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Objective. The aim of this study was to investigate the role of APE1 Asp148Glu polymorphism in breast cancer progression in Saudi population. Methods. We examined the genetic variations (rs1130409) in the DNA base excision repair gene APE1 at codon 148 (Asp148Glu) and its association with breast cancer risk using genotypic assays and in silico structural as well as functional predictions. In silico structural analysis was performed with Asp148Glu allele and compared with the predicted native protein structure. The wild and mutant 3D structures of APE1 were compared and analyzed using solvent accessibility models for protein stability confirmation. Results. Genotypic analysis of APE1 (rs1130409) showed statistically significant association of Asp148Glu with elevated susceptibility to breast cancer. The in silico analysis results indicated that the nsSNP Asp148Glu may cause changes in the protein structure and is associated with breast cancer risk. Conclusion. Taken together, this is the first report that established that Asp148Glu variant has structural and functional effect on the APE1 and may play an important role in breast cancer progression in Saudi population.

Association of DNA Repair Gene APE1 Asp148Glu Polymorphism with Breast Cancer Risk