Prognostic impact of VEGFA germline polymorphisms in patients with HER2-positive primary breast cancer

Anticancer Res. 2012 Sep;32(9):3619-27.

Abstract

Background: Vascular endothelial growth factor A (VEGFA) is essential in tumour angiogenesis, and polymorphisms in the VEGFA gene have been associated with breast cancer prognosis. The human epidermal growth factor receptor 2 (HER2) is overexpressed in breast tumours and is also associated with angiogenesis. We investigated the possible prognostic impact of VEGFA single nucleotide polymorphisms (SNPs) in patients with HER2-positive primary breast cancer.

Patients and methods: DNA was isolated from venous blood samples from 116 HER2-positive patients and genotyped for VEGFA -2578C>A, -1498T>C, -1154G>A, -634G>C, -7C>T and +936C>T SNPs using the TaqMan® SNP Genotyping Assay.

Results: The -2578C>A and -634G>C genotypes were associated with tumour size, p ≤ 0.014. In univariate analysis -2578CC, -634CC and -7CC genotypes were associated with inferior recurrence-free survival (p ≤ 0.028) but in cox multivariate analysis, only the -634CC genotype remained an independent prognostic factor (p=0.008).

Conclusion: The VEGFA -634CC genotype was found to be associated with an inferior prognosis for patients with HER2-positive breast cancer.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / genetics*
  • Chemotherapy, Adjuvant
  • Cyclophosphamide / administration & dosage
  • Docetaxel
  • Epirubicin / administration & dosage
  • Female
  • Fluorouracil / administration & dosage
  • Germ-Line Mutation
  • Humans
  • In Situ Hybridization, Fluorescence
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Prognosis
  • Receptor, ErbB-2 / biosynthesis*
  • Taxoids / administration & dosage
  • Vascular Endothelial Growth Factor A / genetics*

Substances

  • Taxoids
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Docetaxel
  • Epirubicin
  • Cyclophosphamide
  • Receptor, ErbB-2
  • Fluorouracil