Pharmacogenetic risk factors for osteonecrosis of the hip among children with leukemia

Mary V. Relling, Wenjian Yang, Soma Das, Edwin H. Cook, Gary L. Rosner, Michael Neel, Scott Howard, Raul Ribeiro, John T. Sandlund, Ching Hon Pui, Sue C. Kaste

Research output: Contribution to journalArticle

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Abstract

Purpose: One of the adverse effects of therapy for acute lymphoblastic leukemia (ALL) is osteonecrosis of the hip. Putative risk factors for osteonecrosis have included being female, white race, and older age. Our goal was to define possible genetic risk factors for osteonecrosis among children treated for newly diagnosed ALL. Methods: Using a candidate gene approach, we determined the genotypes for 16 common polymorphisms in genes likely to affect the pharmacokinetics or pharmacodynamics of antileukemic medications in 64 children with ALL. Therapy included glucocorticoids and antifolates. Magnetic resonance imaging of both hips was used to diagnose osteonecrosis, and was performed at similar times from the start of ALL therapy (P = .61 ) in the 25 patients with and the 39 patients without osteonecrosis (median, 447 days and 443 days, respectively). Results: In addition to age older than 10 years (odds ratio [OR], 24.2; P = .0001) and white race (OR, 11.1; P = .037), host factors for osteonecrosis included the vitamin D receptor Fokl start site CC genotype (OR, 4.5; P = .045), and the thymidylate synthase low activity 2/2 enhancer repeat genotype (OR, 7.4; P = .049). Conclusion: Because folate-related and vitamin D-receptor genetic variants have been associated with bone and vasculature morbidity, these pharmacogenetic associations likely reflect the interaction of antileukemic medications with germline sensitivity to drug actions, and might identify ALL patients at highest risk to develop osteonecrosis.

Original languageEnglish (US)
Pages (from-to)3930-3936
Number of pages7
JournalJournal of Clinical Oncology
Volume22
Issue number19
DOIs
StatePublished - Dec 1 2004

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Osteonecrosis
Pharmacogenetics
Hip
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Odds Ratio
Calcitriol Receptors
Genotype
Folic Acid Antagonists
Thymidylate Synthase
Folic Acid
Glucocorticoids
Genes
Therapeutics
Pharmacokinetics
Magnetic Resonance Imaging
Morbidity
Bone and Bones
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Relling, M. V., Yang, W., Das, S., Cook, E. H., Rosner, G. L., Neel, M., ... Kaste, S. C. (2004). Pharmacogenetic risk factors for osteonecrosis of the hip among children with leukemia. Journal of Clinical Oncology, 22(19), 3930-3936. https://doi.org/10.1200/JCO.2004.11.020

Pharmacogenetic risk factors for osteonecrosis of the hip among children with leukemia. / Relling, Mary V.; Yang, Wenjian; Das, Soma; Cook, Edwin H.; Rosner, Gary L.; Neel, Michael; Howard, Scott; Ribeiro, Raul; Sandlund, John T.; Pui, Ching Hon; Kaste, Sue C.

In: Journal of Clinical Oncology, Vol. 22, No. 19, 01.12.2004, p. 3930-3936.

Research output: Contribution to journalArticle

Relling, MV, Yang, W, Das, S, Cook, EH, Rosner, GL, Neel, M, Howard, S, Ribeiro, R, Sandlund, JT, Pui, CH & Kaste, SC 2004, 'Pharmacogenetic risk factors for osteonecrosis of the hip among children with leukemia', Journal of Clinical Oncology, vol. 22, no. 19, pp. 3930-3936. https://doi.org/10.1200/JCO.2004.11.020
Relling, Mary V. ; Yang, Wenjian ; Das, Soma ; Cook, Edwin H. ; Rosner, Gary L. ; Neel, Michael ; Howard, Scott ; Ribeiro, Raul ; Sandlund, John T. ; Pui, Ching Hon ; Kaste, Sue C. / Pharmacogenetic risk factors for osteonecrosis of the hip among children with leukemia. In: Journal of Clinical Oncology. 2004 ; Vol. 22, No. 19. pp. 3930-3936.
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