Ancestry and pharmacogenomics of relapse in acute lymphoblastic leukemia


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.

DOI: 10.1038/ng.763

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@article{Yang2011AncestryAP, title={Ancestry and pharmacogenomics of relapse in acute lymphoblastic leukemia}, author={Jun J. Yang and Cheng Cheng and Meenakshi Devidas and Xueyuan Cao and Yiping Fan and Dario Campana and Wenjian Yang and Geoff A. Neale and Nancy J. Cox and Paul Scheet and Michael J. Borowitz and Naomi Joan Winick and P. L. Mart{\'i}n and Cheryl Willman and William Paul Bowman and Bruce M. Camitta and Andrew A Carroll and Gregory H. Reaman and William L. Carroll and Mignon L Loh and Stephen P Hunger and Ching-Hon Pui and William E. Evans and Mary V Relling}, journal={Nature Genetics}, year={2011}, volume={43}, pages={237-241} }