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

Research output: Contribution to journalArticle

8 Scopus citations


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 angiogen-esis 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 (HIF1a), vascular endothelial growth factor (VEGF), VEGF-recep-tor 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 HIF1a 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.

Original languageEnglish (US)
Pages (from-to)543-549
Number of pages7
JournalBreast Cancer Research and Treatment
Issue number3
StatePublished - Aug 1 2009



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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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