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 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.
authors.affiliation: Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: Jun J
authors.initials: JJ
authors.lastname: Yang
authors.forename: Cheng
authors.initials: C
authors.lastname: Cheng
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Devidas
authors.forename: Xueyuan
authors.initials: X
authors.lastname: Cao
authors.forename: Yiping
authors.initials: Y
authors.lastname: Fan
authors.forename: Dario
authors.initials: D
authors.lastname: Campana
authors.forename: Wenjian
authors.initials: W
authors.lastname: Yang
authors.forename: Geoff
authors.initials: G
authors.lastname: Neale
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Cox
authors.forename: Paul
authors.initials: P
authors.lastname: Scheet
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Borowitz
authors.forename: Naomi J
authors.initials: NJ
authors.lastname: Winick
authors.forename: Paul L
authors.initials: PL
authors.lastname: Martin
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Willman
authors.forename: W Paul
authors.initials: WP
authors.lastname: Bowman
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Camitta
authors.forename: Andrew
authors.initials: A
authors.lastname: Carroll
authors.forename: Gregory H
authors.initials: GH
authors.lastname: Reaman
authors.forename: William L
authors.initials: WL
authors.lastname: Carroll
authors.forename: Mignon
authors.initials: M
authors.lastname: Loh
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Hunger
authors.forename: Ching-Hon
authors.initials: CH
authors.lastname: Pui
authors.forename: William E
authors.initials: WE
authors.lastname: Evans
authors.forename: Mary V
authors.initials: MV
authors.lastname: Relling
mesh_terms: D001741:Black or African American; D044466:Asian People; D002648:Child; D002675:Child, Preschool; D005006:Ethnicity / Q000235:genetics; D005260:Female; D006630:Hispanic or Latino; D006801:Humans; D007198:Indians, North American; D008297:Male; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000208:ethnology / Q000235:genetics* / Q000628:therapy; D025341:Principal Component Analysis; D012008:Recurrence; D012306:Risk; D015996:Survival Rate