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01.09.2008 | Epidemiology

Association of polymorphisms of angiogenesis genes with breast cancer

verfasst von: 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

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 1/2008

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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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Titel: Association of polymorphisms of angiogenesis genes with breast cancer
verfasst von: 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
Publikationsdatum: 01.09.2008
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 1/2008
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-007-9755-9

Springer Medizin

Association of polymorphisms of angiogenesis genes with breast cancer