Significant effect of VEGFA polymorphisms on the clinical outcome of metastatic colorectal cancer patients treated with FOLFIRI-cetuximab

Author:

Rollin Jérôme12,Payancé Audrey123,Gouilleux-Gruart Valérie14,Boisdron-Celle Michelle5,Azzopardi Nicolas1,Morel Alain5,Gruel Yves12,Paintaud Gilles16,Gamelin Erick5,Watier Hervé14,Lecomte Thierry13

Affiliation:

1. CNRS, UMR 7292, GICC & Université Francois-Rabelais, Tours, France

2. CHRU de Tours, service d'Hématologie-Hémostase, Tours, France

3. CHRU de Tours, service d'Hépato-Gastroenterologie, Tours, France

4. CHRU de Tours, service d'Immunologie, Tours, France

5. INSERM U892 & service d'Oncopharmacologie et Pharmacogénétique, CRCNA, Angers, France

6. CHRU de Tours, service de Pharmacologie-Toxicologie, Tours, France

Abstract

Aim: The efficacy of a cetuximab-based regimen used to treat metastatic colorectal cancer (mCRC) could be influenced by VEGFA polymorphisms. Materials & methods: We studied the effects of five polymorphisms in the VEGFA gene (-2549D/I, -1154G/A, -460T/C, +405G/C and +936C/T) on the outcome of 98 mCRC patients treated with FOLFIRI plus cetuximab. Results: Patients homozygous for the -2549D, -1154G and -460T alleles did exhibit higher response rates to treatment and longer progression-free survival compared with others. In addition, the DGTGC and IGCGC haplotypes were significantly associated with a lower risk of disease progression. Conclusion: These findings suggest that VEGFA genetic variations might influence response/resistance of FOLFIRI plus cetuximab treatment in mCRC patients.

Publisher

Future Medicine Ltd

Subject

Pharmacology,Genetics,Molecular Medicine

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