title: The relationship between eight GWAS-identified single-nucleotide polymorphisms and primary breast cancer outcomes.
abstract: BACKGROUND
  Several single-nucleotide polymorphisms (SNPs) associated with breast cancer risk have been identified through genome-wide association studies (GWAS). We investigated whether eight risk SNPs identified in GWAS were associated with breast cancer disease-free survival (DFS) and overall survival (OS) rates.
  
  
  METHODS
  A cohort of 739 white women with early-stage breast cancer was genotyped for eight GWAS-identified SNPs (rs2981582, rs1219648 [FGFR2], rs3803662, rs12443621, rs8051542 [TOX3], rs999737 [RAD51L1], rs6504950 [17q23], and rs4973768 [3p24]). Relationships between SNPs and breast cancer outcomes were evaluated using Cox proportional hazard regression models. The cumulative effects of SNPs on breast cancer outcomes were assessed by computing the number of at-risk genotypes.
  
  
  RESULTS
  At a median follow-up of 121 months (range: 188-231 months) for survivors, 237 deaths (32%) and 186 breast cancer events (25%) were identified among the 739 patients. After adjusting for age, clinical stage, and treatment, rs12443621 (16q12; p = .03) and rs6504950 (17q23; p = .008) were prognostic for OS but not DFS. A higher risk for death was also found in the multivariable analysis of patients harboring three or four at-risk genotypes of the GWAS SNPs compared to patients carrying two or less at-risk genotypes (hazard ratio: 1.60, 95% confidence interval: 1.23-2.24; p = .0008).
  
  
  CONCLUSIONS
  The study results suggest that previously identified breast cancer risk susceptibility loci, rs12443621 (16q12) and rs6504950 (17q23), may influence breast cancer prognosis or comorbid conditions associated with overall survival. The precise molecular mechanisms through which these risk SNPs, as well as others that were not included in the analysis, influence clinical outcomes remain to be determined.
authors: Department of Medical Oncology, Mercy Cancer Center, Ardmore, Oklahoma, USA.
authors: Soley
authors: S
authors: Bayraktar
authors: Patricia A
authors: PA
authors: Thompson
authors: Suk-Young
authors: SY
authors: Yoo
authors: Kim-anh
authors: KA
authors: Do
authors: Aysegul A
authors: AA
authors: Sahin
authors: Banu K
authors: BK
authors: Arun
authors: Melissa L
authors: ML
authors: Bondy
authors: Abenaa M
authors: AM
authors: Brewster
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D018572:Disease-Free Survival; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016016:Proportional Hazards Models; D012307:Risk Factors; D016896:Treatment Outcome; D044465:White People / Q000235:genetics
keywords: 17q23; Breast cancer; Prognosis; Single-nucleotide polymorphisms; TNRC9
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