AHRR (cg05575921) methylation extent of leukocyte DNA and lung cancer survival

PLoS One. 2019 Feb 7;14(2):e0211745. doi: 10.1371/journal.pone.0211745. eCollection 2019.

Abstract

Background: Prior studies have shown that AHRR (cg05575921) hypomethylation may be a marker of smoking, lung cancer risk and potentially lung cancer survival (in some lung cancer subtypes). It is unknown if AHRR (cg05575921) hypomethylation is associated with reduced survival among lung cancer patients.

Methods: In bisulfite treated leukocyte DNA from 465 lung cancer patients from the Copenhagen prospective lung cancer study, we measured AHRR (cg05575921) methylation. 380 died during max follow-up of 4.4 years. Cox proportional hazard models were used to analyze survival as a function of AHRR (cg05575921) methylation.

Results: We observed the expected inverse correlation between cumulative smoking and AHRR methylation, as methylation (%) decreased (Coefficient -0.03; 95% confidence interval, -0.04- -0.02, p = 8.6x10-15) for every pack-year. Cumulative smoking > 60 pack-years was associated with reduced survival (hazard ratio and 95% confidence interval 1.48; 1.05-2.09), however, AHRR (cg05575921) methylation was not associated with survival when adjusted for sex, body mass index, smoking status, ethnicity, performance status, TNM Classification, and histology type of lung cancer.

Conclusion: AHRR (cg05575921) methylation is linked to smoking but does not provide independent prognostic information in lung cancer patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Basic Helix-Loop-Helix Transcription Factors / blood*
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / genetics
  • DNA Methylation*
  • DNA, Neoplasm / blood*
  • DNA, Neoplasm / genetics
  • Disease-Free Survival
  • Female
  • Humans
  • Leukocytes / metabolism*
  • Leukocytes / pathology
  • Lung Neoplasms / blood*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / mortality*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Proteins / blood*
  • Neoplasm Proteins / genetics
  • Prospective Studies
  • Repressor Proteins / blood*
  • Repressor Proteins / genetics
  • Smoking / blood
  • Smoking / genetics
  • Smoking / mortality
  • Survival Rate

Substances

  • AHRR protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • Biomarkers, Tumor
  • DNA, Neoplasm
  • Neoplasm Proteins
  • Repressor Proteins

Grants and funding

The salary of Katja Kemp Jacobsen was funded by a Post doc grant from Lundbeck Foundation. This funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.