Breast Cancer Research and Treatment

, Volume 116, Issue 3, pp 543–549 | Cite as

Exploratory study evaluating the association of polymorphisms of angiogenesis genes with hot flashes

  • Bryan P. Schneider
  • Milan Radovich
  • David A. Flockhart
  • Janet S. Carpenter
  • Lang Li
  • Jason D. Robarge
  • Anna M. Storniolo
  • Bradley A. Hancock
  • Todd C. Skaar
  • George W. Sledge


Purpose Hot flashes are a common symptom and an important cause of decreased quality of life in women with breast cancer. Hot flashes involve vasodilatation and flushing, however, their complex etiology is not fully understood. We evaluated the association between germline polymorphisms in genes important to angiogenesis and subjective reporting of hot flashes. Experimental design We recruited 1,244 subjects; 520 were breast cancer cases, 715 were documented healthy controls, and nine were of unknown status. Subjects were asked to provide a blood specimen and complete a questionnaire which included whether they had recently or had ever experienced hot flashes. We evaluated candidate polymorphisms in the following genes: hypoxia inducible factor-1 alpha (HIF1α), vascular endothelial growth factor (VEGF), VEGF-receptor 2 (VEGFR-2), endothelial nitric oxide synthase (eNOS), neuropilin-1 (NRP-1), and NRP-2. Testing for an association between polymorphisms and a history of current flashes or ever having hot flashes was performed. Results 441 premenopausal and 533 postmenopausal, Caucasian women were evaluable for hot flash analysis. For premenopausal women the eNOS-786 CT and TT genotypes were significantly associated with a greater likelihood of a subject reporting current hot flashes than the CC genotype (P = 0.03). After adjusting for clinical variables, the genotype association was no longer significant (P = 0.08). For postmenopausal women, the HIF1α 1744 CT and TT genotypes were significantly associated with a greater likelihood of a subject reporting current hot flashes (P = 0.05) and this remained significant after consideration of established clinical variables (P = 0.04). Conclusion Hot flashes may be regulated by genes that control angiogenesis.


Hot flash Breast cancer Single nucleotide polymorphism Hypoxia inducible factor 1-alpha Endothelial nitric oxide synthase Angiogenesis 



Supported by: ASCO Career Development Award (BPS), Catherine Peachey Fund (BPS), Indiana University GCRC CReFF Award (BPS), Breast Cancer Research Foundation (GWS), K24 and 401 from NIH, Bethesda. MD (DAF) & Indiana University Melvin, Bren Simon Cancer Center and on behalf of the Friends for Life Consortium.


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Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Bryan P. Schneider
    • 1
    • 2
  • Milan Radovich
    • 1
  • David A. Flockhart
    • 1
  • Janet S. Carpenter
    • 3
  • Lang Li
    • 1
  • Jason D. Robarge
    • 1
  • Anna M. Storniolo
    • 1
  • Bradley A. Hancock
    • 1
  • Todd C. Skaar
    • 1
  • George W. Sledge
    • 1
  1. 1.Department of MedicineIndiana University School of MedicineIndianapolisUSA
  2. 2.Indiana Cancer PavilionIndianapolisUSA
  3. 3.Department of Adult HealthIndiana University School of NursingIndianapolisUSA

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