The association of VEGF rs833061 and rs2010963 polymorphisms with susceptibility to colorectal cancer in an Iranian population

1

Introduction

It is estimated that more than seven million people died of cancer around the world. Many biomarkers and Signaling pathways are involved in the cancer development process that awareness of these factors is essential for the prognosis, diagnosis and treatment of cancer 123 . Colorectal cancer (CRC) is a common life-threatening malignancy in the world [4] . Approximately 1million people are being diagnosed with CRC every year and its prevalence, as a multifactorial disease, is increasing all over the world [5] . CRC arises through a multistep carcinogenic process in which genetic changes occur due to mutations of several genes [6] . The angiogenesis factors improve the growth, development, and progression of solid tumors by forming new blood vessels from endothelial precursors [7] .

The vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen involved in several pathologic processes, including angiogenesis, tumor development and metastasis [8] . Evidence showed that an increase in VEGF expression and microvessel’s density in solid tumors is associated with the advanced stages of the tumor, which leads to poor prognosis for various types of cancers, including CRC [910] . VEGF protein is encoded by the VEGF gene located at chromosome 6p21.3 [11] . Anyway, no studies have been conducted that have investigated the single nucleotide polymorphisms (SNPs) of the VEGF gene and their relationship to the susceptibility of CRC. Accordingly, the present study investigated the relation of two VEGF gene polymorphisms (405C > G and − 460C > T) with the CRC susceptibility and clinicopathological characteristics in the Iranian population [1213] .

Genome-wide association studies (GWAS) have identified several single-nucleotide polymorphisms (SNPs) in candidate genes involved in CRC [13] . The VEGF gene is highly polymorphic and the two important 405C > G (rs2010963) and − 460C > T (rs833061) polymorphisms in this gene are reported to influence the expression of the VEGF gene [1415] . One of these SNPs is located on the promoter region and another in the 5՜ untranslated region (UTR) of the VEGF gene and has been suggested as the candidate markers in several malignant diseases including CRC [1617] . So far, 20 different studies have evaluated the association of rs2010963and rs833061with the risk of colon cancer incidence. Almost half of them have reported significant results ( Table 1 ).