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

• Published in: Breast cancer research and treatment Vol. 116; no. 3; pp. 543 - 549
• Main Authors: Schneider, Bryan P., Radovich, Milan, Flockhart, David A., Carpenter, Janet S., Li, Lang, Robarge, Jason D., Storniolo, Anna M., Hancock, Bradley A., Skaar, Todd C., Sledge, George W.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.08.2009; Springer; Springer Nature B.V
• Subjects: Angiogenesis; Angiogenic Proteins - genetics; Biological and medical sciences; Breast - metabolism; Breast - pathology; Breast cancer; Breast Neoplasms - blood supply; Breast Neoplasms - epidemiology; Breast Neoplasms - genetics; Cancer research; Cancer therapies; Carcinoma, Intraductal, Noninfiltrating - blood supply; Carcinoma, Intraductal, Noninfiltrating - epidemiology; Carcinoma, Intraductal, Noninfiltrating - genetics; Cross-Sectional Studies; Dermatology; Epidemiology; Female; Genes; Genotype; Gynecology. Andrology. Obstetrics; Hot Flashes - genetics; Hot Flashes - pathology; Humans; Hypoxia-Inducible Factor 1, alpha Subunit - genetics; Mammary gland diseases; Medical sciences; Medicine; Medicine & Public Health; Menopause; Neoplasm Invasiveness; Neovascularization, Pathologic - genetics; Neuropilin-1 - genetics; Neuropilin-2 - genetics; Nitric Oxide Synthase Type III - genetics; Oncology; Polymorphism; Polymorphism, Genetic - genetics; Risk Factors; Skin involvement in other diseases. Miscellaneous. General aspects; Statistics as Topic; Tumors; Vascular disorders of the skin; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor Receptor-2 - genetics; Angiogenesis; Hot flash; Endothelial nitric oxide synthase; Breast cancer; Single nucleotide polymorphism; Hypoxia inducible factor 1-alpha; Skin disease; Breast disease; Genetic variability; Enzyme; Cardiovascular disease; Genotype; Malignant tumor; Hot flush; Nitric-oxide synthase; Vascular disease; Mammary gland diseases; Hypoxia inducible factor I-alpha; Gene; Genetics; Transcription factor HIF1; Oxidoreductases; Neovascularization; Erythema; Cancer
• ISSN: 0167-6806; 1573-7217; 1573-7217
• DOI: 10.1007/s10549-008-0178-z

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.