| The NQO1*2/*2 polymorphism is associated with poor overall survival in patients following resection of stages II and IIIa non-small cell lung cancer. | |
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MedLine Citation:
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PMID: 21479364 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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NAD(P)H:quinone oxidoreductase 1 (NQO1), is a cytosolic flavoenzyme that catalyzes the two-electron reduction of quinones into hydroquinones. A polymorphism (NQO1*2) alters enzymatic activity of NQO1 resulting in diminished NQO1 activity. Malignancies with NQO1*2 may be resistant to radiation and chemotherapy with resulting poorer survival. NQO1 allele was evaluated in subjects enrolled in ECOG 3590, a randomized comparison of radiation (RT) vs radiation and chemotherapy with cisplatin/etoposide (RCT) in patients with completely resected stages II and IIIa NSCLC. Overall survival was estimated using the Kaplan-Meier method and compared via the log-rank test. Cox models were used to assess the impact of covariates on outcomes. Among 152 patients with assessable samples, 24 (16%) had NQO1*2. Median follow-up was 139 months. The presence of NQO1*2/*2 was associated with decreased overall survival (OS) (median in the heterozygote/wild-type group 42.3 vs. 33.5 months in the variant group, p=0.04). In a multivariable Cox model, variant NQO1 (HR = 1.58, p = 0.05), age <60 (HR = 0.67, p = 0.04), PS 1 (HR = 1.47, p = 0.05), cardiovascular disease (HR = 1.93, p = 0.003) and alkaline phosphatase <100 mg/ml (HR = 0.59, p = 0.005) were all significant predictors of OS. NQO1*2/*2 may be an independent predictor of poor overall survival in individuals with resected stages II and IIIa NSCLC. Although the basis for the NQO1 association with decreased survival requires additional evaluation, NQO1 may represent a biomarker for guiding individualized therapy. |
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Authors:
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Jill M Kolesar; Suzanne E Dahlberg; Sharon Marsh; Howard L McLeod; David H Johnson; Steven M Keller; Joan H Schiller |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-04-06 |
Journal Detail:
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Title: Oncology reports Volume: 25 ISSN: 1791-2431 ISO Abbreviation: Oncol. Rep. Publication Date: 2011 Jun |
Date Detail:
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Created Date: 2011-04-19 Completed Date: 2011-08-08 Revised Date: 2012-09-18 |
Medline Journal Info:
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Nlm Unique ID: 9422756 Medline TA: Oncol Rep Country: Greece |
Other Details:
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Languages: eng Pagination: 1765-72 Citation Subset: IM |
Affiliation:
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School of Pharmacy, University of Wisconsin Paul P Carbone Comprehensive Cancer Center, University of Wisconsin, Madison, WI 53792-5669, USA. jmkolesar@pharmacy.wisc.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Combined Chemotherapy Protocols
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therapeutic use Carcinoma, Non-Small-Cell Lung / genetics*, mortality*, therapy Cisplatin / administration & dosage Combined Modality Therapy Etoposide / administration & dosage Female Genotype Humans Kaplan-Meier Estimate Lung Neoplasms / genetics*, mortality*, therapy Male NAD(P)H Dehydrogenase (Quinone) / genetics* Neoplasm Staging Polymorphism, Single Nucleotide* Proportional Hazards Models Radiotherapy Randomized Controlled Trials as Topic Tumor Markers, Biological / analysis, genetics |
| Grant Support | |
ID/Acronym/Agency:
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GM63340/GM/NIGMS NIH HHS; U01 GM063340-07/GM/NIGMS NIH HHS; U01 GM063340-08/GM/NIGMS NIH HHS; U01 GM063340-09/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Tumor Markers, Biological; 15663-27-1/Cisplatin; 33419-42-0/Etoposide; EC 1.6.5.2/NAD(P)H Dehydrogenase (Quinone); EC 1.6.5.2/NQO1 protein, human |
| Comments/Corrections | |
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