Featured Research

from universities, journals, and other organizations

Native American ancestry linked to greater risk of relapse in young leukemia patients

Date:
February 6, 2011
Source:
St. Jude Children's Research Hospital
Summary:
The first genome-wide study to demonstrate an inherited genetic basis for racial and ethnic disparities in cancer survival linked Native American ancestry with an increased risk of relapse in young leukemia patients.

The first genome-wide study to demonstrate an inherited genetic basis for racial and ethnic disparities in cancer survival linked Native American ancestry with an increased risk of relapse in young leukemia patients. The work was done by investigators at St. Jude Children's Research Hospital and the Children's Oncology Group (COG).

Along with identifying Native American ancestry as a potential new marker of poor treatment outcome, researchers reported evidence the added risk could be eliminated by administering an extra phase of chemotherapy. The study involved 2,534 children and adolescents battling acute lymphoblastic leukemia (ALL), the most common childhood cancer. The work appears in the February 6 advance online edition of the scientific journal Nature Genetics.

The children were all treated in protocols conducted by St. Jude or COG. Although the overall cure rate for childhood ALL now tops 80 percent, and is close to 90 percent at St. Jude, racial and ethnic disparities have persisted. Based on self-declared status, African-American and Hispanic children with the disease have often fared worse than their white and Asian counterparts. This is the first study to use genomics to define ancestry, rather than relying on self-declared racial or ethnic categories.

"To overcome racial disparity you have to understand the reasons behind it," said Jun Yang, Ph.D., St. Jude Department of Pharmaceutical Sciences assistant member and the study's first author. "While genetic ancestry may not completely explain the racial differences in relapse risk or response to treatment, this study clearly shows for the first time that it is a very important contributing factor."

This study identified a possible mechanism linking ancestry and relapse. Hispanic patients, who have a high percentage of Native American ancestry, were more likely than other patients to carry a version of the PDE4B gene that was also strongly associated with relapse. The PDE4B variants were also linked with reduced sensitivity to glucocorticoids, medications that play a key role in ALL treatment. "This is just one example of how ancestry could affect relapse risk," said the study's senior author Mary Relling, Pharm.D., St. Jude Pharmaceutical Sciences chair. "It is likely that many other genes are involved."

Investigators also found ALL patients with greater Native American ancestry who received additional chemotherapy as part of a COG clinical trial benefited more from the extra treatment than other children. "These are important steps on the way to personalized cancer care, whereby treatment can be tailored to provide maximal benefit to patient subgroups, and someday, individual patients," said co-author Stephen Hunger, M.D., University of Colorado professor of pediatrics and chair of COG's ALL committee.

For this study, scientists used a library of 444,044 common genetic variations known as single nucleotide polymorphisms, or SNPs, to search each patient's DNA for evidence linking ancestry and relapse. The study found that cancer was 59 percent more likely to return in patients whose genetic makeup reflected at least 10 percent Native American ancestry.

About 25 percent of patients in this study met the 10 percent threshold. The percentage was highest among the self-reported Hispanic and Native American patients, who have been reported to be at higher risk of relapse.

Native American ancestry identified patients at high risk of relapse missed by current clinical tools, including testing for minimal residual disease (MRD), which measures the cancer cells that survive the initial round of therapy. Relling said additional research is needed to confirm the findings before screening becomes part of clinical care.

This study used advances in high throughput genomic technologies to better understand why cancer treatment sometimes fails and how the failure is related to genetic ancestry. Unlike previous research that relied on patient self-reports of race and ethnicity and focused on specific populations, this study focused on a group of patients as diverse as the U.S. and representative of the nation's entire ALL population.

