Ancestry and pharmacogenomics of relapse in acute lymphoblastic leukemia. Nat Genet 2011 Mar;43(3):237-41
Date
02/08/2011Pubmed ID
21297632Pubmed Central ID
PMC3104508DOI
10.1038/ng.763Scopus ID
2-s2.0-79952188025 (requires institutional sign-in at Scopus site) 232 CitationsAbstract
Although five-year survival rates for childhood acute lymphoblastic leukemia (ALL) are now over 80% in most industrialized countries, not all children have benefited equally from this progress. Ethnic differences in survival after childhood ALL have been reported in many clinical studies, with poorer survival observed among African Americans or those with Hispanic ethnicity when compared with European Americans or Asians. The causes of ethnic differences remain uncertain, although both genetic and non-genetic factors are likely important. 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 List
Yang JJ, Cheng C, Devidas M, Cao X, Fan Y, Campana D, Yang W, Neale G, Cox NJ, Scheet P, Borowitz MJ, Winick NJ, Martin PL, Willman CL, Bowman WP, Camitta BM, Carroll A, Reaman GH, Carroll WL, Loh M, Hunger SP, Pui CH, Evans WE, Relling MVMESH terms used to index this publication - Major topics in bold
ChildChild, Preschool
Female
Humans
Indians, North American
Male
Pharmacogenetics
Polymorphism, Single Nucleotide
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Principal Component Analysis
Recurrence
Risk
Survival Rate
