title: The RAD51 135G>C polymorphism is related to the effect of adjuvant therapy in early breast cancer.
abstract: OBJECTIVE
  RAD51, a central player in the response to DNA damage, has been suspected to contribute to tumour resistance to therapy. A single-nucleotide polymorphism, RAD51 135G>C, in the untranslated region of the RAD51 gene elevates breast cancer risk among BRCA2 carriers. In this study, it was investigated whether this polymorphism is related to prognosis of breast cancer and RAD51 protein expression and whether it is indicative of resistance to radiotherapy or cyclophosphamide/methotrexate/5-fluorouracil (CMF) chemotherapy.
  
  
  METHODS
  We genotyped 306 patients with early breast cancer, who were randomised to receive post-operative radiotherapy or CMF chemotherapy, for the RAD51 135G>C polymorphism. RAD51 protein expression was evaluated with immunohistochemistry.
  
  
  RESULTS
  15.4 % of the patients had at least one C-allele (three were C homozygotes). There was no correlation between genotype and protein expression. Patients who were G homozygotes benefitted from radiotherapy with decreased risk of local recurrences (RR = 0.32, 95 % C.I. 0.16-0.64, p = 0.001). CMF chemotherapy reduced the risk of distant recurrence for patients carrying at least one C-allele (RR = 0.29, 95 % C.I. 0.10-0.88, p = 0.03), whereas G homozygotes had no benefit from chemotherapy. There was a significant interaction between chemotherapy and genotype (p = 0.02).
  
  
  CONCLUSIONS
  The results suggest that the RAD51 135G>C polymorphism predicts CMF chemotherapy effect in early breast cancer.
authors.affiliation: Division of Surgery and Clinical Oncology, Department of Clinical and Experimental Medicine, Linköping University, 581 85, Linköping, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Söderlund Leifler
authors.forename: A
authors.initials: A
authors.lastname: Asklid
authors.forename: T
authors.initials: T
authors.lastname: Fornander
authors.forename: M
authors.initials: M
authors.lastname: Stenmark Askmalm
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D003596:Cytosine; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006147:Guanine; D006801:Humans; D015412:Mastectomy, Segmental; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D016133:Polymerase Chain Reaction / Q000379:methods; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011379:Prognosis; D051135:Rad51 Recombinase / Q000235:genetics*; D018714:Radiotherapy, Adjuvant; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome
chemical_list: D006147:Guanine; D003596:Cytosine; D003520:Cyclophosphamide; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; D005472:Fluorouracil; D008727:Methotrexate