Significant Effect of VEGFA Polymorphisms on the Clinical Outcome of Metastatic Colorectal Cancer Patients Treated with FOLFIRI-Cetuximab

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.

Keywords::

• biomarkers
• cetuximab
• colorectal cancer
• SNPs
• VEGFA

Acknowledgements

The authors would like to thank the Investigators who included patients in the study: O Capitain, J-P Metges, A Adenis, J-L Raoul, Y Heng Lam, R Faroux, C Masliah and V Berger. The authors also thank M-N Marsson for her help in the genotyping of VEGFA. Genotyping was carried out within the CePiBAc platform.

Financial & competing interests disclosure

CePiBAc is funded by the EU and the region Centre. This work received funding in the form of Research Program grants from the Cancéropôle Grand-Ouest, from the French National Society of Gastroenterology, and from la Ligue contre le Cancer. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

CePiBAc is funded by the EU and the region Centre. This work received funding in the form of Research Program grants from the Cancéropôle Grand-Ouest, from the French National Society of Gastroenterology, and from la Ligue contre le Cancer. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.