AXIN2 polymorphisms, the β-catenin destruction complex expression profile and breast cancer susceptibility

Background: The Wnt/β-catenin signaling pathway is an important regulator of cellular functions such as proliferation, survival and cell adhesion. Wnt/β-catenin signaling is associated with tumor initiation and progression; β-catenin mutations explain only 30% of aberrant signaling found in breast cancer, indicating that other components and/or regulation of the Wnt/β-catenin pathway may be involved. Objective: We evaluated AXIN2 rs2240308 and rs151279728 polymorphisms, and expression profiles of β-catenin destruction complex genes in breast cancer patients. Materials and Methods: We collected peripheral blood samples from 102 breast cancer and 102 healthy subjects. The identification of the genetic variation was performed using PCR-RFLPs and DNA sequencing. RT-qPCR was used to determine expression profiles. Results: We found significant association of AXIN2 rs151279728 and rs2240308 polymorphisms with breast cancer risk. Significant increase was observed in AXIN2 level expression in breast cancer patients. Further analyses showed APC, β-catenin, CK1α, GSK3β and PP2A gene expression to be associated to clinic-pathological characteristics. Conclusions: The present study demonstrated, for the first time, that AXIN2 genetic defects and disturbance of β-catenin destruction complex expression may be found in breast cancer patients, providing additional support for roles of Wnt/β-catenin pathway dysfunction in breast cancer tumorigenesis. However, the functional consequences of the genetic alterations remain to be determined.