Abstract
BackgroundPrior 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.MethodsIn 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.ResultsWe 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.ConclusionAHRR (cg05575921) methylation is linked to smoking but does not provide independent prognostic information in lung cancer patients.
Highlights
Lung cancer is the leading cause of cancer-related death worldwide [1]
Prior studies have shown that aryl-hydrocarbon receptor repressor (AHRR) hypomethylation may be a marker of smoking, lung cancer risk and potentially lung cancer survival
Cumulative smoking > 60 pack-years was associated with reduced survival, AHRR 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
Summary
Lung cancer is the leading cause of cancer-related death worldwide [1]. The overall 5-year survival of lung cancer patients remains below 20% [2,3], mainly because tumors are diagnosed at late stages [4]. AHRR (cg05575921) hypomethylation of leukocyte DNA is associated with both former and current smoking status, daily cigarette consumption, cumulative smoking and smoking duration in both former and current smokers, and time since quitting in former smokers [19]. This suggests that blood based AHRR (cg05575921) methylation extent can be used as an objective measure of long-term smoking exposure. 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
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