Journal article
Genetic polymorphisms in oxidative stress related genes are associated with outcomes following treatment for aggressive B-cell non-Hodgkin lymphoma
American journal of hematology, Vol.89(6), pp.639-645
06/2014
DOI: 10.1002/ajh.23709
PMCID: PMC4137041
PMID: 24633940
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 3 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.
Details
- Title: Subtitle
- Genetic polymorphisms in oxidative stress related genes are associated with outcomes following treatment for aggressive B-cell non-Hodgkin lymphoma
- Creators
- Heather L Gustafson - Cancer Biology Graduate Interdisciplinary Program, University of Arizona, Tucson, AZSong Yao - Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NYJames R Cerhan - Department of Health Sciences Research, Mayo Clinic, Rochester, MNBryan H Goldman - Southwest Oncology Group Statistical Center, Fred Hutchinson Cancer Center, Seattle, WABrian K Link - Department of Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, IAKristy Lee - Cancer Biology Graduate Interdisciplinary Program, University of Arizona, Tucson, AZCatherine M Spier - Department of Pathology, University of Arizona, Tucson, AZMichael L LeBlanc - Southwest Oncology Group Statistical Center, Fred Hutchinson Cancer Center, Seattle, WALisa M Rimsza - Department of Pathology, University of Arizona, Tucson, AZThomas M Habermann - Department of Health Sciences Research, Mayo Clinic, Rochester, MNMatthew J Maurer - Department of Health Sciences Research, Mayo Clinic, Rochester, MNSusan L Slager - Department of Health Sciences Research, Mayo Clinic, Rochester, MNDaniel O Persky - Arizona Cancer Center, University of Arizona, Tucson, AZThomas P Miller - Arizona Cancer Center, University of Arizona, Tucson, AZRichard I Fisher - Fox Chase Cancer Center, Philadelphia, PAChristine B Ambrosone - Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NYMargaret M Briehl - Department of Pathology, University of Arizona, Tucson, AZ
- Resource Type
- Journal article
- Publication Details
- American journal of hematology, Vol.89(6), pp.639-645
- DOI
- 10.1002/ajh.23709
- PMID
- 24633940
- PMCID
- PMC4137041
- ISSN
- 0361-8609
- eISSN
- 1096-8652
- Language
- English
- Date published
- 06/2014
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Epidemiology; Internal Medicine
- Record Identifier
- 9984094328202771
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