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Genetic Variations Associated With Treatment Response for Childhood Leukaemia CHICAGO -- January 27, 2009 -- Children with acute lymphoblastic leukaemia (ALL) with certain genetic variations can have a different response to anticancer treatment than other patients, according to a study in the January 28 issue of JAMA. Jun J. Yang, PhD, St. Jude Children's Research Hospital, Memphis, Tennessee, and colleagues conducted a study to identify genetic factors that may affect treatment response in ALL. Researchers tested single nucleotide polymorphisms (SNPs) for their association with minimal residual disease (MRD) at the end of initial chemotherapy in 2 groups (N=487) of children treated for newly diagnosed ALL. Patients were enrolled between 1994 and 2006, with the last follow-up in 2006. The researchers found that there were 102 SNPs associated with MRD in both groups. All 102 SNPs remained significantly associated with MRD after adjustment for race, sex, leukocyte count at diagnosis, age, and ALL subtype. Of the 102 SNPs, 21 were significantly associated with haematologic relapse. In addition, 21 were associated with antileukaemic drug disposition, generally linking MRD eradication with greater drug exposure. The researchers found that 63 of 102 SNPs (61.7%) also were associated with early response, relapse risk, or antileukaemic drug disposition. "Although the acquired genetic characteristics of tumour cells play a critical role in drug responsiveness, our results show that inherited genetic variation of the patient also affects effectiveness of anticancer therapy, and that genome-wide approaches can identify novel and yet plausible pharmacogenetic variation," the authors concluded. "Such variation may be factored into treatment decisions in the future by placing additional emphasis on optimising drug delivery to overcome host genetic variation, in addition to the current emphasis on tumour genetic variation." SOURCE: JAMA E-mail this page to a friend or colleague! To print, use this version