Pharmacogenomics and Personalized Medicine (Aug 2020)
Polymorphism of XRCC3 in Egyptian Breast Cancer Patients
Abstract
Mona Khyri Alkasaby,1 Abeer Ibrahim Abd El-Fattah,1 Iman Hassan Ibrahim,1 Hesham Samir Abd El-Samie2 1Department of Biochemistry and Molecular Biology, Faculty of Pharmacy (Girls), Al-Azhar University, Nasr City, Cairo, Egypt; 2Department of Clinical Pathology, Faculty of Medicine (New Damietta), Al-Azhar University, New Damietta, Damietta, EgyptCorrespondence: Iman Hassan IbrahimDepartment of Biochemistry and Molecular Biology, Faculty of Pharmacy (Girls), Al-Azhar University, Nasr City 11759, Cairo, EgyptTel +20 1001729242Email [email protected]: Polymorphisms of DNA repair genes may contribute to variations in DNA repair capacity and subsequent genetic susceptibility to different cancers. In Egypt, breast cancer is the most common cancer among women, representing 18.9% of the total cancer cases. The present study assesses the correlation between X-ray repair cross-complementing group 3 (XRCC3) polymorphism with breast cancer and treatment response in Egyptian female breast cancer patients.Patients and Methods: This pilot case–control study was conducted on 66 female breast cancer patients and 20 apparently healthy females as a control group. Tumor grading, immunohistostaining of hormone (progesterone and estrogen) receptors and human epidermal growth factor receptor 2 (HER2), and RFLP-PCR for XRCC3 (rs861539) polymorphism were performed. All breast cancer patients received a treatment protocol (after surgery) which was either chemotherapy (anthracyclines followed by paclitaxel or anthracyclines + fluorouracil) or radiotherapy, or both. Disease-free survival (DFS) and overall survival (OS) were recorded.Results: The number of patients with a heterozygous allele (GA) was significantly higher in cases of tumor size > 20 mm. The A allele was correlated with younger age at diagnosis in both chemotherapy and radiotherapy groups. Poor treatment response and higher mortality rates were significantly associated with AA and GA compared with GG alleles (normal allele). In the chemotherapy group, out of eight patients with the A allele, six showed a poor response to treatment containing fluorouracil.Conclusion: XRCC3 rs861539 polymorphism could be associated with lower DFS and OS and poor treatment response. So, we recommend carrying out XRCC3 genotyping before starting treatment to choose the most effective treatment strategy according to XRCC3 polymorphism.Keywords: breast cancer, gene polymorphism, XRCC3, treatment response, survival
