title: XRCC1 polymorphisms and breast cancer risk from the New York Site of the Breast Cancer Family Registry: A family-based case-control study.
abstract: BACKGROUND
  XRCC1 is a scaffold protein involved in the early and late stages of Base Excision Repair (BER). Three DNA polymorphisms occur in XRCC1, resulting in non-synonymous amino acid changes, which could alter the binding or regulatory activities of XRCC1.
  
  
  METHODS
  We used a family-based case-control study design to evaluate the association between XRCC1 polymorphisms and breast cancer risk. Participants were breast cancer cases and their unaffected sisters enrolled in the New York Site of the Breast Cancer Family Registry. Conditional logistic regression was used to assess associations between genotype and breast cancer. XRCC1 mRNA levels and DNA nicking activity were measured in lymphoblastoid cell lines from unaffected sisters to determine whether the XRCC1 R399Q polymorphism has a functional effect on expression or protein activity.
  
  
  RESULTS
  XRCC1 194W was associated with a non-significant increase in breast cancer, while XRCC1 280H and XRCC1 399Q were associated with a non-significant decrease in breast cancer. We found a significant increase in XRCC1 expression in 399Q/Q lymphoblastoid cell lines from unaffected sisters (n=28, P=0.03). An increase in median nicking activity was not statistically significant.
  
  
  CONCLUSIONS
  Our results suggest that XRCC1 399Q may alter mRNA expression and DNA repair phenotype, although the main effects of the genotype were not significantly associated with familial cancer risk. Additional research on the regulation of XRCC1 expression will contribute to an understanding of how this polymorphism may impact disease risk.
authors.affiliation: Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Zipprich
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Terry
authors.forename: Paul
authors.initials: P
authors.lastname: Brandt-Rauf
authors.forename: Greg A
authors.initials: GA
authors.lastname: Freyer
authors.forename: Yuyan
authors.initials: Y
authors.lastname: Liao
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Agrawal
authors.forename: Irina
authors.initials: I
authors.lastname: Gurvich
authors.forename: Ruby
authors.initials: R
authors.lastname: Senie
authors.forename: Regina M
authors.initials: RM
authors.lastname: Santella