Medizinische Universität Graz - Research portal
Selected Publication:
Seitinger, M.
A common 936 C/T polymorphism in the gene of vascular endothelial growth factor and its association with breast cancer risk
[ Dissertation ] Medical University of Graz; 2003. pp.
- Authors Med Uni Graz:
- Advisor:
- Renner Wilfried
- Samonigg Hellmut
- Altmetrics:
- Abstract:
- Breast cancer is he 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. The most important regulator of angiogenesis is vascular endothelial growth factor (VEGF), a dimeric glycoprotein which is overexpressed in several tumor tissues. VEGF plasma levels are highly predictive for tumor growth and survival rate of patients. Thus, therapeutic strategies blocking VEGF action can inhibitor tumor growth. In a study including 23 healthy young men, a common 936 C/T polymorphism in the 3 untranslated region of the VEGF gene has been associated with VEGF plasma levels, showing strongly reduced levels in carriers of a 936-T allele. This has lead to the hypothesis that this genetic marker may be similarly associated with VEGF plasma levels in women and might influence the risk for breast cancer. The present large case-control study was designed to investigate these hypotheses. VEGF genotype was determined in 500 women with breast cancer and 500 sex- and age-matched healthy control subjects. Carriers of a 936T-allele were more frequent among controls (29,4%) than among patients (17,6%, p=0,000014), indicating that this genetic variant may be protective against breast cancer. The odds ratio for carriers of a 936T-allele for breast cancer was 0,51 (95% confidence interval 0,38-0,70).