RAD51 135G > C substitution increases breast cancer risk in an ethnic-specific manner: a meta-analysis on 21236 cases and 19407 controls
SCIENTIFIC REPORTS
Authors: Sekhar, Deepa; Pooja, Singh; Kumar, Sandeep; Rajender, Singh
Abstract
RAD51 is a homolog of bacterial RecA protein, which plays an important role in preserving stability of the genome. RAD51 interacts with BRCA1 and BRCA2 for homologous recombination repair. A functional polymorphism (135G > C) in the RAD51 gene has been a subject of great interest, which is evidenced by at least 28 case-control studies and eight meta-analyses undertaken on this polymorphism till now. We undertook a meta-analysis on RAD51 135G > C data for 21236 cases and 19407 controls pooled from 28 studies on breast cancer in women. Pooled data analysis suggested a significant association of the substitution with breast cancer in the recessive model (GG + GC versus CC) and in the co-dominant models comparing GG versus CC and GC versus CC. Analysis of the results suggested that 'CC' genotype is a significant breast cancer risk factor in comparison to 'GG' and 'GC' genotypes. We also undertook pooled analyses on different ethnic groups and found that 'CC' was a strong risk factor in Caucasians, but not in East-Asians and populations of mixed ethnicity. In conclusion, the RAD51 135G > C substitution in the homozygous form (CC) increases the risk of breast cancer in an ethnic-specific manner.
Polymorphism of XRCC3 in Egyptian Breast Cancer Patients
PHARMACOGENOMICS & PERSONALIZED MEDICINE
Authors: Alkasaby, Mona Khyri; Abd El-Fattah, Abeer Ibrahim; Ibrahim, Iman Hassan; Abd El-Samie, Hesham Samir
Abstract
Purpose: 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.