Epidemiology

Breast Cancer Research and Treatment

, Volume 116, Issue 3, pp 543-549

First online:

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

  • Bryan P. SchneiderAffiliated withDepartment of Medicine, Indiana University School of MedicineIndiana Cancer Pavilion Email author 
  • , Milan RadovichAffiliated withDepartment of Medicine, Indiana University School of Medicine
  • , David A. FlockhartAffiliated withDepartment of Medicine, Indiana University School of Medicine
  • , Janet S. CarpenterAffiliated withDepartment of Adult Health, Indiana University School of Nursing
  • , Lang LiAffiliated withDepartment of Medicine, Indiana University School of Medicine
  • , Jason D. RobargeAffiliated withDepartment of Medicine, Indiana University School of Medicine
  • , Anna M. StornioloAffiliated withDepartment of Medicine, Indiana University School of Medicine
  • , Bradley A. HancockAffiliated withDepartment of Medicine, Indiana University School of Medicine
  • , Todd C. SkaarAffiliated withDepartment of Medicine, Indiana University School of Medicine
    • , George W. SledgeAffiliated withDepartment of Medicine, Indiana University School of Medicine

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Abstract

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.

Keywords

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