Association of RRM1 -37A>C polymorphism with clinical outcome in colorectal cancer patients treated with gemcitabine-based chemotherapy.
Eur J Cancer
; 47(6): 839-47, 2011 Apr.
Article
en En
| MEDLINE
| ID: mdl-21220199
ABSTRACT
BACKGROUND:
To investigate whether single nucleotide polymorphisms (SNPs) in gemcitabine (GMB) metabolism genes were associated with clinical outcome in pre-treated metastatic colorectal cancer (mCRC) patients. PATIENTS ANDMETHODS:
SNPs of hCNT1, hENT1, CDA, dCTD and RRM1 genes were evaluated in 95 mCRC patients and detected using TaqMan genotyping assays. Association of genotypes with overall response rate (ORR), time to progression (TTP) and overall survival (OS) was tested by univariate and multivariate analysis. RRM1 -37A>C polymorphism was correlated with GMB IC50 value and with the RRM1 gene expression level in CRC cell lines.RESULTS:
The ORR was 38.9%. The median TTP and OS were 4 and 14.3 months, respectively. By multivariate analysis, patients carrying the RRM1 -37CC genotype or the CDA A-76 C-containing allele had a significantly higher likelihood of achieving a tumour response. RRM1 -37A>C polymorphism remained associated with clinical efficacy (TTP). In vitro experiments, in CRC cell lines, showed that the RRM1 A-37C genotype was associated with the levels of RRM1 expression and with GMB IC50 values. Finally, the down-regulation of RRM1 with a specific siRNA strongly influenced GMB sensitivity.CONCLUSION:
RRM1 -37A>C polymorphism may represent a useful biomarker to select mCRC patients most likely to benefit from GMB-based salvage therapy.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Polimorfismo Genético
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Neoplasias Colorrectales
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Proteínas Supresoras de Tumor
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Desoxicitidina
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Antimetabolitos Antineoplásicos
Tipo de estudio:
Observational_studies
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Risk_factors_studies
Límite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Eur J Cancer
Año:
2011
Tipo del documento:
Article
País de afiliación:
España