Abstract
Triple-negative breast cancer (TNBC) refers to one aggressive histological subtype of breast cancer with high heterogeneity and poor prognosis after standard therapy. Lack of clearly established molecular mechanism driving TNBC progression makes personalized therapy more difficult. Thus, identification of genetic variants associated with TNBC prognosis will show clinic significance for individualized treatments. Our study is aimed to evaluate the prognostic value of the genome wide association study (GWAS)-identified CHST9 rs1436904 and AQP4 rs527616 genetic variants in our established early-stage TNBC sample database. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). CHST9 rs1436904G allele was significantly associated with decreased disease-free survival time (DFS) (8.5 months shorter in GG genotype carriers compared to TT genotype carriers, HR = 1.70, 95% CI = 1.03–2.81, P = 0.038). Stratified analyses showed an increased risk of cancer progression in CHST9 rs1436904G allele carriers harboring larger tumor (tumor size > 2 cm), without lymph-node metastasis, being premenopausal at diagnosis or with vascular invasion (P = 0.032, 0.017, 0.008 or 0.003). Our findings demonstrate that the GWAS-identified 18q11.2 CHST9 rs1436904 polymorphism significantly contributes to prognosis of early-stage TNBC, suggesting its clinical potential in the screening of high-risk TNBC patients for recurrence and the possibility of patient-tailored therapeutic decisions.
Highlights
Breast cancer is one of the most common malignancies worldwide, with an estimated 255,180 new cases and 41,070 deaths in the United States in 20171
That genetic variants on top of conventional risk factors did improve the risk prediction of breast cancer in Chinese women[25], but not clear enough to declare whether CHST9 rs1436904 and AQP4 rs527616 affect prognosis of Triple-negative breast cancer (TNBC)
We found that the CHST9 rs1436904 polymorphism might be a potential prognostic biomarker for early-stage TNBC, especially in the patients harboring larger tumor, without lymph-node metastasis, being premenopausal at diagnosis or with vascular invasion
Summary
A total of 381 TNBC patients were recruited between January 2008 and December 2015 at Cancer Hospital, Chinese Academy of Medical Sciences (Beijing, China). These patients were followed until May 6, 2016 in order to collect data on clinicopathological characteristics, treatments, and vital status, such as recurrence and death. The multivariate Cox proportional hazards model was applied to estimate effects of prognostic factors on DFS, using proverbial clinical factors, including age of onset, body mass index (BMI), tumor size, lymph-node metastasis, histological type, histological grade, menopausal status, vascular invasion, breast or ovarian cancer history, surgical method, taxane/anthracycline-based chemotherapy and radiotherapy, where it was appropriate. All statistical procedures were conducted using SPSS software (version 16.0)
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