PMC:3319640 / 1981-4476 JSONTXT

{"project":"2_test","denotations":[{"id":"22496856-21351269-95990813","span":{"begin":195,"end":196},"obj":"21351269"},{"id":"22496856-17640039-95990814","span":{"begin":277,"end":278},"obj":"17640039"},{"id":"22496856-19561607-95990815","span":{"begin":403,"end":404},"obj":"19561607"},{"id":"22496856-19561604-95990816","span":{"begin":408,"end":409},"obj":"19561604"},{"id":"22496856-19786869-95990817","span":{"begin":413,"end":414},"obj":"19786869"},{"id":"22496856-19458483-95990818","span":{"begin":675,"end":676},"obj":"19458483"},{"id":"22496856-14740638-95990819","span":{"begin":680,"end":681},"obj":"14740638"},{"id":"22496856-21239167-95990820","span":{"begin":685,"end":686},"obj":"21239167"},{"id":"22496856-21402474-95990821","span":{"begin":690,"end":691},"obj":"21402474"},{"id":"22496856-17181841-95990822","span":{"begin":947,"end":949},"obj":"17181841"},{"id":"22496856-17181841-95990823","span":{"begin":1104,"end":1106},"obj":"17181841"},{"id":"22496856-11001067-95990824","span":{"begin":1233,"end":1235},"obj":"11001067"},{"id":"22496856-18452647-95990825","span":{"begin":1478,"end":1480},"obj":"18452647"},{"id":"22496856-18452647-95990826","span":{"begin":1662,"end":1664},"obj":"18452647"},{"id":"22496856-18650835-95990827","span":{"begin":1668,"end":1670},"obj":"18650835"},{"id":"22496856-18758482-95990828","span":{"begin":1754,"end":1756},"obj":"18758482"},{"id":"22496856-11566266-95990829","span":{"begin":1760,"end":1762},"obj":"11566266"},{"id":"22496856-17984175-95990830","span":{"begin":1847,"end":1849},"obj":"17984175"},{"id":"22496856-17369132-95990831","span":{"begin":1853,"end":1855},"obj":"17369132"},{"id":"22496856-15541813-95990832","span":{"begin":1947,"end":1949},"obj":"15541813"},{"id":"22496856-12505748-95990833","span":{"begin":1953,"end":1955},"obj":"12505748"},{"id":"22496856-11146397-95990834","span":{"begin":1959,"end":1961},"obj":"11146397"},{"id":"22496856-19009560-95990835","span":{"begin":2043,"end":2045},"obj":"19009560"},{"id":"22496856-17938959-95990836","span":{"begin":2049,"end":2051},"obj":"17938959"},{"id":"22496856-19904558-95990837","span":{"begin":2055,"end":2057},"obj":"19904558"}],"text":"Introduction\nWorldwide, colorectal cancer (CRC) is the third most common malignancy and the fourth leading cause of cancer death with an estimated 1,234,000 new cases and 608,000 deaths in 2008 [1]. CRC is a disease that is largely influenced by lifestyle and dietary factors [2], however, recent studies have suggested that inter-individual genetic variations may significantly affect the risk of CRC [3], [4], [5]. In addition, accumulating evidence, including those from our own studies, has also shown that single nucleotide polymorphisms (SNPs) may be used as surrogate biomarkers of the genetic background of CRC patients to predict therapeutic response and prognosis [6], [7], [8], [9].\nTumor angiogenesis, the generation of new blood vessels, is a crucial cellular process that influences tumor cell growth, invasion, local-regional recurrence, and metastatic spread of CRC, making it an attractive target for anticancer drug development [10].The tumor cell growth, invasion, and metastases are heavily influenced by the balance of functions of endogenous angiogenic and anti-angiogenic factors [10]. The vascular endothelial growth factors (VEGFs) and its receptors (VEGFRs) play a central role in the angiogenesis pathway [11]. The functional inhibitors of VEGF and VEGFRs, such as anti-VEGF neutralizing antibody and small molecules that block the tyrosine kinase activity of VEGFRs, have been approved as anti-angiogenesis therapies for many cancers, including CRC [12]. However, the wide resistance to the anti-angiogenic therapies targeting the VEGF pathway stimulated the search for treatments targeting the VEGF-independent angiogenesis pathway [12], [13], such as pro-angiogenic pathways mediated by angiopoietins/TIE-2 and Delta/Notch [14], [15], as well as anti-angiogenic pathways mediated by angiomotin and endoglin proteins [16], [17].\nGenetic variations in the VEGF gene have been reported to modulate VEGF gene expression [18], [19], [20]. They have also been associated with the etiology and clinical outcomes of CRC [21], [22], [23]. However, although basic studies have revealed an essential role of VEGF-independent pathway genes in the etiology and clinical outcome of CRC, no study has been reported on the association between the genetic variations of these genes and CRC prognosis. The aim of the current pilot study was to evaluate the association between SNPs in several major VEGF-independent angiogenic pathway genes with the overall survival of CRC patients."}