title: Evaluation of single nucleotide polymorphisms (SNPs) in the p53 binding protein 1 (TP53BP1) gene in breast cancer patients treated with breast-conserving surgery and whole-breast irradiation (BCS + RT).
abstract: OBJECTIVE
  TP53BP1 is a key component of radiation-induced deoxyribonucleic acid damage repair. The purpose of this study was to evaluate the significance of a known common single nucleotide polymorphism in this gene (rs560191) in patients treated with breast-conserving surgery and whole-breast irradiation (BCS + RT).
  
  
  METHODS
  The population consisted of 176 premenopausal women treated with BCS + RT (median follow-up, 12 years). Genomic deoxyribonucleic acid was processed by use of TaqMan assays. Each allele for rs560191 was either C or G, so each patient was therefore classified as CC, CG, or GG. Patients were grouped as GG if they were homozygous for the variant G allele or CC-CG if they carried at least one copy of the common C allele (CC or CG).
  
  
  RESULTS
  Of the 176 women, 124 (71%) were CC-CG and 52 (29%) were GG. The mean age was 44 years for GG vs. 38 years for CC-CG (p < 0.001). GG was more common in African-American women than white women (69% vs. 13%, p < 0.001) and more commonly estrogen receptor negative (70% vs. 49%, p = 0.02). There were no significant correlations of rs560191 with other critical variables. Despite the fact that GG patients were older, the 10-year rate of local relapses was higher (22% for GG vs. 12% for CC-CG, p = 0.04).
  
  
  CONCLUSIONS
  This novel avenue of investigation of polymorphisms in radiation repair/response genes in patients treated with BCS + RT suggests a correlation to local relapse. Additional evaluation is needed to assess the biological and functional significance of these single nucleotide polymorphisms, and larger confirmatory validation studies will be required to determine the clinical implications.
authors.affiliation: Robert Wood Johnson Medical School-Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ 08901, USA. hafftybg@umdnj.edu
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Haffty
authors.forename: Sharad
authors.initials: S
authors.lastname: Goyal
authors.forename: Diptee
authors.initials: D
authors.lastname: Kulkarni
authors.forename: Camille
authors.initials: C
authors.lastname: Green
authors.forename: Alexi
authors.initials: A
authors.lastname: Vazquez
authors.forename: Devora
authors.initials: D
authors.lastname: Schiff
authors.forename: Meena S
authors.initials: MS
authors.lastname: Moran
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Yang
authors.forename: Shridar
authors.initials: S
authors.lastname: Ganesan
authors.forename: Kim M
authors.initials: KM
authors.lastname: Hirsfield
mesh_terms: D000328:Adult; D000483:Alleles; D001943:Breast Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000532:radiotherapy / Q000601:surgery; D003131:Combined Modality Therapy / Q000379:methods; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D015810:Linkage Disequilibrium; D015412:Mastectomy, Segmental; D009363:Neoplasm Proteins / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017697:Premenopause; D000071857:Tumor Suppressor p53-Binding Protein 1
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; C498301:TP53BP1 protein, human; D000071857:Tumor Suppressor p53-Binding Protein 1