Association between bevacizumab-related hypertension and vascular endothelial growth factor (VEGF) gene polymorphisms in Japanese patients with metastatic colorectal cancer
- 476 Downloads
Bevacizumab, a monoclonal antibody that binds to VEGF, has a well-known toxic effect of hypertension. We studied possible associations between bevacizumab-related hypertension and gene polymorphisms to assure safer cancer therapy.
We retrospectively studied 60 Japanese patients with metastatic colorectal cancer who had received bevacizumab-based chemotherapy. Genotypes were determined for five well-known functional single-nucleotide polymorphism of the VEGF gene at positions C-2578A, T-1498C, G-1154A, G-634C, and C936T. Hypertension was graded according to CTCAE v4.0 on the basis of home blood pressure.
The VEGF-2578 C/C and -1498 T/T genotypes were associated with significantly less hypertension during the first 2 months of bevacizumab-based chemotherapy (p = 0.004, p = 0.025, respectively). During the treatment period as a whole, the VEGF-2578 C/C and 936 C/C genotypes were associated with less hypertension (p = 0.031, p = 0.043, respectively). Preexisting hypertension was not associated with bevacizumab-related hypertension.
This study demonstrated a significant relation between a lower incidence of grade 2 or higher bevacizumab-related hypertension and the VEGF-2578 C/C genotype for the entire treatment period in Japanese patients with metastatic colorectal cancer. This genotype might be useful for ensuring safer treatment of patients who receive bevacizumab-based chemotherapy.
KeywordsBevacizumab Hypertension VEGF SNPs Colorectal cancer
- 5.Schneider BP, Wang M, Radovich M, Sledge GW, Badve S, Thor A et al (2008) Association of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 genetic polymorphisms with outcome in a trial of paclitaxel compared with paclitaxel plus bevacizumab in advanced breast cancer: ECOG 2100. J Clin Oncol 26:4672–4678PubMedCrossRefGoogle Scholar
- 7.Dahlberg SE, Sandler AB, Brahmer JR, Schiller JH, Johnson DH (2010) Clinical course of advanced non-small-cel lung cancer patients experiencing hypertension during treatment with bevacizumab in combination with carboplatin and paclitaxel on ECOG 4599. J Clin Oncol 28:949–954PubMedCrossRefGoogle Scholar
- 18.Koutras AK, Antonacopoulou AG, Eleftheraki AG, Dimitrakopoulos F-I, Koumarianou A, Varthalitis I et al (2011) Vascular endothelial growth factor polymorphisms and clinical outcome in colorectal cancer patients treated with irinotecan-base chemotherapy and bevacizumab. Pharmacogenomics J. doi:10.1038/tpj.2011.37