Genetic polymorphisms in oxidative stress‐related genes are associated with outcomes following treatment for aggressive B‐cell non‐Hodgkin lymphoma. Issue 6 (12th April 2014)

• Record Type: Journal Article
• Authors: Gustafson, Heather L.; Yao, Song; Goldman, Bryan H.; Lee, Kristy; Spier, Catherine M.; LeBlanc, Michael L.; Rimsza, Lisa M.; Cerhan, James R.; Habermann, Thomas M.; Link, Brian K.; Maurer, Matthew J.; Slager, Susan L.; Persky, Daniel O.; Miller, Thomas P.; Fisher, Richard I.; Ambrosone, Christine B.; Briehl, Margaret M.
• Is Part Of: American journal of hematology. Volume 89:Issue 6(2014:Jun.)
• Page Start: 639
• Page End: 645
• Publication Date: 2014-04-12
• Subjects: Hematology -- Periodicals; 616.15
• DOI: 10.1002/ajh.23709
• Languages: English
• ISSNs: 0361-8609

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Variable survival outcomes are seen following treatment for aggressive non‐Hodgkin lymphoma (NHL). This study examined whether outcomes for aggressive B‐cell NHL are associated with single nucleotide polymorphisms (SNPs) in oxidative stress‐related genes, which can alter drug metabolism and immune responses. Genotypes for 53 SNPs in 29 genes were determined for 337 patients given anthracycline‐based therapies. Their associations with progression‐free survival (PFS) and overall survival (OS) were estimated by Cox proportional hazard regression; associations with hematologic toxicity were estimated by logistic regression. To validate the findings, the top three SNPs were tested in an independent cohort of 572 DLBCL patients. The top SNPs associated with PFS in the discovery cohort were the rare homozygotes for <italic>MPO</italic> rs2243828 (hazard ratio [HR] = 1.87, 95% confidence interval [CI] = 1.14–3.06, <italic>P</italic> = 0.013), <italic>AKR1C3</italic> rs10508293 (HR = 2.09, 95% CI = 1.28–3.41, <italic>P</italic> = 0.0032) and <italic>NCF4</italic> rs1883112 (HR = 0.66, 95% CI = 0.43–1.02, <italic>P</italic> = 0.06). The association of the <italic>NCF4</italic> SNP with PFS was replicated in the validation dataset (HR = 0.66, 95% CI = 0.44–1.01, <italic>P</italic> = 0.05) and the meta‐analysis was significant (HR = 0.66, 95% CI = 0.49–0.89, <italic>P</italic> < 0.01). The association of the <italic>MPO</italic> SNP was attenuated in the validation dataset, while the meta‐analysis remained significant (HR = 1.64, 95% CI = 1.12–2.41). These two SNPs showed similar trends with OS in the meta‐analysis (for <italic>NCF4</italic>, HR = 0.72, 95% CI = 0.51–1.02, <italic>P</italic> = 0.07 and for <italic>MPO</italic>, HR = 2.06, 95% CI = 1.36–3.12, <italic>P</italic> < 0.01). In addition, patients with the rare homozygote of the <italic>NCF4</italic> SNP had an increased risk of hematologic toxicity. We concluded that genetic variations in <italic>NCF4</italic> may contribute to treatment outcomes for patients with aggressive NHL. Am. J. Hematol. 89:639–645, 2014. © 2014 Wiley Periodicals, Inc.</p> </abstract>