Population-Based Case-Control Study of VEGF Gene Polymorphisms and Breast Cancer Risk among Chinese Women

Abstract

Vascular endothelial growth factor (VEGF) is a major angiogenic factor involved in a number of pathologic processes, including neovascularization, a crucial step in the development of solid malignancies. Using data and specimens collected in the Shanghai Breast Cancer Study, a population-based case-control study conducted in urban Shanghai, China from 1996 to 1998, we evaluated the association of VEGF gene polymorphisms with breast cancer risk. Included in this study were 1,093 cases and 1,184 agematched controls who had completed an in-person interview and donated a blood sample to the study. Polymorphisms in the promoter region (TÀ460C), 5 ¶ untranslated region (C+405G), and 3 ¶untranslated region (C936T) were genotyped using the Taqman allelic discrimination assay. No statistically significant case-control difference was found for the C+405G and TÀ460C polymorphisms. However, the C936T polymorphism was associated with a reduced risk of breast cancer. Compared with CC genotype carriers, women who had the TT genotype showed a decreased risk [odds ratio (OR), 0.65; 95% confidence interval (95% CI) 0.41-1.02], and the inverse association was restricted to premenopausal women (OR, 0.45; 95% CI, 0.25-0.79). Six common haplotypes were identified. Compared with the most common haplotype (À460T/405C/936C), the À460T/405G/936T haplotype was associated with a reduced risk of breast cancer (OR, 0.67; 95% CI, 0.43-1.04), particularly in premenopausal women (OR, 0.47; 95% CI, 0.27-0.81). Our study suggests that the VEGF C936T polymorphism might be a susceptibility factor for breast cancer among Chinese women. (Cancer Epidemiol Biomarkers Prev 2006;15(6):1148 -52 )

Vascular endothelial growth factor +936C/T polymorphism and cancer risk in Asians: a meta-analysis

“…Taking breast cancer as an example, similar frequencies of VEGF +936C/T genotypes between cases and controls were reported by Jacobs et al (2006). In contrast, Krippl et al (2003), Kataoka et al (2006), andJakubowska et al (2008) suggested that VEGF +936T is a protective factor against breast cancer. However, Balasubramanian et al (2007) found that VEGF +936C was associated with decreased breast cancer risk when combined with -460T and +405C.…”

“…The exact mechanism for how VEGF +936C/T acted on the carcinogenic procedure was not clear. In recent years, intense genetic research efforts have been made in this field, and the results produced have been conflicting (Krippl et al, 2003;Jacobs et al, 2006;Kataoka et al, 2006;Balasubramanian et al, 2007;Jakubowska et al, 2008). The leading potential explanation for the association was that the DNA sequence variation may alter VEGF production and/or activity (Renner et al, 2000), thereby causing differences in the development of tumors (Kim et al, 2010).…”

“…In total, 21 studies (Abe et al, 2002;Kataoka et al, 2006;Hsiao et al, 2007;Amano et al, 2008;Bae et al, 2008a,b;Chae et al, 2006Chae et al, , 2008Cheng et al, 2008;Ke et al, 2008;Hsing et al, 2008;Al-Moundhri et al, 2009;Tahara et al, 2009;Wu et al, 2009;Li et al, 2010;Kim et al, 2010;Bao et al, 2011;Beeghly-Fadiel et al, 2011;Kang et al, 2011;Zhou et al, 2011) comprising 8298 cancer cases and 8053 controls were included in the meta-analysis. The VEGF allele +936T frequency was 17.78% in cases and 17.84% in controls.…”

Vascular Endothelial Growth Factor (VEGF) Gene Polymorphisms and Breast Cancer Risk in a Chinese Population

“…The results found that the 936CT+TT genotypes of VEGF reduced BRCA1-associated breast cancer risk in Polish women (Jakubowska et al, 2008). A population-based case-control study conducted in urban Shanghai, China from 1996 to 1998, suggested that the VEGF C936T polymorphism might be a susceptibility factor for breast cancer among Chinese women (Kataoka et al, 2006). A large case-control study found that the VEGF -634CC genotype and the VEGF -2578/-634 CC haplotype were significantly associated with high tumor aggressiveness (large tumor size and high histologic grade) and the VEGF -2578AA genotype and the VEGF -2578/-634 AG haplotype with low histologic grade tumors (Jin et al, 2005).…”

“…The associations between three VEGF gene polymorphisms (-634 G/C, +936 C/T, and +1612 G/A) and breast cancer risk have been extensively studied, and the currently available results are inconclusive (Krippl et al, 2003;Jin et al, 2005;Lu et al, 2005;Jacobs et al, 2006;Kataoka et al, 2006;Eroglu et al, 2008;Jakubowska et al, 2008;Langsenlehner et al, 2008;Schneider et al, 2008;Wehrschuetz et al, 2009;Gu and Wang, 2011;Jin et al, 2011;Liu et al, 2011;Oliveira et al, 2011;Qiu et al, 2011;Wang et al, 2011;Yang et al, 2011;Rodrigues et al, 2012). The aim of this study was to investigate the association between three VEGF gene polymorphisms and breast cancer risk in Chinese Han patients.…”