An EZH2 polymorphism is associated with clinical outcome in metastatic colorectal cancer patients.
Ann Oncol
; 23(5): 1207-1213, 2012 May.
Article
in En
| MEDLINE
| ID: mdl-21926398
BACKGROUND: Despite therapeutic innovations, metastatic colorectal cancer (mCRC) is still characterized by poor prognosis and few molecular markers predict the risk of progression. Polycomb group genes (PcGs) are epigenetic modifiers involved in tumor suppressor gene silencing. PcG member EZH2 mediates gene silencing through histone-H3 lysine-27 methylation. In colorectal cancer (CRC), EZH2 overexpression predicts shorter survival. Recently, four EZH2 single-nucleotide polymorphisms (SNPs) have been described. The present study was aimed at evaluating the correlation between EZH2 SNPs and outcome parameters in mCRC patients. PATIENTS AND METHODS: DNA was extracted from blood samples of 110 mCRC patients treated with first-line 5-fluorouracil, folinic acid, irinotecan (FOLFIRI) and bevacizumab. Genotyping was carried out by real-time PCR. Genotype was used to predict objective response, progression-free survival (PFS) and overall survival (OS). EZH2 messenger RNA levels were evaluated on lymphocytes of a parallel cohort of 50 CRC patients. RESULTS: One allelic variant (rs3757441 C/C versus C/T or T/T) was significantly associated with shorter PFS and OS (P < 0.01 and P < 0.05, respectively). At multivariate analysis, the same variant resulted an independent predictor of PFS and OS (P < 0.05). The C/C variant was associated with significantly higher EZH2 expression (P < 0.05). CONCLUSION: An EZH2 SNP may be useful to predict clinical outcome in mCRC patients.
Full text:
1
Database:
MEDLINE
Main subject:
Transcription Factors
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Colorectal Neoplasms
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Adenocarcinoma
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Polymorphism, Single Nucleotide
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DNA-Binding Proteins
Type of study:
Evaluation_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limits:
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
Language:
En
Journal:
Ann Oncol
Journal subject:
NEOPLASIAS
Year:
2012
Type:
Article