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SHR Neuro Cancer Cardio Metab Microb Lipid

VEGF-polymorphisms and breast cancer risk

Abstract
Angiogenesis plays an important role for breast cancer development and growth
Breast cancer is the most frequently diagnosed cancer in Western Societies, with a lifetime incidence of about 10 - 13% among women . The etiology of breast cancer is still not fully understood. Besides age at menarche and menopause, diet, reproductive history, estrogen administration and genetic factors have been suggested as risk factors . Only a small part of familial breast cancer cases can be explained by inherited mutations, the majority being most probably explained by a combination of common low-penetrance gene polymorphisms.
Tumor growth requires the formation of new blood vessels, a process called angiogenesis. Angiogenesis is a complex multifactorial process involving a variety of angiogenic and proteolytic enzyme activators and inhibitors. The majority of the genes encoding these factors carry single nucleotide polymorphisms (SNPs), with some of them leading to altered activity.
Vascular endothelial growth factor (VEGF) is a key player in angiogenesis
The most important regulator of angiogenesis is vascular endothelial growth factor (VEGF), a dimeric glycoprotein which is overexpressed in several tumor tissues. VEGF is a disulfide-bonded dimeric glycoprotein, sharing close sequence homology with placenta growth factor, VEGF-B and VEGF-C, and lower sequence homology with platelet-derived growth factor (PDGF).VEGF plasma levels are highly predictive for tumor growth and survival rate of patients and therapeutic strategies blocking VEGF action sucessfully inhibited tumor growth.
Genetic variants of VEGF may influence breast cancer risk
Several SNPs have been described in the VEGF gene, some of them have been associated with VEGF expression and/or clinical phenotypes (table 1). We have previously analyzed he role of one variants, 936C>T, as potential risk factor for breast cancer. In that study carriers of a T936 allele had an approximately 50% decreased risk for breast cancer. Currently no data are available about the role for other VEGF polymorphisms for breast cancer.
Keywords
human genetics
pharmacodynamics
pharmacokinetics
internal medicine
Angiogenese
Brustkrebs
Genetik
Risikofaktor
Project Leader:
Langsenlehner Uwe
Duration:
01.01.2004-31.07.2005
Programme:
Jubiläumsfonds (ÖNB)
Type of Research
basic research
Staff
Langsenlehner U., Project Leader
Krippl P., Co-worker
Weitzer W., Co-worker
Langsenlehner T., Co-worker
Renner W., Co-worker
Hofmann G., Co-worker
MUG Research Units
Clinical Institute of Medical and Chemical Laboratory Diagnostics
Department of Radiology
Department of Therapeutic Radiology and Oncology
Division of Oncology
Project partners
Medizinische Universität Innsbruck, Austria
Funded by
Österreichische Nationalbank (Jubiläumsfonds), Otto Wagner Platz 3, A-1090 Wien, Austria
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