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An EZH2 polymorphism is associated with clinical outcome in metastatic colorectal cancer patients

  1. Author:
    Crea, F.
    Fornaro, L.
    Paolicchi, E.
    Masi, G.
    Frumento, P.
    Loupakis, F.
    Salvatore, L.
    Cremolini, C.
    Schirripa, M.
    Graziano, F.
    Ronzoni, M.
    Ricci, V.
    Farrar, W. L.
    Falcone, A.
    Danesi, R.

  2. Author Address

    [Crea, F.; Paolicchi, E.; Danesi, R.] Univ Pisa, Div Pharmacol, Dept Internal Med, I-56126 Pisa, Italy. [Fornaro, L.; Masi, G.; Loupakis, F.; Salvatore, L.; Cremolini, C.; Schirripa, M.; Falcone, A.] Univ Pisa, Div Med Oncol, Dept Oncol Transplants & New Technol Med, I-56126 Pisa, Italy. [Frumento, P.] Karolinska Inst, Inst Environm Hlth, Unit Biostat, Stockholm, Sweden. [Ronzoni, M.; Ricci, V.] Ist Sci San Raffaele, Div Med Oncol, I-20132 Milan, Italy. [Farrar, W. L.] Natl Inst Canc Frederick, Lab Canc Prevent, Canc Stem Cell Sect, Frederick, MD USA.;Crea, F (reprint author), Univ Pisa, Div Pharmacol, Dept Internal Med, Via Roma 67, I-56126 Pisa, Italy;fr.crea@gmail.com
    1. Year: 2012
    2. Date: May
    3. Epub Date: 2019 12 04
  2. Journal: Annals of Oncology
    1. 23
    2. 5
    3. Pages: 1207-1213
  4. Type of Article: Article
  5. ISSN: 0923-7534
  1. Abstract:

    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. 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. 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). An EZH2 SNP may be useful to predict clinical outcome in mCRC patients.

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  2. DOI: 10.1093/annonc/mdr387
  3. PMID: 32018578
  4. View record in Web of Science®
  5. WOS: 000303336400018

Library Notes

  1. Fiscal Year: FY2011-2012
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