CHST9 rs1436904 genetic variant contributes to prognosis of triple-negative breast cancer

Sci Rep. 2017 Sep 18;7(1):11802. doi: 10.1038/s41598-017-12306-6.

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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Disease-Free Survival
  • Female
  • Genome-Wide Association Study
  • Genotype*
  • Humans
  • Middle Aged
  • Neoplasm Recurrence, Local* / enzymology
  • Neoplasm Recurrence, Local* / genetics
  • Neoplasm Recurrence, Local* / mortality
  • Polymorphism, Genetic*
  • Sulfotransferases / genetics*
  • Survival Rate
  • Triple Negative Breast Neoplasms* / enzymology
  • Triple Negative Breast Neoplasms* / genetics
  • Triple Negative Breast Neoplasms* / mortality

Substances

  • CHST9 protein, human
  • Sulfotransferases