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Association of polymorphisms of angiogenesis genes with breast cancer

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

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 (HIF1α), 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.

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Acknowledgements

This work was supported by ASCO Career Development Award, Breast Cancer Research Foundation, Catherine Peachey Fund, GCRC CReFF Award & Indiana University Simon Cancer Center.

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Authors and Affiliations

  1. Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA

    Bryan P. Schneider, Milan Radovich, George W. Sledge, Jason D. Robarge, Lang Li, Anna M. Storniolo, Suzanne Lemler, Anne T. Nguyen, Bradley A. Hancock, Michael Stout, Todd Skaar & David A. Flockhart

  2. Indiana Cancer Pavilion, 535 Barnhill Drive, Rm 473, Indianapolis, IN, 46202, USA

    Bryan P. Schneider

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  1. Bryan P. Schneider
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  2. Milan Radovich
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  3. George W. Sledge
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Correspondence to Bryan P. Schneider.

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On Behalf of the “Friends for Life” Consortium.

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10549_2007_9755_MOESM1_ESM.doc

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Schneider, B.P., Radovich, M., Sledge, G.W. et al. Association of polymorphisms of angiogenesis genes with breast cancer. Breast Cancer Res Treat 111, 157–163 (2008). https://doi.org/10.1007/s10549-007-9755-9

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