Association of polymorphisms of angiogenesis genes with breast cancer

Breast Cancer Res Treat. 2008 Sep;111(1):157-63. doi: 10.1007/s10549-007-9755-9. Epub 2007 Sep 20.

Abstract

Background: Few studies have systematically explored a pathway approach: to test the association of multiple polymorphisms from multiple genes important to angiogenesis simultaneously with risk of breast cancer. We report our preliminary data evaluating the association of polymorphisms from seven genes known to influence angiogenesis with the likelihood of having breast cancer.

Methods: We recruited 715 controls and 520 subjects with breast cancer. Subjects provided a blood specimen and completed a questionnaire that included common breast cancer risk factors and breast cancer status. We evaluated candidate polymorphisms in the following genes: Hypoxia Inducible Factor-1 alpha (HIF1alpha), Vascular Endothelial Growth Factor (VEGF), VEGF Receptor 1 (VEGFR-1), VEGFR-2, endothelial Nitric Oxide Synthase (eNOS), Neuropilin-1 (NRP-1) and Neuropilin-2 (NRP-2). Testing for associations between each polymorphism and the presence or absence of breast cancer was performed.

Results: VEGF-2578 AA and -1498 CC genotypes were more common in cancer cases than controls (P = 0.06 and P = 0.04, respectively). These two genotypes remained significant predictors of breast cancer status after adjusting for non-genetic risk factors estimated by the Gail model (P = 0.03 and P = 0.03, respectively). When comparing women with invasive versus pre-invasive breast cancer, the eNOS-786 TT and eNOS 894 GG genotypes were associated with a greater likelihood of invasive disease and the eNOS 894 GG genotype was associated with a greater likelihood of having metastatic disease.

Conclusion: There is an association of the VEGF-2578A and -1498C alleles with increased breast cancer risk. This association remains significant when adjusted for Gail score-related risk factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • African Americans
  • Breast Neoplasms / blood supply
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology*
  • Case-Control Studies
  • European Continental Ancestry Group
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Middle Aged
  • Neovascularization, Pathologic / genetics*
  • Neuropilin-1 / genetics
  • Neuropilin-2 / genetics
  • Nitric Oxide Synthase Type III / genetics
  • Polymorphism, Single Nucleotide*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Risk Factors
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor Receptor-1 / genetics
  • Vascular Endothelial Growth Factor Receptor-2 / genetics

Substances

  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Neuropilin-2
  • Vascular Endothelial Growth Factor A
  • Neuropilin-1
  • Nitric Oxide Synthase Type III
  • Vascular Endothelial Growth Factor Receptor-1
  • Vascular Endothelial Growth Factor Receptor-2