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

Jérôme Rollin (1, 2) , Audrey Payancé (1, 2) , Valérie Gouilleux-Gruart (1, 2) , Michelle Boisdron-Celle (3) , Nicolas Azzopardi (1) , Alain Morel (3) , Yves Gruel (1, 2) , Gilles Paintaud (1, 2) , Erick Gamelin (3) , Herve Watier (1, 2) , Thierry Lecomte (1, 2)

1 GICC UMR 7292 CNRS - Génétique, immunothérapie, chimie et cancer (GICC), UMR 7292 CNRS [2012-2017]
2 CHRU Tours - Centre Hospitalier Régional Universitaire de Tours
3 CRCNA - Centre de Recherche en Cancérologie Nantes-Angers

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.

Keywords: biomarkers; cetuximab; colorectal cancer; SNPs; VEGFA

Domains: Life Sciences [q-bio]; Pharmaceutical sciences; Medication; Life Sciences [q-bio]; Pharmaceutical sciences; Pharmacology; Life Sciences [q-bio]; Immunology; Immunotherapy; Life Sciences [q-bio]; Cancer

Jérôme Rollin, Audrey Payancé, Valérie Gouilleux-Gruart, Michelle Boisdron-Celle, Nicolas Azzopardi, et al.. Significant effect of VEGFA polymorphisms on the clinical outcome of metastatic colorectal cancer patients treated with FOLFIRI-cetuximab. Pharmacogenomics, 2015, 16 (18), pp.2035-2043. ⟨10.2217/pgs.15.139⟩. ⟨hal-02381189⟩