Ancestry and pharmacogenomics of relapse in acute lymphoblastic leukemia.

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 MV
Nat Genet. 2011 43 (3): 237-41

PMID: 21297632 · PMCID: PMC3104508 · DOI:10.1038/ng.763

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.

MeSH Terms (17)

African Americans Asian Continental Ancestry Group Child Child, Preschool Ethnic Groups Female Hispanic Americans Humans Indians, North American Male Pharmacogenetics Polymorphism, Single Nucleotide Precursor Cell Lymphoblastic Leukemia-Lymphoma Principal Component Analysis Recurrence Risk Survival Rate

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