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 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.

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