The other authors on this paper are Cheng Cheng, Xueyuan Cao, Yiping Fan, Dario Campana, Wenjian Yang, Geoff Neale, Ching-Hon Pui and William E. Evans, all of St. Jude; Meenakshi Devidas, University of Florida; Nancy Cox, University of Chicago; Paul Scheet, University of Texas M.D. Anderson Cancer Center; Michael Borowitz, Johns Hopkins Medical Institute; Naomi Winick, University of Texas Southwestern Medical Center; Paul Martin, Duke University; Cheryl Willman, University of New Mexico Cancer Center; W. Paul Bowman, Cook Children's Medical Center; Bruce Camitta, Medical College of Wisconsin; Andrew Carroll, University of Alabama at Birmingham; Gregory Reaman, Children's National Medical Center; William Carroll, New York University Cancer Institute and Mignon Loh, University of California at San Francisco.

The work was supported in part by National Institutes of Health's National Cancer Institute, National Institute of General Medical Sciences and National Institute of Child Health and Human Development as well as the Jeffrey Pride Foundation, National Childhood Cancer Foundation, CureSearch and ALSAC.


Story Source:

The above story is based on materials provided by St. Jude Children's Research Hospital. Note: Materials may be edited for content and length.


Journal Reference:

  1. Jun J Yang, Cheng Cheng, Meenakshi Devidas, Xueyuan Cao, Yiping Fan, Dario Campana, Wenjian Yang, Geoff Neale, Nancy J Cox, Paul Scheet, Michael J Borowitz, Naomi J Winick, Paul L Martin, Cheryl L Willman, W Paul Bowman, Bruce M Camitta, Andrew Carroll, Gregory H Reaman, William L Carroll, Mignon Loh, Stephen P Hunger, Ching-Hon Pui, William E Evans, Mary V Relling. Ancestry and pharmacogenomics of relapse in acute lymphoblastic leukemia. Nature Genetics, 2011; DOI: 10.1038/ng.763

Cite This Page:

St. Jude Children's Research Hospital. "Native American ancestry linked to greater risk of relapse in young leukemia patients." ScienceDaily. ScienceDaily, 6 February 2011. <www.sciencedaily.com/releases/2011/02/110206132908.htm>.
St. Jude Children's Research Hospital. (2011, February 6). Native American ancestry linked to greater risk of relapse in young leukemia patients. ScienceDaily. Retrieved July 25, 2014 from www.sciencedaily.com/releases/2011/02/110206132908.htm
St. Jude Children's Research Hospital. "Native American ancestry linked to greater risk of relapse in young leukemia patients." ScienceDaily. www.sciencedaily.com/releases/2011/02/110206132908.htm (accessed July 25, 2014).

Share This




More Health & Medicine News

Friday, July 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

New Painkiller Designed To Discourage Abuse: Will It Work?

New Painkiller Designed To Discourage Abuse: Will It Work?

Newsy (July 24, 2014) The FDA approved Targiniq ER on Wednesday, a painkiller designed to keep users from abusing it. Like any new medication, however, it has doubters. Video provided by Newsy
Powered by NewsLook.com
Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Newsy (July 24, 2014) Sheik Umar Khan has treated many of the people infected in the Ebola outbreak, and now he's become one of them. Video provided by Newsy
Powered by NewsLook.com
Condemned Man's US Execution Takes Nearly Two Hours

Condemned Man's US Execution Takes Nearly Two Hours

AFP (July 24, 2014) America's death penalty debate raged Thursday after it took nearly two hours for Arizona to execute a prisoner who lost a Supreme Court battle challenging the experimental lethal drug cocktail. Duration: 00:55 Video provided by AFP
Powered by NewsLook.com
Can Watching TV Make You Feel Like A Failure?

Can Watching TV Make You Feel Like A Failure?

Newsy (July 24, 2014) A study by German researchers claims watching TV while you're stressed out can make you feel guilty and like a failure. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

    Health News

      Environment News

        Technology News



          Save/Print:
          Share:

          Free Subscriptions


          Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

          Get Social & Mobile


          Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

          Have Feedback?


          Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
          Mobile: iPhone Android Web
          Follow: Facebook Twitter Google+
          Subscribe: RSS Feeds Email Newsletters
          Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins