ANO7 rs77559646 Is Associated With First-line Docetaxel Treatment Response in Metastatic Castration-resistant Prostate Cancer

Anticancer Res. 2019 Oct;39(10):5353-5359. doi: 10.21873/anticanres.13728.

Abstract

Background: Identification of genetic prognostic biomarkers, such as germline variants, are urgently needed to choose optimal treatment for metastatic castration-resistant prostate cancer (mCRPC).

Patients and methods: The prognostic value of anoctamin 7 (ANO7) rs77559646 on docetaxel response was tested in a prospective PROSTY randomized trial and a retrospective Auria Biobank set. The variant rs77559646 was genotyped and its association with progression-free survival (PFS) and overall survival (OS) was tested.

Results: In comparison with the non-carriers, the variant carriers had longer PFS (p=0.005) and OS (p=0.003) in the PROSTY cohort. In the retrospective cohort, there was a borderline association with PFS (p=0.09), but not in OS (p=0.9). In both cohorts, Cox regression multivariate models revealed that rs77559646 was an independent prognostic factor for favourable PFS.

Conclusion: The rs77559646 was shown to be a prognostic germline biomarker for better response to docetaxel treatments. To our knowledge, this is the first time that a non-coding germline variant has been associated with chemotherapy of mCRPC.

Keywords: ANO7; CRPC; docetaxel; prostate cancer.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Anoctamins / genetics*
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / genetics
  • Cohort Studies
  • Docetaxel / therapeutic use*
  • Genetic Variation / genetics*
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Progression-Free Survival
  • Proportional Hazards Models
  • Prospective Studies
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Prostatic Neoplasms, Castration-Resistant / genetics*
  • Prostatic Neoplasms, Castration-Resistant / pathology
  • Retrospective Studies

Substances

  • ANO7 protein, human
  • Anoctamins
  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Docetaxel