Association of VEGF and KDR single nucleotide polymorphisms with colorectal cancer susceptibility in Koreans

Abstract

Vascular endothelial growth factor (VEGF) and its receptor kinase insert domain-containing receptor (KDR) play crucial roles in angiogenesis, which contributes to the development and progression of solid tumors. The aim of this study was to investigate the associations of VEGF (-2578C > A, -1154G > A, -634G > C, and 936C > T) and KDR (-604T > C and 1192G > A) polymorphisms with the development of colorectal cancer (CRC). A total of 882 participants (390 CRC patients and 492 controls) were enrolled in the study. The genotyping of VEGF and KDR polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism assay. We found that the CT and TT genotype of the 936C > T was associated with an increased risk of CRC compared with the CC genotype as the dominant model for the T allele. In addition, we also found a increased CRC risk with TC + CC genotype of KDR -604T > C compared with TT genotype in CRC patients and control subjects. Similarly, KDR 1192G > A also showed significant association between 1192G > A variants and risk of CRC. In the haplotype analyses, haplotype -2578A/-1154A/-634G/936T of VEGF polymorphisms and haplotype -604C/1192G and -604C/1192A of KDR polymorphisms were associated with an increased susceptibility of CRC. Our results suggest that the VEGF 936C > T, KDR -604T > C, and KDR 1192G > A polymorphisms may be contribute to CRC risk in the Korean population.

VEGF Gene Polymorphisms and Susceptibility to Colorectal Cancer

“…However, the + 936T allele increases the risk for CRC in Korean and Chinese populations (Bae et al, 2008;Wu et al, 2009). Similarly, Jang et al (2013aJang et al ( , 2013b found that VEGF GENE POLYMORPHISMS AND COLORECTAL CANCER the + 936T allele was associated with an increased susceptibility to CRC. In gastric cancer, Tzanakis et al (2006) found a strong association between the -2578AA, + 936CT, and + 936TT genotypes and a larger tumor size, and the -2578AA genotype was strongly correlated to poor differentiation.…”

“…Although it has been indicated that VEGF could be a good marker for determining the risk of developing CRC and could be used as a therapeutic target for new molecular anticancer drugs (Hanrahan et al, 2003;Fernando and Hurwitz, 2004;Dassoulas et al, 2009;Vidaurreta et al, 2010), the data remain conflicting if VEGF gene polymorphisms are associated with the prognosis of CRC (Yamamori et al, 2004;Park et al, 2007;Bae et al, 2008;Maltese et al, 2009;Wu et al, 2009;Hansen et al, 2010b;Antonacopoulou et al, 2012;Jang et al, 2013b). Therefore, to test this hypothesis, we investigated possible associations between genetic variations at the -2578A > C, + 936C > T, and -460C > T polymorphic site in the VEGF gene, in patients who have had CRC compared to healthy individuals.…”

Genetic Variations of Kinase Inserts Domain Receptor (KDR) Gene Are Associated with the Risk of Astrocytomas

“…At the same time, KDR polymorphisms were widely studied in recent years. For example, Jang et al found KDR SNPs (1192G>A) could reduce the risk of colorectal cancer in Koreans [33]. KDR variation (rs2305945, G/T) can lead to ovarian hyperstimulation syndrome in Travis's research [34].…”

Interplay between 3′-UTR polymorphisms in the vascular endothelial growth factor (VEGF) gene and metabolic syndrome in determining the risk of colorectal cancer in Koreans

“…The VEGF 1612A allele was associated with increased gastric cancer risk [ 23 ]. The 936C > T polymorphism and its link to CRC susceptibility have been published by our laboratory and others [ 6 , 24 ]. The other three single nucleotide polymorphisms (SNPs) in the VEGF 3′-UTR, 1451C > T, 1612G > A, and 1725G > A, are poorly understood in the context of their genetic contributions to CRC susceptibility.…”