Methylation of breast cancer susceptibility gene 1 (BRCA1) predicts recurrence in patients with curatively resected stage I non-small cell lung cancer

Cancer. 2013 Feb 15;119(4):792-8. doi: 10.1002/cncr.27754. Epub 2013 Jan 18.

Abstract

Background: Even after early detection and curative resection of early stage non-small cell lung cancer (NSCLC), a significant fraction of patients develop recurrent disease. Molecular biomarkers that can predict the risk of recurrence thus need to be identified to improve clinical outcomes.

Methods: Using the methylation-specific polymerase chain reaction assay, promoter methylation of the breast cancer susceptibility gene 1 (BRCA1) was assessed in cancer tissues from 70 patients with curatively resected stage I NSCLC. The clinical relevance of BRCA1 methylation status was evaluated in terms of outcome of the disease.

Results: Methylation of the BRCA1 promoter was detected in 13 of 70 patients (18.6%). Multiple logistic regression analysis revealed that BRCA1 methylation was an independent risk factor for recurrence (P = .0197) and that patients with BRCA1 methylation demonstrated significantly poorer recurrence-free survival compared to those without (P = .0139). Cox's proportional hazard regression analysis revealed that BRCA1 methylation was an independent risk factor for recurrence-free survival (P = .0155).

Conclusions: Methylated BRCA1 can be a potential biomarker that predicts the prognosis after curative resection of stage I NSCLC. Considering that BRCA1 plays a role in chemotherapy-induced apoptosis, it is plausible that identification of methylated BRCA1 could provide information that is clinically relevant to tailored adjuvant therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • BRCA1 Protein / genetics*
  • BRCA1 Protein / metabolism
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / surgery
  • DNA Methylation*
  • Disease-Free Survival
  • Female
  • Humans
  • Logistic Models
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / surgery
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / genetics
  • Polymerase Chain Reaction
  • Predictive Value of Tests
  • Prognosis
  • Promoter Regions, Genetic
  • Treatment Outcome

Substances

  • BRCA1 Protein