TY - JOUR
T1 - The relationship between eight GWAS-identified single-nucleotide polymorphisms and primary breast cancer outcomes
AU - Bayraktar, Soley
AU - Thompson, Patricia A.
AU - Yoo, Suk Young
AU - Do, Kim Anh
AU - Sahin, Aysegul A.
AU - Arun, Banu K.
AU - Bondy, Melissa L.
AU - Brewster, Abenaa M.
PY - 2013/5
Y1 - 2013/5
N2 - Background. Several single-nucleotide polymorphisms (SNPs) associated with breast cancer risk have been identified through genome-wide association studies (GWAS).Weinvestigated whether eight risk SNPs identified inGWASwere associated with breast cancer disease-free survival (DFS) and overall survival (OS) rates. Patients and Methods. A cohort of 739 white women with early-stage breast cancer was genotyped for eight GWASidentified 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 atrisk genotypes (hazard ratio: 1.60, 95% confidence interval: 1.23-2.24; p=.0008). Conclusion. 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.
AB - Background. Several single-nucleotide polymorphisms (SNPs) associated with breast cancer risk have been identified through genome-wide association studies (GWAS).Weinvestigated whether eight risk SNPs identified inGWASwere associated with breast cancer disease-free survival (DFS) and overall survival (OS) rates. Patients and Methods. A cohort of 739 white women with early-stage breast cancer was genotyped for eight GWASidentified 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 atrisk genotypes (hazard ratio: 1.60, 95% confidence interval: 1.23-2.24; p=.0008). Conclusion. 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.
KW - 17q23
KW - Breast cancer
KW - Prognosis
KW - Single-nucleotide polymorphisms
KW - TNRC9
UR - http://www.scopus.com/inward/record.url?scp=84878165328&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84878165328&partnerID=8YFLogxK
U2 - 10.1634/theoncologist.2012-0419
DO - 10.1634/theoncologist.2012-0419
M3 - Article
C2 - 23635555
AN - SCOPUS:84878165328
SN - 1083-7159
VL - 18
SP - 493
EP - 500
JO - Oncologist
JF - Oncologist
IS - 5
ER -