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The value of XPD and XRCC1 genotype polymorphisms to predict clinical outcome in metastatic colorectal carcinoma patients with irinotecan-based regimens

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Abstract

Background

Previous studies have suggested that DNA repair enzyme polymorphisms may bear prognostic value in metastatic colorectal carcinoma (MCRC).

Methods

We prospectively treated 43 MCRC patients with irinotecan-based regimens (XELIRI or IFL). Allelic variants of the XRCC1 gene at codon 399 and XPD gene at codon 751 were analyzed in lymphocyte DNA by PCR–RFLP. Clinical outcome variables: overall survival (OAS), progression-free survival (PFS) and the occurrence of grade 3 or 4 hematological and gastrointestinal (GIS) toxicities were evaluated.

Results

In the univariate analysis for OAS (n = 43) only XPD and XRCC1 polymorphisms were significant (P = 0.05 and P = 0.04, respectively). After adjustment for performance status (ECOG = 0, 1 vs. 2) and disease extent (single vs. multiple metastatic site), XRCC1 genotype and performance status retained significance (HR = 2.85, P = 0.04, and HR = 3.19, P = 0.02, respectively). Gln/Gln genotype was associated with the greatest risk of death. Type of presentation (metastatic vs. local disease at first presentation) was the only significant predictor of PFS in the univariate analysis (n = 40, P = 0.003). After adjustment for performance status and disease extent, type of presentation retained its significance (HR = 4.35, P = 0.003). None of the toxicities was associated with these genotypes.

Conclusions

XRCC1 genotype independently predicted overall survival in metastatic colorectal carcinoma patients treated with irinotecan-based chemotherapy.

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Conflict of interest statement

There are no financial disclosures from any of the authors.

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Authors and Affiliations

  1. Department of Medical Oncology, Meram Medical Faculty, Selcuk University, Meram, 42080, Konya, Turkey

    Mehmet Artac

  2. Department of Medical Oncology, Medical Faculty, Akdeniz University, Antalya, Turkey

    Hakan Bozcuk, Mustafa Ozdogan & Burhan Savas

  3. Department of Medical Biology, Medical Faculty, Gaziantep University, Gaziantep, Turkey

    Sacide Pehlivan & Tugce Sever

  4. Department of Internal Medicine, Medical Faculty, Akdeniz University, Antalya, Turkey

    Songül Akcan

  5. Department of Hematology, Medical Faculty, Gaziantep University, Gaziantep, Turkey

    Mustafa Pehlivan

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  1. Mehmet Artac
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  2. Hakan Bozcuk
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  3. Sacide Pehlivan
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  4. Songül Akcan
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  5. Mustafa Pehlivan
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  6. Tugce Sever
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  7. Mustafa Ozdogan
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  8. Burhan Savas
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Correspondence to Mehmet Artac.

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Artac, M., Bozcuk, H., Pehlivan, S. et al. The value of XPD and XRCC1 genotype polymorphisms to predict clinical outcome in metastatic colorectal carcinoma patients with irinotecan-based regimens. J Cancer Res Clin Oncol 136, 803–809 (2010). https://doi.org/10.1007/s00432-009-0720-3

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  • DOI: https://doi.org/10.1007/s00432-009-0720-3

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