Genetics Linked to Variations in Treatment Response-- Lisa Cockrell, PhD
Tuesday, January 27, 2009
TUESDAY, Jan. 27 (HealthDay News) -- Genetic variations among patients may explain differences in treatment responses for pediatric acute lymphoblastic leukemia (ALL), according to research published Jan. 28 in the Journal of the American Medical Association.
Jun J. Yang, Ph.D., of St. Jude Children's Research Hospital in Memphis, Tenn., and colleagues performed a genome-wide interrogation of 476,796 single nucleotide polymorphisms (SNPs) to explore the association between individual genetic variability and response to ALL therapy. Genotypes associated with risk of minimal residual disease at the end of induction therapy were identified among two independent cohorts of 487 children with newly diagnosed ALL.
The investigators identified 102 SNPs from both cohorts associated with a median minimal residual disease risk of 2.18-fold. Over half (63 SNPs) were linked to early response, relapse or drug disposition. For example, 21 SNPs were significantly associated with risk of hematologic relapse, and 21 SNPs were linked to anti-leukemia drug pharmacokinetics. The report also notes that five SNPs were located in the IL15 gene, and these were associated with an increased risk of minimal residual disease.
"Although the acquired genetic characteristics of tumor cells play a critical role in drug responsiveness, our results show that inherited genetic variation of the patient also affects effectiveness of anti-cancer therapy, and that genome-wide approaches can identify novel and yet plausible pharmacogenetic variation," the authors state.
Several of the study authors report financial relationships with the pharmaceutical industry.
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