Document Detail


Polymorphism of the DNA repair enzyme XRCC1 is associated with treatment prediction in anthracycline and cyclophosphamide/methotrexate/5-fluorouracil-based chemotherapy of patients with primary invasive breast cancer.
MedLine Citation:
PMID:  17558308     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: Outcome and survival in anthracycline-based and cyclophosphamide/methotrexate/5-fluorouracil-based chemotherapy of invasive breast cancer are unpredictable. Insights into treatment prediction are expected from studies searching for an association between genetic polymorphisms and treatment outcome effects. A common feature of treatment with chemoreagents is therapeutically induced DNA damage. Therefore, we tested the hypothesis of a relationship between event-free survival and genotype distributions of seven polymorphic DNA repair enzymes and four cell cycle regulators. BASIC METHODS: This case-case comparison included 180 patients with primary invasive breast cancer diagnosed between 1986 and 2000 and subjected to adjuvant chemotherapy (anthracycline/cyclophosphamide or cyclophosphamide/methotrexate/5-fluorouracil). Ninety-two patients were reported without recurrence and 88 were reported with recurrences or dead. Median clinical follow-up was 61.7 months. Constitutional DNA isolated from archived tissues was genotyped at 19 loci by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Statistical analyses included adjusted risk estimates, Kaplan-Meier analyses, Cox proportional hazard model, and permutation testing. MAIN RESULTS: Carriers of the XRCC1_1196_AA genotype had a reduced risk for recurrence/death (odds ratio adjusted 0.19; 95% confidence interval: 0.06-0.61), which was observed in survival analyses of all patients (P=0.003) and patients treated with chemotherapy but not radiotherapy (P=0.006). Multivariate analysis confirmed XRCC1 as a potential treatment predictor (hazard ratio 0.62; 95% confidence interval: 0.43-0.89). The result was stable upon permutation testing. No other significant associations were observed. CONCLUSION: The DNA repair enzyme XRCC1 is a potential treatment predictor for the outcome and survival of anthracycline and cyclophosphamide/methotrexate/5-fluorouracil-based chemotherapy of invasive breast cancer.
Authors:
Malgorzata Jaremko; Christina Justenhoven; Werner Schroth; Benny K Abraham; Peter Fritz; Caren Vollmert; Thomas Illig; Wolfgang Simon; Matthias Schwab; Hiltrud Brauch
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Pharmacogenetics and genomics     Volume:  17     ISSN:  1744-6872     ISO Abbreviation:  Pharmacogenet. Genomics     Publication Date:  2007 Jul 
Date Detail:
Created Date:  2007-06-11     Completed Date:  2007-08-20     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101231005     Medline TA:  Pharmacogenet Genomics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  529-38     Citation Subset:  IM    
Affiliation:
Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, University of Tübingen, Stuttgart, Germany.
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MeSH Terms
Descriptor/Qualifier:
Anthracyclines / therapeutic use
Antineoplastic Agents / therapeutic use*
Breast Neoplasms / drug therapy*,  enzymology,  genetics*
Chemotherapy, Adjuvant
DNA Repair / genetics*
DNA-Binding Proteins / genetics*
Disease-Free Survival
Female
Fluorouracil / therapeutic use
Haplotypes
Humans
Methotrexate / therapeutic use
Pharmacogenetics
Polymorphism, Single Nucleotide
Retrospective Studies
Chemical
Reg. No./Substance:
0/Anthracyclines; 0/Antineoplastic Agents; 0/DNA-Binding Proteins; 0/X-ray repair cross complementing protein 1; 0/xeroderma pigmentosum group F protein; 51-21-8/Fluorouracil; 59-05-2/Methotrexate

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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