Genetic Variation in VEGF Family Genes and Breast Cancer Risk: A Report from the Shanghai Breast Cancer Genetics Study

Abstract

Background In addition to mediating aspects of physiological and pathological angiogenesis, the vascular endothelial growth factor (VEGF) family also contributes to carcinogenesis. Methods We comprehensively characterized genetic variation across four VEGF family genes and evaluated associations with breast cancer risk with odds ratios and 95% confidence intervals (OR, 95% CI) for participants of the two-stage case-control Shanghai Breast Cancer Genetics Study (SBCGS). Stage 1 evaluated 200 single nucleotide polymorphisms (SNPs) across two VEGF ligands (VEGFA and VEGFC) and two VEGF receptors (FLT1/VEGFR1 and KDR/VEGFR2) among 2,079 cases and 2,148 controls. Five SNPs with promising associations were assessed in Stage 2 among 4,419 cases and 1,851 controls. Results Two SNPs were consistently associated with breast cancer risk across our two study stages, and significant in combined analyses. Compared to FLT1 rs9551471 major allele homozygotes (AA), reduced risks were associated with AG (OR=0.92, 95% CI: 0.84-1.00) and GG (OR=0.78, 95% CI: 0.64-0.95) genotypes (p-value for trend = 0.005). Compared to VEGFA rs833070 major allele carriers (CC or CT), increased risk was associated with TT genotypes (OR=1.26, 95% CI: 1.05-1.52, p-value = 0.016). Conclusion Results from our study indicate that common genetic variation in VEGFA and FLT1 (VEGFR1) may contribute to breast cancer susceptibility. Impact Our findings provide clues for future studies on VEGF family genes in relation to cancer susceptibility and survival.

Genetic Variants of VEGF (rs201963 and rs3025039) and KDR (rs7667298, rs2305948, and rs1870377) Are Associated with Glioma Risk in a Han Chinese Population: a Case-Control Study

“…Elevated levels of VEGF are commonly seen in a variety of solid tumors and associated with an advanced stage and poor prognosis of cancer [28][29][30][31]. A number of studies have investigated the role of VEGF SNPs in cancer susceptibility, including breast [19], lung [17], colorectal [32], and gastric cancers [21]. However, no conclusive evidence can be obtained from the inconsistent results in the published studies.…”

“…Genetic variants in KDR may be responsible for pathogenesis, such as chronic myeloid leukemia [37], breast cancer [19], and colorectal cancer [38]. Dong et al suggested that two SNPs (rs10013228 and rs2071559) in the KDR have a close association with a reduced risk of colorectal cancer recurrence [38].…”

“…Dong et al suggested that two SNPs (rs10013228 and rs2071559) in the KDR have a close association with a reduced risk of colorectal cancer recurrence [38]. No significant association between KDR polymorphisms and breast cancer susceptibility has been reported in the study of Beeghly-Fadiel et al [19]. Kim et al suggested that the genetic variations in KDR gene were revealed to be associated with cytogenetic response and treatment failure in chronic myeloid leukemia [37].…”

“…Two genetic variants, rs2010963 in the 5′ untranslated region and rs3025039 in the 3′ untranslated region, were reportedly correlated with an increased level of plasma VEGF [15,16]. Polymorphisms of VEGF have been revealed to be related to risks of lung, colorectal, breast, oral, ovarian, gastric, and bladder cancers [17][18][19][20][21][22]. Meanwhile, two SNPs in KDR are implicated in the susceptibility to coronary artery disease [23], stroke [24], and age-related macular degeneration [25].…”

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

“…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.…”