title: BRCA1 Gene Mutations and Influence of Chemotherapy on Autophagy and Apoptotic Mechanisms in Egyptian Breast Cancer Patients.
abstract: BACKGROUND
  It is well established that mutations in the BRCA1 gene are a major risk factor for breast cancer. Induction of cancer cell death and inhibition of survival are the main principles of cancer therapy. In this context, autophagy may have dual roles in cancer, acting on the one hand as a tumor suppressor and on the other as a mechanism of cell survival that can promote the growth of established tumors. Therefore, understanding the role of autophagy in cancer treatment is critical. Moreover, defects in apoptosis, programmed cell death, may lead to increased resistance to chemotherapy.
  
  
  OBJECTIVE
  The aim of the present study was to detect BRCA1 gene mutations in order to throw more light on their roles as risk factors for breast cancer in Egypt. Secondly the role of autophagy and apoptosis in determining response to a fluorouracil, doxorubicin, cyclophosphamide (FAC) regimen was investigated.
  
  
  METHODS
  Forty-five female breast cancer cases and thirty apparently healthy females were enrolled in the present study. Serum levels of autophagic biomarkers, Beclin 1 and LC3 as well as the serum levels of apoptosis biomarkers Bcl-2 and Caspase-3 were measured before and after chemotherapy.
  
  
  RESULTS
  BRCA1 mutations were found in 5 (16.7%) and 44 (99.8%) of the controls and cancer patients, the most frequent being 5382insC followed by C61G and 185 delAG. The results revealed that chemotherapy caused elevation in serum concentration levels of the autophagic biomarkers (Beclin 1 and LC3). This elevation was associated with a significant decrease in serum concentration levels of Bcl-2 and significant increase in caspase-3 concentration levels (apoptotic markers).
  
  
  CONCLUSIONS
  The results of the present study indicate a very high level of BRCA mutations in breast cancer cases in Egypt and point to involvement of autophagic and apoptotic machinery activation in response to FAC chemotherapy.
authors.affiliation: Applied Medical Chemistry Department, Medical Research Institute, Alexandria University, Alexandria, Egypt E-mail : prof_abdelmohsenma@yahoo.com.
authors.forename: Mohamed Ahmed
authors.initials: MA
authors.lastname: Abdel-Mohsen
authors.forename: Omiama Ali
authors.initials: OA
authors.lastname: Ahmed
authors.forename: Yasser Mostafa
authors.initials: YM
authors.lastname: El-Kerm
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D001343:Autophagy / Q000187:drug effects* / Q000235:genetics; D019313:BRCA1 Protein / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D003520:Cyclophosphamide / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D004534:Egypt; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D009154:Mutation / Q000235:genetics*; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis
chemical_list: D051017:Apoptosis Regulatory Proteins; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D014408:Biomarkers, Tumor; D004317:Doxorubicin; D003520:Cyclophosphamide; D005472:Fluorouracil