@article{4a5f5db355e34d9db07623f84cb60096,
title = "Ancestry and pharmacogenomics of relapse in acute lymphoblastic leukemia",
abstract = "Although five-year survival rates for childhood acute lymphoblastic leukemia (ALL) are now over 80% in most industrialized countries1, not all children have benefited equally from this progress2. Ethnic differences in survival after childhood ALL have been reported in many clinical studies3-11, with poorer survival observed among African Americans or those with Hispanic ethnicity when compared with European Americans or Asians3-5. The causes of ethnic differences remain uncertain, although both genetic and non-genetic factors are likely important 4,12. Interrogating genome-wide germline SNP genotypes in an unselected large cohort of children with ALL, we observed that the component of genomic variation that co-segregated with Native American ancestry was associated with risk of relapse (P = 0.0029) even after adjusting for known prognostic factors (P = 0.017). Ancestry-related differences in relapse risk were abrogated by the addition of a single extra phase of chemotherapy, indicating that modifications to therapy can mitigate the ancestry-related risk of relapse.",
author = "Yang, {Jun J.} and Cheng Cheng and Meenakshi Devidas and Xueyuan Cao and Yiping Fan and Dario Campana and Wenjian Yang and Geoff Neale and Cox, {Nancy J.} and Paul Scheet and Borowitz, {Michael J.} and Winick, {Naomi J.} and Martin, {Paul L.} and Willman, {Cheryl L.} and Bowman, {W. Paul} and Camitta, {Bruce M.} and Andrew Carroll and Reaman, {Gregory H.} and Carroll, {William L.} and Mignon Loh and Hunger, {Stephen P.} and Pui, {Ching Hon} and Evans, {William E.} and Relling, {Mary V.}",
note = "Funding Information: We are indebted to all patients and their parents who participated in the St. Jude and COG protocols included in this study, the clinicians and research staff at the St. Jude and COG institutions and J. Pullen from the University of Mississippi at Jackson for assistance in classification of patients with ALL. Genome-wide genotyping of COG P9904/9905 samples was performed by the Center for Molecular Medicine with generous financial support from the Jeffrey Pride Foundation and the National Childhood Cancer Foundation. S.P.H. is the Ergen Family Chair in Pediatric Cancer, and J.J.Y. is supported by the American Society of Clinical Pharmacology and Therapeutics Young Investigator Award and Alex Lemonade Stand Foundation for Childhood Cancer Young Investigator Grant. We also thank M. Shriver at the Pennsylvania State University for sharing SNP genotype data of the Native American references. We are especially inspired by Damon Ingersoll, who bravely fought but lost his battle with ALL. This work was supported by the National Cancer Institute and National Institute of General Medical Sciences of the National Institutes of Health (grant numbers CA093552, CA78224, CA21765, R37CA36401, CA98543, CA114766, RC4CA156449, U10CA98413, U01GM 61393 and U01GM 92666), American Lebanese Syrian Associated Charities (ALSAC) and CureSearch.",
year = "2011",
month = mar,
doi = "10.1038/ng.763",
language = "English",
volume = "43",
pages = "237--241",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "3",
}