title: A role for XRCC2 gene polymorphisms in breast cancer risk and survival.
abstract: BACKGROUND
  The XRCC2 gene is a key mediator in the homologous recombination repair of DNA double strand breaks. It is hypothesised that inherited variants in the XRCC2 gene might also affect susceptibility to, and survival from, breast cancer.
  
  
  METHODS
  The study genotyped 12 XRCC2 tagging single nucleotide polymorphisms (SNPs) in 1131 breast cancer cases and 1148 controls from the Sheffield Breast Cancer Study (SBCS), and examined their associations with breast cancer risk and survival by estimating ORs and HRs, and their corresponding 95% CIs. Positive findings were further investigated in 860 cases and 869 controls from the Utah Breast Cancer Study (UBCS) and jointly analysed together with available published data for breast cancer risk. The survival findings were further confirmed in studies (8074 cases) from the Breast Cancer Association Consortium (BCAC).
  
  
  RESULTS
  The most significant association with breast cancer risk in the SBCS dataset was the XRCC2 rs3218408 SNP (recessive model p=2.3×10(-4), minor allele frequency (MAF)=0.23). This SNP yielded an OR(rec) of 1.64 (95% CI 1.25 to 2.16) in a two-site analysis of SBCS and UBCS, and a meta-OR(rec) of 1.33 (95% CI 1.12 to 1.57) when all published data were included. This SNP may mark a rare risk haplotype carried by two in 1000 of the control population. Furthermore, the XRCC2 coding R188H SNP (rs3218536, MAF=0.08) was significantly associated with poor survival, with an increased per-allele HR of 1.58 (95% CI 1.01 to 2.49) in a multivariate analysis. This effect was still evident in a pooled meta-analysis of 8781 breast cancer patients from the BCAC (HR 1.19, 95% CI 1.05 to 1.36; p=0.01).
  
  
  CONCLUSIONS
  These findings suggest that XRCC2 SNPs may influence breast cancer risk and survival.
authors.affiliation: Institute for Cancer Studies, Department of Oncology, University of Sheffield,Sheffield, UK.
authors.forename: Wei-Yu
authors.initials: WY
authors.lastname: Lin
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Camp
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Cannon-Albright
authors.forename: Kristina
authors.initials: K
authors.lastname: Allen-Brady
authors.forename: Sabapathy
authors.initials: S
authors.lastname: Balasubramanian
authors.forename: Malcolm W R
authors.initials: MW
authors.lastname: Reed
authors.forename: John L
authors.initials: JL
authors.lastname: Hopper
authors.forename: Carmel
authors.initials: C
authors.lastname: Apicella
authors.forename: Graham G
authors.initials: GG
authors.lastname: Giles
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Southey
authors.forename: Roger L
authors.initials: RL
authors.lastname: Milne
authors.forename: Jose I
authors.initials: JI
authors.lastname: Arias-Pérez
authors.forename: Primitiva
authors.initials: P
authors.lastname: Menéndez-Rodríguez
authors.forename: Javier
authors.initials: J
authors.lastname: Benítez
authors.forename: Magdalena
authors.initials: M
authors.lastname: Grundmann
authors.forename: Natalia
authors.initials: N
authors.lastname: Dubrowinskaja
authors.forename: Tjoung-Won
authors.initials: TW
authors.lastname: Park-Simon
authors.forename: Thilo
authors.initials: T
authors.lastname: Dörk
authors.forename: Montserrat
authors.initials: M
authors.lastname: Garcia-Closas
authors.forename: Jonine
authors.initials: J
authors.lastname: Figueroa
authors.forename: Mark
authors.initials: M
authors.lastname: Sherman
authors.forename: Jolanta
authors.initials: J
authors.lastname: Lissowska
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Easton
authors.forename: Alison M
authors.initials: AM
authors.lastname: Dunning
authors.forename: Preetha
authors.initials: P
authors.lastname: Rajaraman
authors.forename: Alice J
authors.initials: AJ
authors.lastname: Sigurdson
authors.forename: Michele M
authors.initials: MM
authors.lastname: Doody
authors.forename: Martha S
authors.initials: MS
authors.lastname: Linet
authors.forename: Paul D
authors.initials: PD
authors.lastname: Pharoah
authors.forename: Marjanka K
authors.initials: MK
authors.lastname: Schmidt
authors.forename: Angela
authors.initials: A
authors.lastname: Cox
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality*; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012306:Risk; D016019:Survival Analysis
chemical_list: D004268:DNA-Binding Proteins; C113187:XRCC2 protein, human