Polymorphisms in the ABCB1 gene and effect on outcome and toxicity in childhood acute lymphoblastic leukemia
2015 (English)In: The Pharmacogenomics Journal, ISSN 1470-269X, E-ISSN 1473-1150, Vol. 15, no 4, 372-379 p.Article in journal (Refereed) Published
The membrane transporter P-glycoprotein, encoded by the ABCB1 gene, influences the pharmacokinetics of anti-cancer drugs. We hypothesized that variants of ABCB1 affect outcome and toxicity in childhood acute lymphoblastic leukemia (ALL). We studied 522 Danish children with ALL, 93% of all those eligible. Risk of relapse was increased 2.9-fold for patients with the 1199GA variant versus 1199GG (P = 0.001), and reduced 61% and 40%, respectively, for patients with the 3435CT or 3435TT variants versus 3435CC (overall P = 0.02). The degree of bone marrow toxicity during doxorubicin, vincristine and prednisolone induction therapy was more prominent in patients with 3435TT variant versus 3435CT/3435CC (P = 0.01/P less than 0.0001). We observed more liver toxicity after high-dose methotrexate in patients with 3435CC variant versus 3435CT/TT ( P = 0.03). In conclusion, there is a statistically significant association between ABCB1 polymorphisms, efficacy and toxicity in the treatment of ALL, and ABCB1 1199G greater than A may be a new possible predictive marker for outcome in childhood ALL.
Place, publisher, year, edition, pages
Nature Publishing Group: Open Access Hybrid Model Option B , 2015. Vol. 15, no 4, 372-379 p.
Clinical Medicine Hematology
IdentifiersURN: urn:nbn:se:liu:diva-120735DOI: 10.1038/tpj.2014.81ISI: 000358448500012PubMedID: 25582575OAI: oai:DiVA.org:liu-120735DiVA: diva2:848221
Funding Agencies|Swedish Cancer Society; Swedish Research Council; County Concil in Ostergotland; Danish Childhood Cancer Foundation; University Hospital Rigshospitalet, Denmark2015-08-242015-08-242016-04-12