Cancer Chemotherapy and Pharmacology

, Volume 71, Issue 2, pp 405–411 | Cite as

Association between bevacizumab-related hypertension and vascular endothelial growth factor (VEGF) gene polymorphisms in Japanese patients with metastatic colorectal cancer

  • Sachi Morita
  • Keisuke Uehara
  • Goro Nakayama
  • Takashi Shibata
  • Tomoyo Oguri
  • Megumi Inada-Inoue
  • Tomoya Shimokata
  • Mihoko Sugishita
  • Ayako Mitsuma
  • Yuichi Ando
Original Article



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.


Bevacizumab Hypertension VEGF SNPs Colorectal cancer 


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Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Sachi Morita
    • 1
  • Keisuke Uehara
    • 2
  • Goro Nakayama
    • 3
  • Takashi Shibata
    • 1
  • Tomoyo Oguri
    • 4
  • Megumi Inada-Inoue
    • 1
  • Tomoya Shimokata
    • 1
  • Mihoko Sugishita
    • 1
  • Ayako Mitsuma
    • 1
  • Yuichi Ando
    • 1
  1. 1.Department of Clinical Oncology and ChemotherapyNagoya University HospitalShowa-ku, NagoyaJapan
  2. 2.Division of Surgical Oncology, Department of SurgeryNagoya Graduate School of MedicineShowa-ku, NagoyaJapan
  3. 3.Department of Gastroenterological SurgeryNagoya Graduate School of MedicineShowa-ku, NagoyaJapan
  4. 4.Department of Respiratory MedicineNagoya Graduate School of MedicineShowa-ku, NagoyaJapan

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