Affiliations: [a] Third Department of Medical Oncology, General Oncology Hospital of Kifissia ``AgioiAnargyroi'', Athens, Greece | [b] First Department of Propaedeutic Surgery, School of Medicine, University of Athens, Athens, Greece | [c] Department of Basic Medical Sciences, Laboratory of Biology, School of Medicine, University of Athens, Athens, Greece | [d] Second Department of Internal Medicine, School of Medicine, University of Athens, Athens, Greece
Correspondence:
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Corresponding author: Maria Gazouli, Department of Basic Medical Science, Laboratory of Biology, School of Medicine, University of Athens, Michalakopoulou 176, 11725 Athens, Greece. Tel.: +30 21 07462231; Fax: +30 21 07462231; E-mail:[email protected]
Abstract:
BACKGROUND: Bevacizumab, an angiogenesis inhibitor is used in
regimens for metastatic colorectal cancer (CRC). A minority of cancer cells
with characteristics of cancer stem cells (CSC) may be responsible for
progression and development of chemotherapy resistance in this disease.
CD133 is a well-known CSC marker and is associated with angiogenesis, poor
prognosis and resistance to chemotherapy. OBJECTIVE: The purpose of our study was to evaluate the association
between the rs3130 and rs2286455 polymorphisms of the CD133 gene and the
response, toxicity, and overall survival of patients with CRC on
bevacizumab-based treatment. METHODS: Forty-three patients receiving bevacizumab, irinotecan and
capecitabine and 15 patients receiving bevacizumab, irinotecan and 5-FU were
included. Efficacy and toxicity were evaluated. KRAS mutation analysis and
rs3130 and rs2286455 polymorphisms genotyping in the tumors and peripheral
blood respectively were performed with PCR-RFLP. RESULTS: No association between KRAS mutated alleles and response
was found. The rs3130 CC genotype was associated with reduced toxicity of
treatments (p= 0.0017), and with lower overall survival on bevacizumab
(p= 0.002). CONCLUSIONS: The CC genotype of rs3130 polymorphism in the CD133 gene can predict poorer overall survival in patients with metastatic CRC on bevacizumab which cannot
be attributed to increased treatment toxicity.
