Different effection of p.1125Val>Ala and rs11954856 in APC on Wnt signaling pathway

Oncotarget. 2017 Aug 5;8(41):70854-70864. doi: 10.18632/oncotarget.20106. eCollection 2017 Sep 19.

Abstract

Colorectal cancer (CRC) is among the most common and fatal forms of solid tumors worldwide and more than two thirds of CRC and adenomas patients have APC gene mutations. APC is a key regulator in the Wnt/β-catenin signaling pathway but its roles in CRC remains to be elucidated. In this study, we compared APC genes between CRC patients and controls to determine possible associations of nucleotide changes in the APC gene with the pathways involved in CRC pathogenesis. All participants received physical and enteroscopic examinations. The APC gene was sequenced for 300 Chinese Han CRC patients and 411 normal controls, and the expression levels of genes in the signaling pathway were analyzed using Western Blotting. Statistical analyses were conducted using SPSS (version 19.0) software. We found that rs11954856 in the APC gene was associated with colorectal cancer and could increase the expression levels of APC, β-catenin, TCF7L1, TCF7L2 and LEF1 genes in the pathway in the CRC patients, demonstrating the involvement of APC in the pathological processes leading to CRC.

Keywords: APC; Wnt/β-catenin signaling pathway; colorectal cancer; gene expression; mutation.