploid ALL. That subtype accounts for about 20 percent of ALL patients.

Three more SNPs were traced to the genes IKZF1 and DDC, which are next to each other on chromosome 7. IKZF1 is also known as IKAROS. Earlier research from St. Jude and COG linked acquired changes in IKZF1 to an increased risk of ALL relapse. The new evidence tying inherited variation in IKZF1 to an increased risk of developing ALL underscores the need for medications targeting variations in this gene, Relling said.

Both ARID5B and IKZF1 play important roles in normal development of lymphoid or white blood cells, she said. ARID5B belongs to a family of genes that make transcription factors, which help regulate gene activity. "If they have an inherited variation that affects the function of those genes, these are plausible pathways for how a normal lymphoid cell could be disrupted and transformed into a cancer cell," Relling said.

Inherited variations in ARID5B might also influence patient response to chemotherapy, particularly to the drug methotrexate. "We found this same inherited variation also affected accumulation of the drug in leukemia cells. It accumulates better. That allows us to use a lower dose and still cure the leukemia," Relling explained. "These findings may identify a new marker that could be used to help decide on doses of methotrexate in patients with varying ARID5B status."

Scientists are not sure how the SNPs they identified influence cancer risk. But studies of variation in gene expression associated with the ARID5B gene indicate the inherited variations have a biological function. Researchers must still determine what it is.

Other authors of this paper include Lisa Trevino, Wenjian Yang, Deborah French, Geoffrey Neale, James Downing, Susana Raimondi, Ching-Hon Pui and William Evans, all of St. Jude; Stephen Hunger, University of Colorado, Denver; William Carroll, New York University Medical Center, New York; Meenakshi Devidas, University of Florida, Gainesville; and Cheryl Willman, University of New Mexico, Albuquerque.

This study was supported by the National Cancer Institute, the National Institutes of Health/National Institutes of General Medical Sciences Pharmacogenetics Research Network and ALSAC.

St. Jude Children's Research Hospital

St. Jude Children's Research Hospital is internationally recognized for its pioneering work in finding cures and saving children with cancer and other catastrophic diseases. Founded by late entertainer Danny Thomas and based in Memphis, Tenn., St. Jude freely shares its discoveries with scientific and medical communities around the world. No family ever pays for treatments not covered by insurance, and families without insurance are never asked to pay. St. Jude is financially supported by ALSAC, its fundraising organization. For more information, please visit www.stjude.org.


'/>"/>
SOURCE St. Jude Children's Research Hospital
Copyright©2009 PR Newswire.
All rights reserved

Related medicine news :

1. Gene newly linked to inherited ALS may also play role in common dementia
2. Different mutations in single gene suggest Parkinsons is primarily an inherited genetic disorder
3. Inherited melanoma risk: What you do know does help you
4. Gene Mutation Tied to Inherited Atrial Fibrillation
5. Inherited form of hearing loss stems from gene mutation
6. New findings may improve treatment of inherited breast cancer
7. Turning back the Clock in Inherited Anemias
8. Gene Mutation Tied to Inherited Fatal Lung Disease
9. Gene Mutation Linked to Inherited ALS
10. Personalized genome sequencing reveals coding error in gene for inherited pancreatic cancer
11. Study gives more proof that intelligence is largely inherited
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:8/24/2017)... ... August 24, 2017 , ... DrinkingTutors.com, a startup focused on ... tutorials, or ‘drinktorials,’ are mailed directly to teenagers’ homes every week. , ... their teenagers avoid the serious risks associated with binge drinking in high school, ...
(Date:8/23/2017)... ... ... Drs. Steven White and Brad Haines are pleased to announce an exclusive ... offer, valued at more than $300 per year, new patients can enjoy a lifetime ... a complimentary professional whitening procedure. , Stained or yellowed tooth enamel is common ...
(Date:8/23/2017)... , ... August 23, 2017 , ... Nightingale College continues ... Give Back Day is a time Nightingale College dedicates to serving and volunteering for ... thrive on donations and volunteers or those that need a little extra help. ...
(Date:8/23/2017)... (PRWEB) , ... August 23, 2017 , ... ... vans, announced today that has been named to the 2017 Inc. 500|5000, an ... based on a three-year growth rate of 139 percent, marking the twelfth year ...
(Date:8/23/2017)... ... August 23, 2017 , ... ... (SNAC) is holding an inaugural State of the Science Symposium in partnership ... Wednesday, Sept. 20, 2017. , This symposium provides a forum for global leaders ...
Breaking Medicine News(10 mins):
(Date:8/7/2017)... (NYSE: DPLO), the nation,s largest independent specialty pharmacy, announced financial ... unless otherwise noted, are to the quarter ended June 30, ... 2017 Highlights include: Revenue of $1,126 ... Total prescriptions dispensed of 220,000, compared to 241,000 ... Gross profit per prescription dispensed of $371, ...
(Date:8/4/2017)... , Aug. 4, 2017 The search ... shortly after a physician/patient consult has long been the ... was a notable focus of the largest meeting of ... according to healthcare market research firm Kalorama Information.  The ... testing (POCT) offerings or related supplies and software were ...
(Date:8/3/2017)... Aug. 3, 2017  Opioid addiction and other drugs ... healthcare costs and threatening outcomes, were problems taken on ... IVD industry that support them, met this week. This ... said that drugs of abuse, procalcitonin and acute kidney ... the organization,s 69th meeting in San Diego, ...
Breaking Medicine Technology: