当前位置： SCI文献检索 > AMERICAN JOURNAL OF HEMATOLOGY期刊下所有文献 > Genetic polymorphisms in oxidative stress-related genes are associated with outcomes following treatment for aggressive B-cell non-Hodgkin lymphoma.

Genetic polymorphisms in oxidative stress-related genes are associated with outcomes following treatment for aggressive B-cell non-Hodgkin lymphoma.

Abstract：

: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 MPO rs2243828 (hazard ratio [HR] = 1.87, 95% confidence interval [CI] = 1.14-3.06, P = 0.013), AKR1C3 rs10508293 (HR = 2.09, 95% CI = 1.28-3.41, P = 0.0032) and NCF4 rs1883112 (HR = 0.66, 95% CI = 0.43-1.02, P = 0.06). The association of the NCF4 SNP with PFS was replicated in the validation dataset (HR = 0.66, 95% CI = 0.44-1.01, P = 0.05) and the meta-analysis was significant (HR = 0.66, 95% CI = 0.49-0.89, P < 0.01). The association of the MPO 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 NCF4, HR = 0.72, 95% CI = 0.51-1.02, P = 0.07 and for MPO, HR = 2.06, 95% CI = 1.36-3.12, P < 0.01). In addition, patients with the rare homozygote of the NCF4 SNP had an increased risk of hematologic toxicity. We concluded that genetic variations in NCF4 may contribute to treatment outcomes for patients with aggressive NHL.

journal_name

Am J Hematol

journal_title

American journal of hematology

authors

Gustafson HL,Yao S,Goldman BH,Lee K,Spier CM,LeBlanc ML,Rimsza LM,Cerhan JR,Habermann TM,Link BK,Maurer MJ,Slager SL,Persky DO,Miller TP,Fisher RI,Ambrosone CB,Briehl MM

doi

10.1002/ajh.23709

subject

Has Abstract

pub_date

2014-06-01 00:00:00

pages

639-45

issue

eissn

0361-8609

issn

1096-8652

journal_volume

pub_type

杂志文章

在线工具

Genetic polymorphisms in oxidative stress-related genes are associated with outcomes following treatment for aggressive B-cell non-Hodgkin lymphoma.